Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial

Abstract

ObjectivesNo immunomodulatory drug has been approved for primary Sjögren’s syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients with Sjögren’s syndrome-related systemic complications.MethodsMulticentre double-blind randomised placebo-controlled trial between 24 July 2013 and 16 July 2018, with a follow-up of 44 weeks, involving 17 referral centres. Inclusion criteria were primary Sjögren’s syndrome according to American European Consensus Group criteria and score ≥5 for the EULAR Sjögren’s Syndrome Disease activity Index (ESSDAI, score of systemic complications). Patients were randomised to receive either 6 monthly infusions of tocilizumab or placebo. The primary endpoint was response to treatment at week 24. Response to treatment was defined by the combination of (1) a decrease of at least 3 points in the ESSDAI, (2) no occurrence of moderate or severe activity in any new domain of the ESSDAI and (3) lack of worsening in physician’s global assessment on a Visual Numeric Scale ≥1/10, all as compared with enrolment.Results110 patients were randomised, 55 patients to tocilizumab (mean (SD) age: 50.9 (12.4) years; women: 98.2%) and 55 patients to placebo (54.8 (10.7) years; 90.9%). At 24 weeks, the proportion of patients meeting the primary endpoint was 52.7% (29/55) in the tocilizumab group and 63.6% (35/55) in the placebo group, for a difference of −11.4% (95% credible interval −30.6 to 9.0) (Pr[Toc >Pla]=0.14).ConclusionAmong patients with primary Sjögren’s syndrome, the use of tocilizumab did not improve systemic involvement and symptoms over 24 weeks of treatment compared with placebo.Trial registration numberNCT01782235.

Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview

“…Regarding IL-6 inhibition, as the IL-6 signaling is important for the IL-17 cells differentiation, an effect of tocilizumab on Th17 cells is probable. However, the results of a randomized placebo-controlled study showed that Tocilizumab had no impact on the main symptoms of SS, although improvements in joint involvement were observed ( 239 ).…”

Correspondence on ‘Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised controlled trial’

“…10 Since with a composite endpoint response needs to be achieved on multiple items, placebo response is expected to be lower, which is crucial to demonstrate treatment efficacy. In the tocilizumab RCT of Felten et al, 1 ESSDAI response rates were 53% in the tocilizumab and 64% in the placebo group. Clinical, patient-reported, gland-centred and immunological outcomes showed negative results, suggesting no beneficial treatment effect from tocilizumab.…”

“…We read with interest the correspondence related to the article 'Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial' in which possible explanations for negative findings in recent phase III randomised controlled trials (RCTs) for primary Sjögren's syndrome (pSS) are discussed, including the RCT with tocilizumab. [1][2][3] This is an important issue to raise, since there is still an unmet need for effective treatment in pSS.…”

Primary Sjögren’s Syndrome: A Retrospective Cohort Study of Burden of Illness in Sweden

“…The heterogeneous presentations of patients with pSS can make the disease difficult to diagnose and treat. There are currently no available immunomodulatory therapies that have proven efficacy in targeting the underlying pathway(s) of pSS [22] with neither conventional standard nor biologic disease-modifying antirheumatic drugs demonstrating robust or substantial efficacy in large studies [11,[23][24][25][26][27][28][29][30][31][32].…”