Abstract

Objectives Infliximab, 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. Methods We 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. Results The 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. Conclusions Meta-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 number CRD42024599560