AB0649 INFECTION PROFILE OF IMMUNE-MODULATORY DRUGS USED IN AUTOIMMUNE DISEASES: ANALYSIS OF SUMMARY OF PRODUCT CHARACTERISTIC DATA
Authors: M. Dey, K. Bechman, C. Smith, A. Cope, E. Nikiphorou, J. Galloway
Journal: Annals of the Rheumatic Diseases (2021)

Background: The number of immune-modulatory drugs used to treat immune-mediated inflammatory diseases (IMIDs) has exponentially increased in recent decades. While effective in controlling disease, serious infection remains a concern. Accurate information on immune-modulatory drugs, including infections, is required to guide prescribing decisions. The “summary of product characteristics” (SmPC) by the European Medicines Agency (EMA) provides a useful repository of information on adverse events e.g. infections, from clinical trials and post-marketing pharmacovigilance (1). To date, no comparison has been undertaken on reported infection frequencies across SmPCs for immune-modulators. Objectives: To compare infection frequency, site and type across the most commonly-prescribed immune-modulatory drugs used to treat IMIDs, using information provided by SmPCs. Methods: A drug was included if licensed in Europe for treatment of one of the following: rheumatoid arthritis, axial spondyloarthritis, connective tissue disease, autoimmune vasculitis, autoinflammatory syndromes, inflammatory bowel disease (Crohn’s and ulcerative colitis), psoriasis, multiple sclerosis and other rarer conditions. The Electronic Medicines Compendium (EMC) was searched for commonly prescribed immune-modulatory drugs used for the above indications. SmPC documents were manually searched for information on infection frequency, extracted from sections 4.4 and 4.8. Infection frequency was recorded as per convention in the SmPC: very common (≥1/10); common (≥1/100 to &lt;1/10); uncommon (≥1/1,000 to &lt;1/100); rare (≥1/10,000 to &lt;1/1,000); very rare (&lt;1/10,000) (1), for each drug. Information was further extracted on infection site (e.g. respiratory, skin etc), type (e.g. bacterial, viral etc) and individual pathogenic organisms. 25% of included SmPCs were screened and extracted by a second reviewer. Disagreements were resolved with input from a third reviewer. Results: In total, 39 drugs were included, used across 20 indications: nine conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), six targeted synthetic DMARDs (tsDMARDs; four Janus kinase [JAK] inhibitors, two sphingosine 1-phosphate receptor modulators) and 24 biologic DMARDs (17 cytokine-targeted; seven cell-targeted). Twelve sites of infection were recorded. Minimal or no site information was available for most csDMARDs and siponimod, certolizumab pegol and rituximab. The most common sites of infection are listed by drug group in Figure 1. Upper respiratory tract was the most common site, especially with bDMARDs. Lower respiratory, ear/nose/throat (including sinusitis) and urinary tract infections were moderately common, with clustering within drug groups. No drugs reported risk of cardiac infections; the eye, musculoskeletal, neurological, oral and reproductive sites were the least commonly-reported sites of infection. Infection data for 27 distinct pathogens were recorded, the majority viruses, especially with bDMARD use. Herpes simplex and zoster were the most frequently listed (mainly with bDMARDs and tsDMARDs), followed by influenza. Common non-viral causes of infection were candida and tinea species. Variable or absent reporting was noted for opportunistic infections (e.g. tuberculosis and fungi) and certain high-prevalence viruses e.g. Epstein-Barr. Conclusion: The SmPC literature reports differences in infection risk, by site and pathogen, between immune-modulatory drugs. The findings can be used to visualise differences and aid treatment decisions. However, some of the patterns we have shown lack face-validity to clinicians familiar with real-world safety data. The data fail to capture risk of rare infections, are likely skewed by trial selection criteria, varying number of trials per drug and quirks of individual study-reporting methodologies. The findings highlight the need for robust post-marketing pharmacovigilance studies. References: [1]A Guideline on Summary of Product Characteristics Module 1.3. 2008. Disclosure of Interests: None declared.