Long-Term Safety of Sarilumab in Rheumatoid Arthritis

An Integrated Analysis With Up to 7 Years' Follow-Up

Roy Fleischmann; Mark C. Genovese; Yong Lin; Gregory St John; Désirée van der Heijde; Sheldon Wang; Juan Jose Gomez-Reino; Jose Antonio Maldonado-Cocco; Marina Stanislav; Alan J. Kivitz; Gerd R. Burmester


Rheumatology. 2020;59(2):292-302. 

In This Article

Abstract and Introduction


Objective: Sarilumab is a human monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor-α. We assessed the long-term safety of sarilumab in patients from eight clinical trials and their open-label extensions.

Methods: Data were pooled from patients with rheumatoid arthritis who received at least one dose of sarilumab in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; combination group) or as monotherapy (monotherapy group). Treatment-emergent adverse events (AEs) and AEs and laboratory values of special interest were assessed.

Results: 2887 patients received sarilumab in combination with csDMARDs and 471 patients received sarilumab monotherapy, with mean exposure of 2.8 years and 1.7 years, maximum exposure 7.3 and 3.5 years, and cumulative AE observation period of 8188 and 812 patient-years, respectively. Incidence rates per 100 patient-years in the combination and monotherapy groups, respectively, were 9.4 and 6.7 for serious AEs, 3.7 and 1.0 for serious infections, 0.6 and 0.5 for herpes zoster (no cases were disseminated), 0.1 and 0 for gastrointestinal perforations, 0.5 and 0.2 for major adverse cardiovascular events, and 0.7 and 0.6 for malignancy. Absolute neutrophil counts <1000 cells/mm3 were recorded in 13% and 15% of patients, respectively. Neutropenia was not associated with increased risk of infection or serious infection. Analysis by 6-month interval showed no signal for increased rate of any AE over time.

Conclusion: The long-term safety profile of sarilumab, either in combination with csDMARDs or as monotherapy, remained stable and consistent with the anticipated profile of a molecule that inhibits IL6 signalling.


IL-6 is a pleiotropic cytokine that plays a role in metabolic, homeostatic and regenerative processes.[1] IL-6 levels increase in response to infection or injury, promoting and coordinating pro-inflammatory activities. In autoimmune conditions such as RA, persistently elevated IL-6 levels can contribute to chronic inflammation and disease progression.[2]

Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor (IL-6R)-α to inhibit IL-6 cis- and trans-signalling.[3] Sarilumab is approved for the treatment of adults with moderately to severely active RA.[3] The efficacy and tolerability of sarilumab administered subcutaneously as monotherapy and in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have been demonstrated in active-comparator- and placebo-controlled phase III trials in adults with RA.[4–6] Long-term data on sarilumab as monotherapy and in combination with csDMARDs are being collected in patients with RA originally enrolled in eight trials, including those who continued into extension trials.[4–11]

The aim of this post hoc analysis, the first integrated safety report of sarilumab in patients with RA, including up to 7.3 years of sarilumab exposure in combination with csDMARDs and up to 3.5 years as monotherapy, was to provide precise adverse event (AE) incidence rates (IRs) and to investigate changes in IRs over time for AEs of special interest (AESIs).