Systemic lupus erythematosus (SLE) is an autoimmune disease in which the body’s immune system mistakenly attacks its own tissues, resulting in inflammation and damage to various organs. Therapy is directed more toward controlling the disease progression rather than achieving complete eradication. The usual treatment is anti-inflammatory drugs, immune suppressants, steroids, and antimalarial medicines. Studies show that chronic organ damage usually occurs in SLE patients who do not have well-controlled disease, especially during flare-up periods and with long-term steroid therapy. Early detection of SLE and treatment with emerging biologicals and immunosuppression while minimizing steroids may serve to avoid permanent damage.
Anifrolumab is a monoclonal antibody that inhibits type I interferons (T1IFNs) by blocking their receptor and preventing their downstream effects. It was tested in the two TULIP Phase 3 studies, which were double-blind, randomized trials that lasted 52 weeks.
In the TULIP-2 trial, it was observed that anifrolumab was more beneficial than a placebo for patients from moderate to severe SLE who were already following their standard care after a long term of treatment. The efficacy of the chosen treatment regime was achieved through BICLA response treatment and was based on the British Isles Lupus Assessment Group (BILAG). These positive results were also produced in the TULIP-1 trial. Moreover, the 3-year extension study not only confirmed the anifrolumab’s long-term safety and tolerability but also its effectiveness. Anifrolumab has been approved for use in over 50 countries including Japan, Australia, Canada, the United States, and European nations.
While anifrolumab has shown the ability to improve disease activity and reduce the use of glucocorticoids, more studies are needed to understand its long-term effectiveness in preventing organ damage compared to conventional therapies. In the long-term extension (LTE) trial, patients who were initially given a placebo in the TULIP-1 or -2 trials were randomly assigned to switch to anifrolumab plus standard care at a 4:1 ratio. The placebo group exhibited a high dropout rate. Of the 368 patients who were initially on the placebo, 270 (73.4%) completed the first year of the study, but only 54 (14.7%) continued the study while still receiving placebo. On the other hand, of the 361 patients who received 300 mg of anifrolumab in the original trials, 296 (82.0%) completed the first year, and 178 (49.3%) stayed in the LTE study on anifrolumab.
The initial 300 mg dose of anifrolumab administration placed patients into the experimental anifrolumab treatment group of the TULIP trials. Standard therapy groups were identified through an enrollment process with eligible patients who received this treatment. Propensity score and censoring weighting adjusted for initial imbalances as well as the impact of dropouts. The research evaluated changes in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score throughout week 208, starting from the baseline time point. Research investigators measured the duration before the first systemic increase in SDI score values as a secondary objective.
This study used data from the TULIP trials (-1, -2, and LTE) as well as from the University of Toronto Lupus Clinic (UTLC). The TULIP trials took place between 2015 and 2021. TULIP-1 compared the safety and efficacy of two doses of anifrolumab (150 mg and 300 mg) against a placebo, while TULIP-2 focused on the 300 mg dose of anifrolumab compared to a placebo. Both trials lasted for 52 weeks.
Since 1970, the UTLC, located in Toronto, has established a long-term research program for SLE patients. The standardized protocol requires patients to visit every 3 to 4 months where they receive treatment along with demographic, clinical, laboratory, and treatment data collection.
In the study, 354 patients received anifrolumab, and 561 patients received real-world standard of care (RW SOC). After adjusting for differences, the average change in the SDI score was 0.416 points lower in the anifrolumab group compared to the RW SOC group, which means patients in the anifrolumab group experienced less organ damage (95% Confidence interval (CI): −0.582, −0.249; P < 0.001). Additionally, patients on anifrolumab were 59.9% less likely to experience progression of organ damage over 208 weeks (hazard ratio: 0.401; 95% CI: 0.213, 0.753, P = 0.005).
Patients treated with anifrolumab developed lower organ damage rates compared to those receiving standard treatment patients after 208 weeks. The combination of standard therapy with anifrolumab delays organ damage development and onset in patients suffering from moderate to severe SLE.
References: Touma Z, Bruce IN, Furie R, et al. Reduced organ damage accumulation in adult patients with SLE on anifrolumab plus standard of care compared to real-world external controls. Annals of the Rheumatic Diseases. Published February 7, 2025. Reduced organ damage accumulation in adult patients with SLE on anifrolumab plus standard of care compared to real-world external controls – Annals of the Rheumatic Diseases
