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Abstract
Objectives No 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.
Methods Multicentre 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.
Results 110 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).
Conclusion Among 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 number NCT01782235.
- Sjogren's syndrome
- biological therapy
- cytokines
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Footnotes
Handling editor Josef S Smolen
Contributors All authors contributed to the study by their substantial contribution to the design of the study, acquisition of data and data interpretation. J-EG, LH and NM had access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read the manuscript. All individuals included in the Acknowledgements section gave their permission to the corresponding author, who confirms that such permission has been obtained in the Authorship Form.
Funding The study was sponsored by Hôpitaux Universitaires de Strasbourg. Roche Chugai provided tocilizumab and the placebo and a grant to fund the study but had no role in the study design, data collection, analysis, interpretation or manuscript preparation, revision or approval of the manuscript. The French patient’s association (Association Française du Gougerot-Sjögren et des Syndromes Secs, AFGS) gave a grant to fund the study.
Competing interests J-EG received honoraries and research grants from BMS and Pfizer, and honoraries from CSL Behring, Lilly, Janssen, UCB, Roche. All other authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years, no other relationships or activities that could appear to have influenced the submitted work.
Patient consent for publication Not required.
Ethics approval The protocol was reviewed and approved by the local institutional review board (Comité de Protection des Personnes Est IV; number: 12/30b). The study was conducted according to the current regulations of the International Conference on Harmonisation guidelines and the principles of the Declaration of Helsinki. Informed consent was obtained from all patients.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. Data can be requested from the scientific committee of the trial.
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