Sarilumab 200mg/1.14ml solution for injection pre-filled syringes

ObjectivesInfliximab, an anti-TNF agent, is used to treat sarcoidosis that does not respond to corticosteroids or second-line agents. The efficacy of other anti-TNF agents, non-TNF biologics and targeted synthetic therapies remains unclear. This study aims to evaluate the role of these therapies in the management of multisystem sarcoidosis.MethodsWe conducted a systematic literature search to identify trials of biological and targeted synthetic therapies in sarcoidosis. Meta-analyses examined %-predicted forced vital capacity (FVC), as mean change from baseline. Heterogeneity was measured using the I2 statistic. Vote counting based on the direction of effect, as recommended by the Cochrane network, was used to synthesise study estimates.ResultsThe search identified 6777 records. Sixteen studies met the inclusion criteria. These included 8 randomised control trials (RCTs) and 8 single-arm trials. Fourteen studies evaluated biologic therapies: infliximab (n=5), adalimumab (n=2), etanercept (n=2), golimumab (n=1), rituximab (n=1), anakinra (n=1), sarilumab (n=1), ustekinumab (n=1) and efzofitimod (n=1). Two trials assessed the targeted synthetic therapy tofacitinib. Risk of bias was high in five of eight RCTs. Meta-analysis of %-predicted FVC showed modest improvement with treatment (mean change: 4.79% (95% CI 1.22 to 8.35), driven by anti-TNF trials 5.70% (95% CI 1.61 to 9.78). Heterogeneity was substantial (I²=76.3%). In data synthesis using vote counting, infliximab, adalimumab, efzofitimod and tofacitinib demonstrated a positive direction of effect across all estimates, though improvements in several outcomes did not reach thresholds for minimal clinically important differences.ConclusionsMeta-analysis supports infliximab use in pulmonary sarcoidosis, although improvements in lung function are modest. There is limited but promising evidence for the use of adalimumab and tofacitinib in cutaneous disease and efzofitimob in pulmonary disease. Study interpretation is limited by small sample sizes and heterogeneity in study design and population.PROSPERO registration numberCRD42024599560.

Abstract licence: CC BY

Maria Gabriella Raimondo,1 Martina Biggioggero,1 Chiara Crotti,1 Andrea Becciolini,2 Ennio Giulio Favalli2 1Department of Clinical Sciences and Health Community, Division of Rheumatology, University of Milan, 2Department of Rheumatology, Gaetano Pini Institute, Milan, Italy Abstract: In recent years the use of biotechnological agents has drastically revolutionized the therapeutic approach and the progression of rheumatoid arthritis (RA). In particular, interleukin-6 (IL-6) has been demonstrated as a pivotal cytokine in the pathogenesis of the disease by contributing to both the innate and the adaptive immune system perturbation, and to the production of acute-phase proteins involved in the systemic expression of the disorder. The first marketed IL-6 blocker was tocilizumab, a humanized anti-IL-6 receptor (anti-IL-6R) monoclonal antibody. The successful use of tocilizumab in RA has encouraged the development of other biologic agents specifically targeting the IL-6 pathway, either directed against IL-6 cytokine (sirukumab, olokizumab, and clazakizumab) or IL-6 receptor (sarilumab). One Phase II and six Phase III randomized controlled trials demonstrated a broad efficacy of sarilumab across all RA patient subtypes, ranging from methotrexate (MTX) to tumor necrosis factor inhibitor insufficient responders. In particular, sarilumab as monotherapy demonstrated a clear head-to-head superiority over adalimumab in MTX-intolerant subjects. In addition, compared with tocilizumab, sarilumab showed a similar safety profile with significantly higher affinity and longer half-life, responsible for a reduction of the frequency of administration (every other week instead weekly). All these aspects may be important in defining the strategy for positioning sarilumab in the treatment algorithm of RA. Indeed, observational data coming from post-marketing real-life studies may provide crucial additional information for better understanding the role of sarilumab in the management of the disease. This review summarizes both the biological role of IL-6 in RA and the clinical data available on sarilumab as an alternative therapeutic option in RA patients. Keywords: rheumatoid arthritis, interleukin-6, sarilumab, monoclonal antibody, biologic drugs

Abstract licence: CC BY-NC 3.0