AB0785 EFFICACY OF BIOLOGIC AND TARGETED SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS IN THE TREATMENT OF SARCOIDOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: K. Bechman, K. He, A. Miracle, K. Biddle, J. Galloway
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sarcoidosis is a rare systemic inflammatory disorder of unknown aetiology, characterised by the formation of non-caseating granulomas. Clinical manifestations vary enormously, depending on the organ involved. Management can be challenging due to the suboptimal efficacy and toxic side effects associated with conventional treatments such as corticosteroids and second line immunosuppressants. Third-line therapies, including biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), have emerged as promising alternatives. <h3>Objectives:</h3> The aim of this systematic review was to examine the efficacy b/tsDMARDs in the treatment of sarcoidosis. Meta-analyses focused on i) studies meeting their primary outcome and ii) studies measuring change in forced vital capacity (FVC). <h3>Methods:</h3> A systematic search of the MEDLINE, EMBASE, and ClinicalTrials.gov databases were performed to identify placebo controlled and single arm studies reporting on the efficacy of b/tsDMARDs in sarcoidosis patients. Data were manually extracted. Study quality was assessed using the Cochrane risk-of-bias tool and the Newcastle-Ottawa Scale. Meta-analyses of primary outcome data from placebo-controlled trials were performed using random-effects models and reported as odds ratios (OR) with 95% confidence intervals (CI). Meta-analyses of change in FVC from placebo controlled and single arm studies were performed using fixed-effects models and reported as change in FVC % predicted with 95% CI. Heterogeneity was assessed using the I<sup>2</sup> statistic. <h3>Results:</h3> Seventeen studies were included, assessing 9 bDMARDs across 15 trials and one tsDMARD in two trials (Table 1). We found relatively abundant yet inconsistent support for infliximab; potential efficacy of tofacitinib, limited yet consistent support for adalimumab, rituximab and anakinra; inefficacy of golimumab, ustekinumab, and efzofitimod; and inconclusive results for sarilumab. Four randomised controlled trials (RCTs) were eligible for inclusion in the meta-analysis of studies meeting their primary outcome. Pooled estimates suggest no statistically significant difference between the number of patients meeting the primary outcome in the treatment groups compared to the control groups (OR: 1.03, 95% CI: 0.33-3.20) (Figure 1a). Three RCTs and three single-arm trials were eligible for inclusion in the meta-analysis of the change in FVC % predicted. There was a small and clinically non-significant increase in FVC% predicted from baseline following treatment (pooled change in FVC% predicted: 1.80, 95% CI: 0.26-3.34) (Figure 1b). <h3>Conclusion:</h3> b/tsDMARDs studies in sarcoidosis have demonstrated potential efficacy of infliximab, adalimumab, anakinra, rituximab, and tofacitinib. Meta-analyses of b/tsDMARDs placebo controlled trial data suggests an overall inefficacy in meeting studies primary outcomes, whilst pooled data from placebo controlled and single arm studies examining lung function has demonstrated a small and clinically non-significant increase in FVC%. Limited studies warrant caution in interpreting these findings. Further research involving larger sample sizes and a set of standardised outcome measures is imperative to substantiate these findings. <b>Table 1.</b> Characteristics of the included studies. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>