fbpx

Rheumatoid arthritis

Updated : July 4, 2024





Background

Rheumatoid arthritis is an inflammatory condition of the joints caused by the immune system attacking its own tissues. It can affect any joint but is common in the wrist and fingers. The disease is highly symmetrical; that means if one hand has it, the other probably will too. Moreover, it progresses from small joints to large ones as time goes on. Swollen and painful joints result from a thickened synovium. 

Joints contain the end of a bone called cartilage. This cushion supports against shock when we move. Eventually, the cartilage is worn due to the disease’s inflammation which is the consequence of RA. Consequently, wear and tear of cartilage makes both pieces of the joint or parts of the joints rub against each other and destroy them. This makes to the weakened bones. 

Epidemiology

Rheumatoid arthritis (RA) is more common in the United States and other Western countries of northern Europe where it occurs with about 40 cases per 100,000 people annually. According to epidemiologic information, the lifetime risk of developing this disease is 3.6% for women and 1.7% for men. Furthermore, it has been noted that those between 65 to 80 years have shown maximum susceptibility to rheumatism. 

Anatomy

Pathophysiology

Patients diagnosed with rheumatoid arthritis (RA) tend to produce antibodies against proteins with certain features. The post-translational modification of arginyl residues by peptidyl arginine deaminases leads to the production of citrulline, an amino acid. The antibodies are called anti-citrullinated protein antibodies (ACPAs) and can be of IgA, IgG or IgM type.  

When these proteins are bound by antibodies, they trigger complement system activation. Antibodies in RA which react to them are called seropositive RA. It is believed that repetitive provocation of innate immunity marks environment-induced RA. One example is smoking which activates alveolar macrophages to release peptidyl arginine deiminase hence converting arginine to citrulline in the respiratory tract. 

During this process a neoantigen is formed which produces an immune reaction, what eventually leads to antibodies development in the body which are specific against citrullinated proteins. Furthermore, RA symptoms are closely associated with production of antibodies reactive towards post-translationally-modified proteins known as anti-carbamylated protein (anti-CarP) antibodies. Homocitrulline is a result of lysine transformation by cyanide as it causes carbamylation to take place. 

Homocitrulline shares a common molecular structure with citrulline but anti-CarP antibodies are different and have been associated with RA in both ACPA-positive and ACPA-negative persons. In about 40% of RA patients, anti-acetylated protein antibodies were recently described mostly in seropositive patients. RA can be linked to microbiome dysbiosis due to the acetylation process which forms this disease. 

Etiology

Rheumatoid arthritis (RA) is believed to be due to an interaction between the patient’s environment and genotype. The precise cause of rheumatoid arthritis remains unclear. The levels of an increasing risk for RA are related to the genetic susceptibility which is indicated by the heritability for seropositive and seronegative RA in the range of 40%-65%. RA risk is higher as alleles HLA-DRB1*10, HLA-DRB104 and HLA-DRB101 are more frequent. 

There is a common epitope shared by these HLA_DRB1 alleles within the third hypervariable region of their DRB1 chain made up of a sequence of five conserved amino acids that has been linked to a high chance of developing RA. Other genes, including IL-10 and STAT-4 that are believed to play a part in determining who gets RA also show variability. 

Discovery of single nucleotide polymorphisms (SNPs) in genes such as PTPN2, MIR146A, and PSORS1C1 is related with RA. Additionally, alteration of the gut microbiome structure and function has been identified with RA. Gut microbiota dysbiosis due to less diversity as compared to healthy individuals is one of the main characteristics of RA in patients with this condition. 

Genetics

Prognostic Factors

Rheumatoid arthritis is a constant illness with no established cure yet. Each patient has multiple episodes that end up being bad including higher disability levels and sometimes even death occurring. Early detection within the first 6 months of showing symptoms after the onset of the disease can lead to increased ability to work and decreased severity of illness as indicated by number of swollen or tender joints. 

Be that as it may, the rate of death is approximately equal for individuals who receive early treatment as well as those who receive late treatment, it is much better than that for people who do not get any treatment them at all six months after symptoms appear. 

Clinical History

RA refers to long-term spherical arthritis (synovitis), mostly in the feet and hands in an identical way. This is characterized by hand or foot symmetric polyarthritis in most of the cases though any joint which possess synovial membrane may get involved. Still, RA can present variably over time, however it usually ends up with progressive joint destruction resulting into deformity as well as reduction of the ability to carry out daily activities. Rheumatoid arthritis (RA) may also affect organs like skin, heart, lungs and eyes not only joints. 

Juvenile idiopathic arthritis, which is sometimes known as juvenile rheumatoid arthritis, is the most common kind of childhood arthritis. The immunogenic alleles, clinical course, and functional result of the JIA in the majority of patients are unlike adult-onset RA. 

Patients who have RA may have problems while performing their daily routines such as putting on clothes; they might not also be able to stand, walk around the house or take care of themselves particularly if they cannot use their hands freely; sometimes these patients may even lose strength and face some other joint related problems like arthritis as well as feel tired. 

RA is the way it typically sets about its course with the later occurrence of overt joint inflammation or swelling after earlier systemic features like fever, malaise, arthralgias, and weakness. A tiny fraction (about 10 percent) has an explosive beginning marked by synovitis and extra-articular signs. Although rare, spontaneous recovery can happen, particularly within the first six months. 

Physical Examination

It is important to examine the following: 

Swelling 

Tenderness 

Deformity 

Stiffness 

Limitation of motion 

Rheumatoid nodules 

Pain during movement 

Extra-articular manifestations 

In RA, joint involvement is featured and distinct. Usually, there is symmetric distribution of relatively involved small joints of hands and feet. The commonly affected joints are the metatarsophalangeal (MTP), knee, wrist, shoulder, metacarpophalangeal (MCP), proximal interphalangeal (PIP), ankle, hip, cervical spine, elbow and temporomandibular joints in this order. 

Inflammation is seen in the affected joints, and they are also swollen, tender to touch, warm, and they have limited motion range (ROM). Muscle atrophy in the hands between bones can appear as one characteristic of early condition. It is possible for joints and tendons to become destroyed which can cause problems such as ulnar deviation’ boutonniere’ swan neck deformities (flexion contractures of MCP and DIP joints) hammer toes; sometimes even locking of joints through bony outgrowths (ankylosis). 

Other common manifestations include: 

Tenosynovitis 

Periarticular osteoporosis 

Carpel tunnel syndrome 

Generalized osteoporosis 

Most patients suffer muscle atrophy secondary to joint inflammation. 

Examination of upper extremities 

Fingers: Synovitis causes deformity in the PIP joint, causing lateral bands to become flexors. Hyperextension of the DIP joint occurs as tendons shorten. Swan-neck deformity describes hyperextension at the PIP joint with DIP joint flexion. 

Metacarpophalangeal joints: Volar subluxation and ulnar deviation are common deformities that affect palmar skeletal arches and finger stability at metacarpophalangeal (MCP) joints. Ulnar deviation occurs when synovitis weakens the volar plate and collateral ligaments, allowing the flexor tendon to dislocate volarward and ulnarward. The supporting structures of extensor tendons may also become attenuated or destroyed. If the extensor tendon subluxation moves beyond the MCP joint, it acts as a flexor, further limiting finger extension. 

Wrists: Wrist deformities can include disruption of the radioulnar joint, ulnarly translocated lunate, zigzag deformity and rotational deformities.
Rotational deformities shorten carpal height and cause loss of cartilage. Dorsal subluxation of the ulna may lead to rupture of the extensor tendons, particularly in the presence of tenosynovitis. Impingement neuropathy may occur due to synovitis around flexor tendons resulting in decreased sensation, weakness and thenar muscle atrophy. Entrapment of the ulnar nerve at the wrist can cause reduced sensation and interosseous muscle weakness, especially if tenosynovitis is present.  

Elbow: This can often lead to elbow synovitis, contraction, olecranon bursitis, and rheumatoid nodules in the bursa and ulna with flexion deformities being common. 

Shoulders: It often impacts the shoulders causing tenderness, nocturnal pain and limited mobility. Symptoms include rotator cuff degeneration, glenoid damage, frozen shoulder syndrome and rare aromioclavicular arthritis which is less disabling than the other RA manifestations. 

Examination of lower extremities 

Feet and ankles: It is unusual for the ankle joint to become inflamed without affecting the midfoot or metatarsophalangeal (MTP) joints. Weight-bearing and chronic synovitis may lead to structural changes that eventually result in subluxation of the subtalar joint and loss of the foot arch contour. Over time, the MTP joints may develop deformities such as hallux valgus, hammer toes, and calluses. Pain may occur during weight-bearing activities when the second and third metatarsal heads become the major weight-bearing surfaces. 

Knees: It causes knee effusions and synovial thickening, leading to muscle atrophy and instability. Progressive cartilage loss and ligament weakening can cause deformities like genu valgus or varus, increasing energy expenditure during standing or walking. 

Hips: Involvement of hip is common in rheumatoid arthritis (RA), but symptoms may not be immediately apparent due to their deep location. Signs include limited motion or pain during movement and weight-bearing. Abnormalities can be detected using the Patrick maneuver and the Thomas test, which may indicate contracture. 

Cervical spine: Involvement of cervical spine in rheumatoid arthritis (RA) can lead to serious neurologic consequences, including neck pain and occipital headaches. Most patients have had RA for over 10 years and experience stiffness throughout their neck’s range of motion. Neurological involvement can range from radicular pain to spinal cord lesions, resulting in weakness, sphincter dysfunction, sensory deficits, and abnormal reflexes. Cervical myelopathy typically develops gradually and may not correlate with neck pain. Patients requiring intubation or neck manipulation should undergo a thorough cervical spine evaluation. 

Pain during movement, tenderness and stiffness: Rheumatoid arthritis (RA) is assessed through physical examination, focusing on joint motion limitations. Stiffness is usually caused by articular surface damage or soft tissue contractures. Heat can alleviate stiffness, but active exercise is most effective. Joint tenderness is elicited through direct palpation, with pain-sensitive structures like the enlarged synovial membrane, periarticular ligaments, and supporting structures. Pain during joint motion is often used to indicate tenderness in joints with difficulty in palpation due to overlying muscles and tissues.  

Deformity, limitation of motion, and swelling: RA is a condition in which the synovial membrane becomes inflamed, causing swelling in small joints like those found in the hands and feet. This swelling can be due to joint effusions that may result in a Baker cyst being formed, which can cause severe pain if it ruptures. As time goes on, joint deformities develop as a result of damage done to supporting structures and articular by the inflammatory process. The hands and feet’s small joints are mostly affected by this process with more than 10% of all patients suffering from RA having deformities within their hand joints within two years of being diagnosed with the disease. If supporting structures become disrupted then there can be instability at these joints too; however, such movement may also be restricted significantly through mechanical factors because subluxations as well as deformities throughout different parts of one joint greatly reduce its range of motion. 

Extra-articular manifestations: RA is a systemic disease-causing generalized malaise and fatigue, with some more common in men, but similar prevalence across genders. 

Rheumatoid nodules: They occur in 25% of RA patients  but very rarely in the first year. They emerge on extensor surfaces or virtually on any part of the body that is affected by intense mechanical irritation. Elbow joint, heel, proximal ulna, occiput, ischial tuberosities, and subcutaneous tissues are commonly affected sites. 

RA also affects various organ systems like: 

  • Cardiac 
  • Renal 
  • Cutaneous 
  • Vascular 
  • Neurologic 
  • Ocular 
  • Gastrointestinal (GI) 
  • Hematologic 
  • Ocular 
  • Differential diagnoses 
  • Lyme disease 
  • Osteoarthritis 
  • Relapsing polychondritis 
  • Psoriatric arthritis 
  • Sjogren syndrome 
  • Paraneoplastic syndrome 
  • Fibromyalgia 
  • Lyme disease 
  • SLE 
  • Relapsing polychondritis 

Age group

Associated comorbidity

Pain and joint disability in day to day life 

Anemia 

Gastrointestinal issues 

Osteoporosis 

Increased risk of drugs 

Pulmonary diseases 

Felty syndrome 

Sjogren syndrome 

Lymphoma  

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Treatment paradigm 

Approach considerations: Rheumatoid arthritis patients require an integrated approach involving pharmacologic and nonpharmacologic therapies. Nonpharmacologic treatments include exercise, diet, massage, counseling, stress reduction, physical therapy, and surgery. Early initiation of DMARD therapy is recommended for slowing disease progression and potentially causing remissions. A treat-to-target approach aims for low disease activity or remission. 

Pharmacologic therapy: RA is a rheumatic disease with primary treatment goals to control disease activity, slow joint damage progression, and minimize pain. Medications include nonbiologic and biologic DMARDs, with biologic agents being more effective than nonbiologic treatments. Etanercept and rituximab are the most effective treatments. However, DMARDs’ immunosuppressive effects increase infection risk. ACR guidelines recommend vaccinations for RA patients. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of non-pharmacological approaches

Assistive devices, Education, Exercise, and Physical or occupational therapies: 

Rehabilitation for RA patients aim to relieve pain, improve range of motion, enhance strength and endurance, prevent deformities, and provide counselling and educational services, using nonpharmacologic therapeutic modalities. 

Heat and cold therapies:  

Heat is an effective method for relieving joint pain and stiffness in RA patients preparing joints for range of motion exercises, stretching, and muscle strengthening. Heat can be delivered through various methods while cold treatment is preferred for acutely inflamed joints. 

Orthotics and splints: 

Orthotic devices in RA rehabilitation helps to alleviate pain improve function, reduce deformity, and correct biomechanical misalignment. Lower-extremity orthoses for foot and ankle joints provide stability and alignment. 

Occupational therapy:  

it is beneficial for patients with RA aiming to efficiently use joints and tendons by reducing joint tension with splints and adapt daily life. Adaptive equipment:  

Assistive devices aid patients with RA in various activities by reducing joint stress, conserving energy, and relieving pain with training provided by physical and occupational therapists. 

Joint- protection education: educating patients about Joint-protection helps patients to prevent overuse and biomechanical stresses, utilizing adaptive equipment, good posture, avoiding inflammation, modifying tasks, and using appropriate splints. 

Use of DMARDs (Immunomodulators)

Leflunomide: This medication reduces the signs and symptoms of RA. It is an inhibitor of pyrimidine synthesis which is involved in blocking autoimmune and thereby inflammation. This drug also inhibits the enzyme dihydroorotate that is involved in pathway of pyrimidine synthesis and possess antiproliferatibve property.  

Sulfasalazine: It is used in patients who don’t have a proper response to salicylates or any other NSAIDS. It works locally to reduce response to inflammation and systemically inhibit the synthesis of prostaglandins. 

Hydroxychloroquine: It is approved in treating acute or chronic rheumatoid arthritis.  

Rituximab: It is generally used in combination with methotrexate. In adults who have severe rheumatoid arthritis but not responding adequately to treatment by one or more TNF blockers, it works well. Treatment using rituximab reduces CD20+ B cells. In combination with MTX, typically, there are two IV doses of 1000 mg each over 14 days interval. 

Use of DMARDs

Methotrexate: This is an antagonist of folic acid which is approved to manage severe and active RA in case of patients with inadequate response to full-dose NSAIDs. 

Tocilizumab: It is an inhibitor of IL-6 receptor and indicated in the treatment of moderate to severe RA in patients who had unsatisfactory response to one or more TNF-antagonist treatments. 

Azathioprine: Though it is not a first-line agent, this is sometimes used to reduce signs and symptoms in active RA especially in patients with diseases of connective tissue like SLE. 

Anakinra: this is a recombinant and nonglycosylated form of human IL-1 receptor antagonist which is used in reducing the signs and symptoms and lowering the progression of structural damage of moderate to severe RA. 

Abatacept: This is a selective modulator of costimulation which inhibits the activation of T-cells by binding to CD80 and CD-86, which further leads to blocking of their interaction with CD28. 

Use of DMARDs (TNF inhibitors)

Infliximab: This is a chimeric monoclonal antibody which acts against TNF-alpha and approved to inhibit the progressive structural damage, and improve physical function in those suffering from moderate to severe RA. 

Etanercept: It is a bivalent p75-TNF receptor attached to Fc portion of IgG and induces major clinical damage. 

Adalimumab: This is a recombinant human immunoglobulin1 monoclonal antibody which is specific for TNF in humans. It binds particularly to TNF-alpha and inhibits the interaction with cell-surface TNF receptors like p55 and p75. 

Use of DMARDs (JAK inhibitors)

Tofacitinib:  

It is a JAK inhibitor used as a second line of treatment for moderate to severe RA in individuals producing inadequate response to methotrexate.  

Use of tetracyclines

Minocycline:  

This drug has anti-inflammatory effects thus inhibits the migration of inflammatory cells and lymphocytes transformation. 

Use of NSAIDS

Ibuprofen: It is indicated in patients with mild to moderate pain. This inhibits the inflammatory reactions by reducing the synthesis of prostaglandins. 

Diclofenac: This is an anti-inflammatory agent believed to act by inhibiting COX, an essential factor in prostaglandins biosynthesis. 

Ketoprofen: This is used to relieve mild to moderate pain and inflammation. It acts by reversibly inhibiting COX-1 and COX-2 enzymes thereby reducing the synthesis of prostaglandins. 

Use of analgesics (other)

Acetaminophen: It is used to reduce pain in individuals who have known hypersensitivity to aspirin or NSAIDs. 

Use of opioid analgesics

Tramadol: Immediate release formulation of this drug is approved in the treatment of moderate to severe pain in adults. 

Use of topical skin products

Diclofenac topical: It is approved to use in patients with osteoarthritis and known to possess analgesic effects. 

Use of corticosteroids

Prednisone: This is an immunosuppressant used in treating autoimmune disorders and may reduce inflammation via reversal of increased capillary permeability and suppression of activity of polymorphonuclear leukocytes. 

Methylprednisolone: It lowers inflammation by reversal of increased capillary permeability and suppression of migration of polymorphonuclear leukocytes. 

Use of chelators

Pencillamine: This drug reduces the circulating IgM rheumatoid factor and activity of T-cell. This is generally indicated in patients with active, severe RA who are irresponsive to conventional therapy. 

Intervention with a procedure

Surgical intervention in RA patients can relieve pain, correct deformities, and improve function through techniques like myofascial techniques, excisions, reconstructions, joint fusions, and joint replacements. 

Use of phases of management in treating Rheumatoid arthritis

Rheumatoid arthritis (RA) is non-curable disorder requiring patient education from nurses, pharmacists, rheumatologists, and primary care providers. It is characterized by frequent relapses and worse outcomes in patients with high autoantibodies, specific genotypes, early onset, multiple joint involvement, and female gender. 

Medication

 

valdecoxib

10

mg

Tablet

Oral

once a day



rofecoxib

25 - 50

mg

Orally 

once a day



etoricoxib

90

mg

Tablet

Oral

once a day



etodolac

400 mg immediate release 2 times daily
Or
300 mg immediate release 2 to 3 times a day
Or
500 mg immediate release 2 times a day
Or
400 mg to 1 g extended release once a day



prednisone (Rx)

≤10 mg/day orally Immediate release
5 mg/day orally Delayed release
Maintenance: low dose taken at bedtime to decrease morning stiffness with rheumatoid arthritis (RA)



prednisone (Rx)

≤10 mg/day orally Immediate release
5 mg/day orally Delayed release
Maintenance: low dose taken at bedtime to decrease morning stiffness with rheumatoid arthritis (RA)



aspirin

3

g

oraly

in divided doses as needed



sulfasalazine

0.5-1 g/day delayed release orally divided 2x; increase weekly 2 g/day 2x; if response inadequate, may increase to 3 g/day



fenoprofen 

300 - 600

mg

Tablets

Orally 

every 8 hrs



indomethacin 

Immediate release:

25 - 50

mg

Tablet

Orally 

every 12 hrs

Do not exceed 200mg/day
Extended release-75-150mg/day orally in single dose or divided every 12 hours



nabumetone 

In case of renal impairment, 500 mg orally once daily:

1000

mg

Tablet

Orally 

once a day



certolizumab pegol 

400

mg

Solution

Subcutaneous (SC)

every 2 weeks



hydroxychloroquine sulfate 

400 - 600

mg

Tablet

Orally 

once a day



ketoprofen 

Immediate release:

75

mg

Tablet

Orally 

every 8 hrs

50mg orally every 6 hours
Extended release-200mg orally every day



golimumab 

50 mg subcutaneous (SC) every Month
Or
2 mg/kg IV at weeks 0 and week 4, then every 8Weeks



adalimumab-aacf 

40

mg

Solution

Subcutaneous (SC)

every two weeks



prednisolone 

5-7.5mg orally every day



penicillamine 

Initial dose:125-250mg/day orally
Maintenance dose: If there is no improvement and the patient tolerates it, the dose may be increased by an additional 125–250 mg every 1-3 months, up to 500–750 mg daily



gold sodium thiomalate (Discontinued) 

Indicated in patients with active rheumatoid arthritis who have failed trials of NSAIDs
1st week- 10 mg intramuscularly
2nd week- 25 mg intramuscularly
Later every week for 20 weeks, 25-50 mg intramuscularly, or until toxicity is achieved
Streamline the dose to 50 mg intramuscularly every 2-4 weeks
The drug is not recommended when CrCl is less than 50 ml/min



auranofin 

Indicated in patients with active rheumatoid arthritis who have failed trials of NSAIDs
6 mg orally each day divided twice daily Increase the dose to 9 mg/day divided thrice daily for 3 months br> After 3 months, if no response is seen, discontinue the drug



esomeprazole/naproxen  

Take one tablet orally two times a day, ensuring that at least 30 minutes before the meal



choline magnesium trisalicylate 

1000-3000 mg orally 2-3 times a day



cat’s claw 

Extract without tetracyclic oxindole alkaloids: take 60 mg orally three times daily



rose hips 

Tea
Infuse 2 to 2.5 grams of crushed rose hips in 150 ml boiling water for 10 to 15 minutes, then filter the liquid before consuming
Supplement
500 to 750 mg daily, preferably taken with food



boswellia 

Extract: take 3600 mg daily



diclofenac 

diclofenac potassium- 50 mg orally 2-3 times daily
diclofenac sodium- 50 mg orally thrice daily or 75 mg orally every 12 hours
Extended-release- 100 mg orally once daily, may increase the dose to 100 mg every 12 hours



diclofenac 

diclofenac potassium- 50 mg orally 2-3 times daily
diclofenac sodium- 50 mg orally thrice daily or 75 mg orally every 12 hours
Extended-release- 100 mg orally once daily, may increase the dose to 100 mg every 12 hours



diclofenac/misoprostol 

50mg/200mcg as 1 tablet orally thrice daily
Do not increase the dose of misoprostol to more than 200 mcg/dose or 800 mcg each day
75mg/200mcg as 1 tablet orally thrice daily
Do not increase the dose of misoprostol to more than 200 mcg/dose or 800 mcg each day
If the dose is not tolerated, reduce the frequency to twice daily



cyclosporine 

Neoral or Gengraf: Administer 1.25 mg/kg orally twice a day
can increase the dose by 0.5 to 0.75 mg/kg/day after 8 weeks, and if needed again after 12 weeks, Do not exceed 4 mg/kg in a day
If no improvement is shown after 16 weeks, discontinue.



sarilumab 

200 mg by subcutaneous every 2 weeks
Those with slightly to severely active rheumatoid arthritis (RA) who have not responded well or have become intolerable to at least one disease-modifying antirheumatic medication should take this medication (DMARDs) MTX (methotrexate) or other traditional DMARDs may be combined with it or used as a monotherapy
Dosage Modifications
Hold off treatment until the infection is under control if it is severe or opportunistic
ANS
>1000 cells/mm3: Continue administering dose
500 to 1000 cells/mm3: Hold therapy off until ANC >1000; then, resume at 150 mg
Every two week, and then as clinically necessary, raise to 200 mg every 2 week
500 cells/mm3 or less: Stop

Low Platelets
50,000–100,000 cells/mm3 Continue treatment at 150 mg every two weeks and then raise it to 200 mg every two weeks as necessary until platelets reach more than100,000
<50,000 cells/mm3: Stop if verified by additional tests
PMR
Platelet count <100,000/mm3 for Thrombocytopenia
Neutropenia should be stopped
No research has been done on dosage adjustments for patients with these illnesses and PMR
Renal impairment
Mild-to-moderate: No dose adjustment is necessary
Severe: No study performed
Hepatic impairment
No study performed
Dosing Considerations
Before to starting therapy, check your platelet count. Then, check your platelets 4 to 8 weeks later and then every 3 months after that
Before beginning, check for latent tuberculosis (TB); if positive, discuss treating for TB first before using sarilumab
Because there is a higher risk of immunosuppression and infection when biological DMARDs are administered together, this should be avoided
Coadministration with biological DMARDs has not been thoroughly researched



tolmetin 

Not more than 1800 mg each day
200 to 600 mg orally every eight hours
Administration
Take with 8-to-12-ounce water to ignore gastro-intestinal effects



azapropazone 

1.2 gm orally each day in 2 to 4 divided doses
Dose Adjustments
In the case of renal impairment;
when CrCl is 50-75 ml/min, reduce the dose by 1/3rd to 1/2nd
when CrCl is less than 50 ml/min, reduce the dose by 1/2nd to 2/3rd



talniflumate 

Take a dose of 250 mg orally three times a day



abatacept 

IV bolus

weight <60 kg: 500 mg
weight 60-100 kg: 750 mg
weight >100 kg: 1000 mg

Maintenance: Repeat the aforementioned dose every two weeks for two weeks, then every four weeks

Subcutaneous (SC)

You can start SC with or without an IV loading dose
Give the first SC injection if an IV loading dose is taken within a day following the infusion
125 mg SC every 7 days

Making the switch from IV to SC:

Instead of the planned IV dosage, administer the first SC dose



benorilate 

Administer 2g twice a day.
Do not exceed 6g in a day.
Analgesia
Administer 2g twice a day.

Osteoarthritis
Administer 2g twice a day.



lornoxicam 

Take a dose of 12 mg daily in 2 to 3 divided doses
Daily dose not more than 16 mg



tenoxicam 

Take a dose of 10 to 20 mg orally one time daily



phenylbutazone 


Indicated for Rheumatic disorders
Nearly 600 mg every day in divided doses. Following 1-3 days, diminish the dose to the lowest effective dose
It should not be used for more than one week
Acute gout
Nearly 600 mg every day might be needed
Following 1-3 days, diminish the dose to the lowest effective dose It should not be used for more than one week



pirprofen 


Indicated for Rheumatoid arthritis, Osteoarthritis
600 mg to 800 mg orally every day



tetracosactide 

1 mg/day, can administer dose every 12 hours in acute or critical cases Maintenance dose: 1 mg given every 2 to 3 days. For good responders, can reduce the dosage to 0.5 mg every two to three days or 1 mg weekly



tocilizumab 

Intended for use in adults who have moderate-to-severe active rheumatoid arthritis and have not responded adequately to one or more disease-modifying antirheumatic drugs (DMARDs)
It can be used either by itself or in conjunction with methotrexate or other DMARDs
However, it is not advisable for patients whose ANC (absolute neutrophil count) is less than 1,000/mm3, those with a platelet count lower than 50,000/mm3, or those with ALT/AST levels exceeding 10 times the upper limit of normal

When administered through intravenous (IV) infusion, the initial dose is 4 mg/kg IV every 4 weeks
This dosage may be increased to 8 mg/kg every 4 weeks based on the patient's clinical response
It's important not to exceed a dose of 800 mg every 4 weeks

For subcutaneous (SC) injection, the dosage varies based on the patient's weight
For those weighing less than 100 kg, the recommended dose is 162 mg SC every other week, with the possibility of increasing to weekly injections depending on clinical response
Patients weighing 100 kg or more should receive 162 mg SC injections on a weekly basis



etoricoxib 

Take a dose of 60 mg orally one time daily and it may be raised to 90 mg one time daily as required



tiaprofenic acid 

Treatment of rheumatoid arthritis with tiaprofenic acid usually starts with a dose of 600 mg per day in divided doses of 2 or 3, and the maximum dose should not exceed 600 mg per day



droxicam 

The suggested dose is 20 mg orally daily



benoxaprofen (discontinued) 

Take 600 mg a day orally
In some cases the dose may be elevated to 800 mg



aurothioglucose 

Test dose :

10

mg

Solutions

Intramuscular (IM)

one time only


After one week, administer 25mg, intramuscular and repeat a progressive dose of 0.8 to 1g is attained

Maintenance dose: 50mg intramuscular every 3 to 4 weeks, depending on response to the drug



baricitinib 

2

mg

Tablets

Orally 

once a day


It is not advised to use this medication in conjunction with biologic DMARDs, other Janus kinase (JAK) inhibitors, or potent immunosuppressants (such as cyclosporine or azathioprine)
This medication can be taken either alone or in conjunction with other nonbiologic DMARDs, such as methotrexate
Indication: For the management of individuals with moderate to serious active rheumatoid arthritis who did not respond well to at least one TNF inhibitor



betamethasone sodium phosphate and betamethasone acetate 

0.5-2.0 mL is given as intra-articular Injectable Suspension, to relieve pain, stiffness, and soreness



sodium aurothiomalate 

Administer dose of 10 mg intramuscularly in first week and 25 mg in next week, then 25 to 50 mg intramuscularly every week for 20 weeks



epirizole 

The drug has been investigated in a clinical trial; it's supposed to be discontinued, and its current status is unknown



flunoxaprofen 

In vivo, data suggests taking 100 mg orally two times daily
The treatment duration is sixty days



nifenazone 

In vivo, data suggests taking 750 to 2,000 mg a day through the oral route in divided doses



anakinra 

Administer dose of 100 mg subcutaneously daily



rofecoxib 

Take a dose of 25 to 50 mg orally one time in a day



tenidap 

40 - 120

mg

once a day



sulindac 

Take 150 mg to 200 mg two times a day orally The maximum dose is 400 mg Take the minimum efficient amount for the shortest duration possible



Dose Adjustments

Limited data is available

indomethacin 

Immediate release-25-50mg orally every 8-12 hours. Do not exceed 200mg/day

Extended release-75-150mg/day orally in a single dose or divided every 12 hours



meclofenamate 

Take a dose of 200 to 400 mg orally daily divided into 3 to 4 equal doses



niflumic acid 

A medicine used to treat rheumatoid arthritis that is both analgesic and anti-inflammatory
The usual dose recommended is 250 mg sos via oral administration 3 or 4 times daily with a limit of 1500 mg per day
Application of ointment or cream (3%) or gel (2.5%) onto the affected areas



Dose Adjustments

Limited data is available

ibuprofen 

800 mg, 600 mg, 400 mg, or 300 mg orally every 6-8 hours; should not exceed more than 3200 mg daily



Dose Adjustments

Dosage Modifications
Renal function is significantly impaired: Monitor closely and consider lowering the dosage if necessary
Avoid use in those with severe hepatic impairment

piroxicam 

20mg orally once a day.do not exceed 30-40mg per day



azathioprine 

Take an initial dose of 50 to 100 mg daily orally for minimum 12 weeks



 

indomethacin 

<2 years: safety and efficacy not established
2-14 years:1-2mg/kg/day orally every 6-12hours.Do not exceed 4mg/kg/day
>14 years:25-50 mg orally/per rectum every 8-12 hours



certolizumab pegol 

Safety and efficacy are not seen in pediatrics:



etoricoxib 

For ≥16 years old:
Take a dose of 60 mg orally one time daily and it may be raised to 90 mg one time daily as required



aurothioglucose 

For children of 6 to 12 years of age
Test dose:

0.25

mg/kg

Solutions

Intramuscular (IM)

one time only


After one week, administer 0.25mg/kg per dose, intramuscular
Maintenance dose: 0.75- 1mg/kg per dose with a maximum dose of 25mg intramuscular every 3 to 4 weeks (total number of doses should be 20)



rofecoxib 

For 2 to 17 years old:
Take a dose of 0.6 mg /kg to a maximum of 25 mg orally daily



sulindac 

Take 150 mg to 200 mg two times a day orally
The maximum dose is 400 mg
Take the minimum efficient amount for the shortest duration possible



 

choline magnesium trisalicylate 

500-1500 mg orally 2-3 times a day



azapropazone 

For more than 60 years, 300 mg twice daily
Dose Adjustments
In the case of renal impairment;
when CrCl is 50-75 ml/min, reduce the dose by 1/3rd to 1/2nd
when CrCl is less than 50 ml/min, reduce the dose by 1/2nd to 2/3rd



Media Gallary

Rheumatoid arthritis

Updated : July 4, 2024




Rheumatoid arthritis is an inflammatory condition of the joints caused by the immune system attacking its own tissues. It can affect any joint but is common in the wrist and fingers. The disease is highly symmetrical; that means if one hand has it, the other probably will too. Moreover, it progresses from small joints to large ones as time goes on. Swollen and painful joints result from a thickened synovium. 

Joints contain the end of a bone called cartilage. This cushion supports against shock when we move. Eventually, the cartilage is worn due to the disease’s inflammation which is the consequence of RA. Consequently, wear and tear of cartilage makes both pieces of the joint or parts of the joints rub against each other and destroy them. This makes to the weakened bones. 

Rheumatoid arthritis (RA) is more common in the United States and other Western countries of northern Europe where it occurs with about 40 cases per 100,000 people annually. According to epidemiologic information, the lifetime risk of developing this disease is 3.6% for women and 1.7% for men. Furthermore, it has been noted that those between 65 to 80 years have shown maximum susceptibility to rheumatism. 

Patients diagnosed with rheumatoid arthritis (RA) tend to produce antibodies against proteins with certain features. The post-translational modification of arginyl residues by peptidyl arginine deaminases leads to the production of citrulline, an amino acid. The antibodies are called anti-citrullinated protein antibodies (ACPAs) and can be of IgA, IgG or IgM type.  

When these proteins are bound by antibodies, they trigger complement system activation. Antibodies in RA which react to them are called seropositive RA. It is believed that repetitive provocation of innate immunity marks environment-induced RA. One example is smoking which activates alveolar macrophages to release peptidyl arginine deiminase hence converting arginine to citrulline in the respiratory tract. 

During this process a neoantigen is formed which produces an immune reaction, what eventually leads to antibodies development in the body which are specific against citrullinated proteins. Furthermore, RA symptoms are closely associated with production of antibodies reactive towards post-translationally-modified proteins known as anti-carbamylated protein (anti-CarP) antibodies. Homocitrulline is a result of lysine transformation by cyanide as it causes carbamylation to take place. 

Homocitrulline shares a common molecular structure with citrulline but anti-CarP antibodies are different and have been associated with RA in both ACPA-positive and ACPA-negative persons. In about 40% of RA patients, anti-acetylated protein antibodies were recently described mostly in seropositive patients. RA can be linked to microbiome dysbiosis due to the acetylation process which forms this disease. 

Rheumatoid arthritis (RA) is believed to be due to an interaction between the patient’s environment and genotype. The precise cause of rheumatoid arthritis remains unclear. The levels of an increasing risk for RA are related to the genetic susceptibility which is indicated by the heritability for seropositive and seronegative RA in the range of 40%-65%. RA risk is higher as alleles HLA-DRB1*10, HLA-DRB104 and HLA-DRB101 are more frequent. 

There is a common epitope shared by these HLA_DRB1 alleles within the third hypervariable region of their DRB1 chain made up of a sequence of five conserved amino acids that has been linked to a high chance of developing RA. Other genes, including IL-10 and STAT-4 that are believed to play a part in determining who gets RA also show variability. 

Discovery of single nucleotide polymorphisms (SNPs) in genes such as PTPN2, MIR146A, and PSORS1C1 is related with RA. Additionally, alteration of the gut microbiome structure and function has been identified with RA. Gut microbiota dysbiosis due to less diversity as compared to healthy individuals is one of the main characteristics of RA in patients with this condition. 

Rheumatoid arthritis is a constant illness with no established cure yet. Each patient has multiple episodes that end up being bad including higher disability levels and sometimes even death occurring. Early detection within the first 6 months of showing symptoms after the onset of the disease can lead to increased ability to work and decreased severity of illness as indicated by number of swollen or tender joints. 

Be that as it may, the rate of death is approximately equal for individuals who receive early treatment as well as those who receive late treatment, it is much better than that for people who do not get any treatment them at all six months after symptoms appear. 

RA refers to long-term spherical arthritis (synovitis), mostly in the feet and hands in an identical way. This is characterized by hand or foot symmetric polyarthritis in most of the cases though any joint which possess synovial membrane may get involved. Still, RA can present variably over time, however it usually ends up with progressive joint destruction resulting into deformity as well as reduction of the ability to carry out daily activities. Rheumatoid arthritis (RA) may also affect organs like skin, heart, lungs and eyes not only joints. 

Juvenile idiopathic arthritis, which is sometimes known as juvenile rheumatoid arthritis, is the most common kind of childhood arthritis. The immunogenic alleles, clinical course, and functional result of the JIA in the majority of patients are unlike adult-onset RA. 

Patients who have RA may have problems while performing their daily routines such as putting on clothes; they might not also be able to stand, walk around the house or take care of themselves particularly if they cannot use their hands freely; sometimes these patients may even lose strength and face some other joint related problems like arthritis as well as feel tired. 

RA is the way it typically sets about its course with the later occurrence of overt joint inflammation or swelling after earlier systemic features like fever, malaise, arthralgias, and weakness. A tiny fraction (about 10 percent) has an explosive beginning marked by synovitis and extra-articular signs. Although rare, spontaneous recovery can happen, particularly within the first six months. 

It is important to examine the following: 

Swelling 

Tenderness 

Deformity 

Stiffness 

Limitation of motion 

Rheumatoid nodules 

Pain during movement 

Extra-articular manifestations 

In RA, joint involvement is featured and distinct. Usually, there is symmetric distribution of relatively involved small joints of hands and feet. The commonly affected joints are the metatarsophalangeal (MTP), knee, wrist, shoulder, metacarpophalangeal (MCP), proximal interphalangeal (PIP), ankle, hip, cervical spine, elbow and temporomandibular joints in this order. 

Inflammation is seen in the affected joints, and they are also swollen, tender to touch, warm, and they have limited motion range (ROM). Muscle atrophy in the hands between bones can appear as one characteristic of early condition. It is possible for joints and tendons to become destroyed which can cause problems such as ulnar deviation’ boutonniere’ swan neck deformities (flexion contractures of MCP and DIP joints) hammer toes; sometimes even locking of joints through bony outgrowths (ankylosis). 

Other common manifestations include: 

Tenosynovitis 

Periarticular osteoporosis 

Carpel tunnel syndrome 

Generalized osteoporosis 

Most patients suffer muscle atrophy secondary to joint inflammation. 

Examination of upper extremities 

Fingers: Synovitis causes deformity in the PIP joint, causing lateral bands to become flexors. Hyperextension of the DIP joint occurs as tendons shorten. Swan-neck deformity describes hyperextension at the PIP joint with DIP joint flexion. 

Metacarpophalangeal joints: Volar subluxation and ulnar deviation are common deformities that affect palmar skeletal arches and finger stability at metacarpophalangeal (MCP) joints. Ulnar deviation occurs when synovitis weakens the volar plate and collateral ligaments, allowing the flexor tendon to dislocate volarward and ulnarward. The supporting structures of extensor tendons may also become attenuated or destroyed. If the extensor tendon subluxation moves beyond the MCP joint, it acts as a flexor, further limiting finger extension. 

Wrists: Wrist deformities can include disruption of the radioulnar joint, ulnarly translocated lunate, zigzag deformity and rotational deformities.
Rotational deformities shorten carpal height and cause loss of cartilage. Dorsal subluxation of the ulna may lead to rupture of the extensor tendons, particularly in the presence of tenosynovitis. Impingement neuropathy may occur due to synovitis around flexor tendons resulting in decreased sensation, weakness and thenar muscle atrophy. Entrapment of the ulnar nerve at the wrist can cause reduced sensation and interosseous muscle weakness, especially if tenosynovitis is present.  

Elbow: This can often lead to elbow synovitis, contraction, olecranon bursitis, and rheumatoid nodules in the bursa and ulna with flexion deformities being common. 

Shoulders: It often impacts the shoulders causing tenderness, nocturnal pain and limited mobility. Symptoms include rotator cuff degeneration, glenoid damage, frozen shoulder syndrome and rare aromioclavicular arthritis which is less disabling than the other RA manifestations. 

Examination of lower extremities 

Feet and ankles: It is unusual for the ankle joint to become inflamed without affecting the midfoot or metatarsophalangeal (MTP) joints. Weight-bearing and chronic synovitis may lead to structural changes that eventually result in subluxation of the subtalar joint and loss of the foot arch contour. Over time, the MTP joints may develop deformities such as hallux valgus, hammer toes, and calluses. Pain may occur during weight-bearing activities when the second and third metatarsal heads become the major weight-bearing surfaces. 

Knees: It causes knee effusions and synovial thickening, leading to muscle atrophy and instability. Progressive cartilage loss and ligament weakening can cause deformities like genu valgus or varus, increasing energy expenditure during standing or walking. 

Hips: Involvement of hip is common in rheumatoid arthritis (RA), but symptoms may not be immediately apparent due to their deep location. Signs include limited motion or pain during movement and weight-bearing. Abnormalities can be detected using the Patrick maneuver and the Thomas test, which may indicate contracture. 

Cervical spine: Involvement of cervical spine in rheumatoid arthritis (RA) can lead to serious neurologic consequences, including neck pain and occipital headaches. Most patients have had RA for over 10 years and experience stiffness throughout their neck’s range of motion. Neurological involvement can range from radicular pain to spinal cord lesions, resulting in weakness, sphincter dysfunction, sensory deficits, and abnormal reflexes. Cervical myelopathy typically develops gradually and may not correlate with neck pain. Patients requiring intubation or neck manipulation should undergo a thorough cervical spine evaluation. 

Pain during movement, tenderness and stiffness: Rheumatoid arthritis (RA) is assessed through physical examination, focusing on joint motion limitations. Stiffness is usually caused by articular surface damage or soft tissue contractures. Heat can alleviate stiffness, but active exercise is most effective. Joint tenderness is elicited through direct palpation, with pain-sensitive structures like the enlarged synovial membrane, periarticular ligaments, and supporting structures. Pain during joint motion is often used to indicate tenderness in joints with difficulty in palpation due to overlying muscles and tissues.  

Deformity, limitation of motion, and swelling: RA is a condition in which the synovial membrane becomes inflamed, causing swelling in small joints like those found in the hands and feet. This swelling can be due to joint effusions that may result in a Baker cyst being formed, which can cause severe pain if it ruptures. As time goes on, joint deformities develop as a result of damage done to supporting structures and articular by the inflammatory process. The hands and feet’s small joints are mostly affected by this process with more than 10% of all patients suffering from RA having deformities within their hand joints within two years of being diagnosed with the disease. If supporting structures become disrupted then there can be instability at these joints too; however, such movement may also be restricted significantly through mechanical factors because subluxations as well as deformities throughout different parts of one joint greatly reduce its range of motion. 

Extra-articular manifestations: RA is a systemic disease-causing generalized malaise and fatigue, with some more common in men, but similar prevalence across genders. 

Rheumatoid nodules: They occur in 25% of RA patients  but very rarely in the first year. They emerge on extensor surfaces or virtually on any part of the body that is affected by intense mechanical irritation. Elbow joint, heel, proximal ulna, occiput, ischial tuberosities, and subcutaneous tissues are commonly affected sites. 

RA also affects various organ systems like: 

  • Cardiac 
  • Renal 
  • Cutaneous 
  • Vascular 
  • Neurologic 
  • Ocular 
  • Gastrointestinal (GI) 
  • Hematologic 
  • Ocular 
  • Differential diagnoses 
  • Lyme disease 
  • Osteoarthritis 
  • Relapsing polychondritis 
  • Psoriatric arthritis 
  • Sjogren syndrome 
  • Paraneoplastic syndrome 
  • Fibromyalgia 
  • Lyme disease 
  • SLE 
  • Relapsing polychondritis 

Pain and joint disability in day to day life 

Anemia 

Gastrointestinal issues 

Osteoporosis 

Increased risk of drugs 

Pulmonary diseases 

Felty syndrome 

Sjogren syndrome 

Lymphoma  

Treatment paradigm 

Approach considerations: Rheumatoid arthritis patients require an integrated approach involving pharmacologic and nonpharmacologic therapies. Nonpharmacologic treatments include exercise, diet, massage, counseling, stress reduction, physical therapy, and surgery. Early initiation of DMARD therapy is recommended for slowing disease progression and potentially causing remissions. A treat-to-target approach aims for low disease activity or remission. 

Pharmacologic therapy: RA is a rheumatic disease with primary treatment goals to control disease activity, slow joint damage progression, and minimize pain. Medications include nonbiologic and biologic DMARDs, with biologic agents being more effective than nonbiologic treatments. Etanercept and rituximab are the most effective treatments. However, DMARDs’ immunosuppressive effects increase infection risk. ACR guidelines recommend vaccinations for RA patients. 

Assistive devices, Education, Exercise, and Physical or occupational therapies: 

Rehabilitation for RA patients aim to relieve pain, improve range of motion, enhance strength and endurance, prevent deformities, and provide counselling and educational services, using nonpharmacologic therapeutic modalities. 

Heat and cold therapies:  

Heat is an effective method for relieving joint pain and stiffness in RA patients preparing joints for range of motion exercises, stretching, and muscle strengthening. Heat can be delivered through various methods while cold treatment is preferred for acutely inflamed joints. 

Orthotics and splints: 

Orthotic devices in RA rehabilitation helps to alleviate pain improve function, reduce deformity, and correct biomechanical misalignment. Lower-extremity orthoses for foot and ankle joints provide stability and alignment. 

Occupational therapy:  

it is beneficial for patients with RA aiming to efficiently use joints and tendons by reducing joint tension with splints and adapt daily life. Adaptive equipment:  

Assistive devices aid patients with RA in various activities by reducing joint stress, conserving energy, and relieving pain with training provided by physical and occupational therapists. 

Joint- protection education: educating patients about Joint-protection helps patients to prevent overuse and biomechanical stresses, utilizing adaptive equipment, good posture, avoiding inflammation, modifying tasks, and using appropriate splints. 

Leflunomide: This medication reduces the signs and symptoms of RA. It is an inhibitor of pyrimidine synthesis which is involved in blocking autoimmune and thereby inflammation. This drug also inhibits the enzyme dihydroorotate that is involved in pathway of pyrimidine synthesis and possess antiproliferatibve property.  

Sulfasalazine: It is used in patients who don’t have a proper response to salicylates or any other NSAIDS. It works locally to reduce response to inflammation and systemically inhibit the synthesis of prostaglandins. 

Hydroxychloroquine: It is approved in treating acute or chronic rheumatoid arthritis.  

Rituximab: It is generally used in combination with methotrexate. In adults who have severe rheumatoid arthritis but not responding adequately to treatment by one or more TNF blockers, it works well. Treatment using rituximab reduces CD20+ B cells. In combination with MTX, typically, there are two IV doses of 1000 mg each over 14 days interval. 

Methotrexate: This is an antagonist of folic acid which is approved to manage severe and active RA in case of patients with inadequate response to full-dose NSAIDs. 

Tocilizumab: It is an inhibitor of IL-6 receptor and indicated in the treatment of moderate to severe RA in patients who had unsatisfactory response to one or more TNF-antagonist treatments. 

Azathioprine: Though it is not a first-line agent, this is sometimes used to reduce signs and symptoms in active RA especially in patients with diseases of connective tissue like SLE. 

Anakinra: this is a recombinant and nonglycosylated form of human IL-1 receptor antagonist which is used in reducing the signs and symptoms and lowering the progression of structural damage of moderate to severe RA. 

Abatacept: This is a selective modulator of costimulation which inhibits the activation of T-cells by binding to CD80 and CD-86, which further leads to blocking of their interaction with CD28. 

Infliximab: This is a chimeric monoclonal antibody which acts against TNF-alpha and approved to inhibit the progressive structural damage, and improve physical function in those suffering from moderate to severe RA. 

Etanercept: It is a bivalent p75-TNF receptor attached to Fc portion of IgG and induces major clinical damage. 

Adalimumab: This is a recombinant human immunoglobulin1 monoclonal antibody which is specific for TNF in humans. It binds particularly to TNF-alpha and inhibits the interaction with cell-surface TNF receptors like p55 and p75. 

Tofacitinib:  

It is a JAK inhibitor used as a second line of treatment for moderate to severe RA in individuals producing inadequate response to methotrexate.  

Minocycline:  

This drug has anti-inflammatory effects thus inhibits the migration of inflammatory cells and lymphocytes transformation. 

Ibuprofen: It is indicated in patients with mild to moderate pain. This inhibits the inflammatory reactions by reducing the synthesis of prostaglandins. 

Diclofenac: This is an anti-inflammatory agent believed to act by inhibiting COX, an essential factor in prostaglandins biosynthesis. 

Ketoprofen: This is used to relieve mild to moderate pain and inflammation. It acts by reversibly inhibiting COX-1 and COX-2 enzymes thereby reducing the synthesis of prostaglandins. 

Acetaminophen: It is used to reduce pain in individuals who have known hypersensitivity to aspirin or NSAIDs. 

Tramadol: Immediate release formulation of this drug is approved in the treatment of moderate to severe pain in adults. 

Diclofenac topical: It is approved to use in patients with osteoarthritis and known to possess analgesic effects. 

Prednisone: This is an immunosuppressant used in treating autoimmune disorders and may reduce inflammation via reversal of increased capillary permeability and suppression of activity of polymorphonuclear leukocytes. 

Methylprednisolone: It lowers inflammation by reversal of increased capillary permeability and suppression of migration of polymorphonuclear leukocytes. 

Pencillamine: This drug reduces the circulating IgM rheumatoid factor and activity of T-cell. This is generally indicated in patients with active, severe RA who are irresponsive to conventional therapy. 

Surgical intervention in RA patients can relieve pain, correct deformities, and improve function through techniques like myofascial techniques, excisions, reconstructions, joint fusions, and joint replacements. 

Rheumatoid arthritis (RA) is non-curable disorder requiring patient education from nurses, pharmacists, rheumatologists, and primary care providers. It is characterized by frequent relapses and worse outcomes in patients with high autoantibodies, specific genotypes, early onset, multiple joint involvement, and female gender. 

valdecoxib

10

mg

Tablet

Oral

once a day



rofecoxib

25 - 50

mg

Orally 

once a day



etoricoxib

90

mg

Tablet

Oral

once a day



etodolac

400 mg immediate release 2 times daily
Or
300 mg immediate release 2 to 3 times a day
Or
500 mg immediate release 2 times a day
Or
400 mg to 1 g extended release once a day



prednisone (Rx)

≤10 mg/day orally Immediate release
5 mg/day orally Delayed release
Maintenance: low dose taken at bedtime to decrease morning stiffness with rheumatoid arthritis (RA)



prednisone (Rx)

≤10 mg/day orally Immediate release
5 mg/day orally Delayed release
Maintenance: low dose taken at bedtime to decrease morning stiffness with rheumatoid arthritis (RA)



aspirin

3

g

oraly

in divided doses as needed



sulfasalazine

0.5-1 g/day delayed release orally divided 2x; increase weekly 2 g/day 2x; if response inadequate, may increase to 3 g/day



fenoprofen 

300 - 600

mg

Tablets

Orally 

every 8 hrs



indomethacin 

Immediate release:

25 - 50

mg

Tablet

Orally 

every 12 hrs

Do not exceed 200mg/day
Extended release-75-150mg/day orally in single dose or divided every 12 hours



nabumetone 

In case of renal impairment, 500 mg orally once daily:

1000

mg

Tablet

Orally 

once a day



certolizumab pegol 

400

mg

Solution

Subcutaneous (SC)

every 2 weeks



hydroxychloroquine sulfate 

400 - 600

mg

Tablet

Orally 

once a day



ketoprofen 

Immediate release:

75

mg

Tablet

Orally 

every 8 hrs

50mg orally every 6 hours
Extended release-200mg orally every day



golimumab 

50 mg subcutaneous (SC) every Month
Or
2 mg/kg IV at weeks 0 and week 4, then every 8Weeks



adalimumab-aacf 

40

mg

Solution

Subcutaneous (SC)

every two weeks



prednisolone 

5-7.5mg orally every day



penicillamine 

Initial dose:125-250mg/day orally
Maintenance dose: If there is no improvement and the patient tolerates it, the dose may be increased by an additional 125–250 mg every 1-3 months, up to 500–750 mg daily



gold sodium thiomalate (Discontinued) 

Indicated in patients with active rheumatoid arthritis who have failed trials of NSAIDs
1st week- 10 mg intramuscularly
2nd week- 25 mg intramuscularly
Later every week for 20 weeks, 25-50 mg intramuscularly, or until toxicity is achieved
Streamline the dose to 50 mg intramuscularly every 2-4 weeks
The drug is not recommended when CrCl is less than 50 ml/min



auranofin 

Indicated in patients with active rheumatoid arthritis who have failed trials of NSAIDs
6 mg orally each day divided twice daily Increase the dose to 9 mg/day divided thrice daily for 3 months br> After 3 months, if no response is seen, discontinue the drug



esomeprazole/naproxen  

Take one tablet orally two times a day, ensuring that at least 30 minutes before the meal



choline magnesium trisalicylate 

1000-3000 mg orally 2-3 times a day



cat’s claw 

Extract without tetracyclic oxindole alkaloids: take 60 mg orally three times daily



rose hips 

Tea
Infuse 2 to 2.5 grams of crushed rose hips in 150 ml boiling water for 10 to 15 minutes, then filter the liquid before consuming
Supplement
500 to 750 mg daily, preferably taken with food



boswellia 

Extract: take 3600 mg daily



diclofenac 

diclofenac potassium- 50 mg orally 2-3 times daily
diclofenac sodium- 50 mg orally thrice daily or 75 mg orally every 12 hours
Extended-release- 100 mg orally once daily, may increase the dose to 100 mg every 12 hours



diclofenac 

diclofenac potassium- 50 mg orally 2-3 times daily
diclofenac sodium- 50 mg orally thrice daily or 75 mg orally every 12 hours
Extended-release- 100 mg orally once daily, may increase the dose to 100 mg every 12 hours



diclofenac/misoprostol 

50mg/200mcg as 1 tablet orally thrice daily
Do not increase the dose of misoprostol to more than 200 mcg/dose or 800 mcg each day
75mg/200mcg as 1 tablet orally thrice daily
Do not increase the dose of misoprostol to more than 200 mcg/dose or 800 mcg each day
If the dose is not tolerated, reduce the frequency to twice daily



cyclosporine 

Neoral or Gengraf: Administer 1.25 mg/kg orally twice a day
can increase the dose by 0.5 to 0.75 mg/kg/day after 8 weeks, and if needed again after 12 weeks, Do not exceed 4 mg/kg in a day
If no improvement is shown after 16 weeks, discontinue.



sarilumab 

200 mg by subcutaneous every 2 weeks
Those with slightly to severely active rheumatoid arthritis (RA) who have not responded well or have become intolerable to at least one disease-modifying antirheumatic medication should take this medication (DMARDs) MTX (methotrexate) or other traditional DMARDs may be combined with it or used as a monotherapy
Dosage Modifications
Hold off treatment until the infection is under control if it is severe or opportunistic
ANS
>1000 cells/mm3: Continue administering dose
500 to 1000 cells/mm3: Hold therapy off until ANC >1000; then, resume at 150 mg
Every two week, and then as clinically necessary, raise to 200 mg every 2 week
500 cells/mm3 or less: Stop

Low Platelets
50,000–100,000 cells/mm3 Continue treatment at 150 mg every two weeks and then raise it to 200 mg every two weeks as necessary until platelets reach more than100,000
<50,000 cells/mm3: Stop if verified by additional tests
PMR
Platelet count <100,000/mm3 for Thrombocytopenia
Neutropenia should be stopped
No research has been done on dosage adjustments for patients with these illnesses and PMR
Renal impairment
Mild-to-moderate: No dose adjustment is necessary
Severe: No study performed
Hepatic impairment
No study performed
Dosing Considerations
Before to starting therapy, check your platelet count. Then, check your platelets 4 to 8 weeks later and then every 3 months after that
Before beginning, check for latent tuberculosis (TB); if positive, discuss treating for TB first before using sarilumab
Because there is a higher risk of immunosuppression and infection when biological DMARDs are administered together, this should be avoided
Coadministration with biological DMARDs has not been thoroughly researched



tolmetin 

Not more than 1800 mg each day
200 to 600 mg orally every eight hours
Administration
Take with 8-to-12-ounce water to ignore gastro-intestinal effects



azapropazone 

1.2 gm orally each day in 2 to 4 divided doses
Dose Adjustments
In the case of renal impairment;
when CrCl is 50-75 ml/min, reduce the dose by 1/3rd to 1/2nd
when CrCl is less than 50 ml/min, reduce the dose by 1/2nd to 2/3rd



talniflumate 

Take a dose of 250 mg orally three times a day



abatacept 

IV bolus

weight <60 kg: 500 mg
weight 60-100 kg: 750 mg
weight >100 kg: 1000 mg

Maintenance: Repeat the aforementioned dose every two weeks for two weeks, then every four weeks

Subcutaneous (SC)

You can start SC with or without an IV loading dose
Give the first SC injection if an IV loading dose is taken within a day following the infusion
125 mg SC every 7 days

Making the switch from IV to SC:

Instead of the planned IV dosage, administer the first SC dose



benorilate 

Administer 2g twice a day.
Do not exceed 6g in a day.
Analgesia
Administer 2g twice a day.

Osteoarthritis
Administer 2g twice a day.



lornoxicam 

Take a dose of 12 mg daily in 2 to 3 divided doses
Daily dose not more than 16 mg



tenoxicam 

Take a dose of 10 to 20 mg orally one time daily



phenylbutazone 


Indicated for Rheumatic disorders
Nearly 600 mg every day in divided doses. Following 1-3 days, diminish the dose to the lowest effective dose
It should not be used for more than one week
Acute gout
Nearly 600 mg every day might be needed
Following 1-3 days, diminish the dose to the lowest effective dose It should not be used for more than one week



pirprofen 


Indicated for Rheumatoid arthritis, Osteoarthritis
600 mg to 800 mg orally every day



tetracosactide 

1 mg/day, can administer dose every 12 hours in acute or critical cases Maintenance dose: 1 mg given every 2 to 3 days. For good responders, can reduce the dosage to 0.5 mg every two to three days or 1 mg weekly



tocilizumab 

Intended for use in adults who have moderate-to-severe active rheumatoid arthritis and have not responded adequately to one or more disease-modifying antirheumatic drugs (DMARDs)
It can be used either by itself or in conjunction with methotrexate or other DMARDs
However, it is not advisable for patients whose ANC (absolute neutrophil count) is less than 1,000/mm3, those with a platelet count lower than 50,000/mm3, or those with ALT/AST levels exceeding 10 times the upper limit of normal

When administered through intravenous (IV) infusion, the initial dose is 4 mg/kg IV every 4 weeks
This dosage may be increased to 8 mg/kg every 4 weeks based on the patient's clinical response
It's important not to exceed a dose of 800 mg every 4 weeks

For subcutaneous (SC) injection, the dosage varies based on the patient's weight
For those weighing less than 100 kg, the recommended dose is 162 mg SC every other week, with the possibility of increasing to weekly injections depending on clinical response
Patients weighing 100 kg or more should receive 162 mg SC injections on a weekly basis



etoricoxib 

Take a dose of 60 mg orally one time daily and it may be raised to 90 mg one time daily as required



tiaprofenic acid 

Treatment of rheumatoid arthritis with tiaprofenic acid usually starts with a dose of 600 mg per day in divided doses of 2 or 3, and the maximum dose should not exceed 600 mg per day



droxicam 

The suggested dose is 20 mg orally daily



benoxaprofen (discontinued) 

Take 600 mg a day orally
In some cases the dose may be elevated to 800 mg



aurothioglucose 

Test dose :

10

mg

Solutions

Intramuscular (IM)

one time only


After one week, administer 25mg, intramuscular and repeat a progressive dose of 0.8 to 1g is attained

Maintenance dose: 50mg intramuscular every 3 to 4 weeks, depending on response to the drug



baricitinib 

2

mg

Tablets

Orally 

once a day


It is not advised to use this medication in conjunction with biologic DMARDs, other Janus kinase (JAK) inhibitors, or potent immunosuppressants (such as cyclosporine or azathioprine)
This medication can be taken either alone or in conjunction with other nonbiologic DMARDs, such as methotrexate
Indication: For the management of individuals with moderate to serious active rheumatoid arthritis who did not respond well to at least one TNF inhibitor



betamethasone sodium phosphate and betamethasone acetate 

0.5-2.0 mL is given as intra-articular Injectable Suspension, to relieve pain, stiffness, and soreness



sodium aurothiomalate 

Administer dose of 10 mg intramuscularly in first week and 25 mg in next week, then 25 to 50 mg intramuscularly every week for 20 weeks



epirizole 

The drug has been investigated in a clinical trial; it's supposed to be discontinued, and its current status is unknown



flunoxaprofen 

In vivo, data suggests taking 100 mg orally two times daily
The treatment duration is sixty days



nifenazone 

In vivo, data suggests taking 750 to 2,000 mg a day through the oral route in divided doses



anakinra 

Administer dose of 100 mg subcutaneously daily



rofecoxib 

Take a dose of 25 to 50 mg orally one time in a day



tenidap 

40 - 120

mg

once a day



sulindac 

Take 150 mg to 200 mg two times a day orally The maximum dose is 400 mg Take the minimum efficient amount for the shortest duration possible



Dose Adjustments

Limited data is available

indomethacin 

Immediate release-25-50mg orally every 8-12 hours. Do not exceed 200mg/day

Extended release-75-150mg/day orally in a single dose or divided every 12 hours



meclofenamate 

Take a dose of 200 to 400 mg orally daily divided into 3 to 4 equal doses



niflumic acid 

A medicine used to treat rheumatoid arthritis that is both analgesic and anti-inflammatory
The usual dose recommended is 250 mg sos via oral administration 3 or 4 times daily with a limit of 1500 mg per day
Application of ointment or cream (3%) or gel (2.5%) onto the affected areas



Dose Adjustments

Limited data is available

ibuprofen 

800 mg, 600 mg, 400 mg, or 300 mg orally every 6-8 hours; should not exceed more than 3200 mg daily



Dose Adjustments

Dosage Modifications
Renal function is significantly impaired: Monitor closely and consider lowering the dosage if necessary
Avoid use in those with severe hepatic impairment

piroxicam 

20mg orally once a day.do not exceed 30-40mg per day



azathioprine 

Take an initial dose of 50 to 100 mg daily orally for minimum 12 weeks



indomethacin 

<2 years: safety and efficacy not established
2-14 years:1-2mg/kg/day orally every 6-12hours.Do not exceed 4mg/kg/day
>14 years:25-50 mg orally/per rectum every 8-12 hours



certolizumab pegol 

Safety and efficacy are not seen in pediatrics:



etoricoxib 

For ≥16 years old:
Take a dose of 60 mg orally one time daily and it may be raised to 90 mg one time daily as required



aurothioglucose 

For children of 6 to 12 years of age
Test dose:

0.25

mg/kg

Solutions

Intramuscular (IM)

one time only


After one week, administer 0.25mg/kg per dose, intramuscular
Maintenance dose: 0.75- 1mg/kg per dose with a maximum dose of 25mg intramuscular every 3 to 4 weeks (total number of doses should be 20)



rofecoxib 

For 2 to 17 years old:
Take a dose of 0.6 mg /kg to a maximum of 25 mg orally daily



sulindac 

Take 150 mg to 200 mg two times a day orally
The maximum dose is 400 mg
Take the minimum efficient amount for the shortest duration possible



choline magnesium trisalicylate 

500-1500 mg orally 2-3 times a day



azapropazone 

For more than 60 years, 300 mg twice daily
Dose Adjustments
In the case of renal impairment;
when CrCl is 50-75 ml/min, reduce the dose by 1/3rd to 1/2nd
when CrCl is less than 50 ml/min, reduce the dose by 1/2nd to 2/3rd



Free CME credits

Both our subscription plans include Free CME/CPD AMA PRA Category 1 credits.

Digital Certificate PDF

On course completion, you will receive a full-sized presentation quality digital certificate.

medtigo Simulation

A dynamic medical simulation platform designed to train healthcare professionals and students to effectively run code situations through an immersive hands-on experience in a live, interactive 3D environment.

medtigo Points

medtigo points is our unique point redemption system created to award users for interacting on our site. These points can be redeemed for special discounts on the medtigo marketplace as well as towards the membership cost itself.
 
  • Registration with medtigo = 10 points
  • 1 visit to medtigo’s website = 1 point
  • Interacting with medtigo posts (through comments/clinical cases etc.) = 5 points
  • Attempting a game = 1 point
  • Community Forum post/reply = 5 points

    *Redemption of points can occur only through the medtigo marketplace, courses, or simulation system. Money will not be credited to your bank account. 10 points = $1.

All Your Certificates in One Place

When you have your licenses, certificates and CMEs in one place, it's easier to track your career growth. You can easily share these with hospitals as well, using your medtigo app.

Our Certificate Courses

Up arrow