Rheumatology-Rhumatologie

 In this article, we review the mechanism of anti-IL-6 in the treatment of RA, provide the key efficacy
and safety data from clinical trials of approved anti-IL-6, TCZ, as well as six candidate IL-6 blockers
including sarilumab, ALX- 0061, sirukumab, MEDI5117, clazakizumab, and olo ...Cited by 1 Cite Save

Via Krishan Maggon

The safety and efficacy profiles in clinical trials of olokizumab, sarilumab and sirukumab are similar and are consistent with those observed in RA patients treated with tocilizumab. Furthermore, the clinical efficacy of these IL-6 inhibitors is similar to that of TNF inhibitors in patients with MTX-IR and TNF-IR. Screening of biomarkers or genetics in each RA patient, for instance, baseline serum levels of TNF and/or soluble IL-6R, may help to predict the efficacy of each drug and to select patients for cytokine-oriented targeted therapies.33 However, better strategies are warranted for selecting and identifying appropriate patients earlier once bDMARDs targeting IL-6 are launched in the near future. We also need to determine whether there are important differences between the many IL-6 inhibitors and which are suitable for particular patients, otherwise companies may waste time and money in development.

Via Krishan Maggon

Abstract

Objectives The safety and efficacy of sirukumab, an anti-interleukin-6 (IL-6) monoclonal antibody, were evaluated in a 2-part, placebo-controlled phase II study of patients with active rheumatoid arthritis (RA) despite methotrexate therapy.

Methods In Part A (proof-of-concept), 36 patients were randomised to placebo or sirukumab 100 mg every 2 weeks (q2w) through week 10, with crossover treatment during weeks 12–22. In Part B (dose finding), 151 patients were randomised to sirukumab (100 mg q2w, 100 mg q4w, 50 mg q4w, or 25 mg q4w) through week 24, or placebo through week 10 with crossover to sirukumab 100 mg q2w (weeks 12–24). The proportion of patients with an American College of Rheumatology 50 (ACR50) response and the change from baseline in the 28-joint count disease activity score using C-reactive protein (DAS28-CRP) were determined. Safety was evaluated through week 38 in both parts.

Results The primary endpoint (ACR50 at week 12 in Part B) was achieved only with sirukumab 100 mg q2w versus placebo (26.7% vs 3.3%; p=0.026). Greater improvements in mean DAS28-CRP at week 12 were observed with sirukumab 100 mg q2w versus placebo in Parts A (2.1 vs 0.6, p<0.001) and B (2.2 vs 1.1; p<0.001). The incidence of adverse events (AEs) was similar for sirukumab-treated and placebo-treated patients through week 12 in Part A (70.6% and 63.2%, respectively) and B (67.8% and 66.7%, respectively). Infections were the most common type of AE; one death occurred (Part B, sirukumab 100 mg q2w, brain aneurysm).

Conclusions Sirukumab-treated patients experienced improvements in the signs/symptoms of RA. Safety results through 38 weeks were consistent with other IL-6 inhibitors.

Trial registration number NCT00718718.

Via Krishan Maggon