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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 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.

Background:Enthesitis is a key feature of peripheral Spondyloarthritis (SpA). Several pro-inflammatory cytokines including Interleukin-17 and Interleukin-23 are found within the enthesis (1). Dupilumab is a recombinant human monoclonal antibody that inhibits signalling of Interleukin-4 and Interleukin-13, approved for use in patients with moderate- to –severe atopic eczema. Here we describe a cohort of patients with severe atopic eczema who have developed a new peripheral SpA/ enthesitis after receiving Dupilumab.Objectives:To describe the clinical and imaging details of this cohort.Methods:All patients in St John’s Institute of Dermatology who exhibited new arthralgias on Dupilumab therapy were referred for assessment in Guy’s Rheumatology Department. These patients had a focussed history, examination, ultrasound and/or MRI of affected joints and entheseal sites.Results:To date we have seen 12 patients with a history of new inflammatory peripheral SpA type symptoms following onset of Dupilumab therapy. There were 7 males and 5 females all of whom have longstanding severe atopic Eczema. All patients had raised baseline IgE levels of mainly >10000. All patients exhibited a positive response to Dupilumab with a marked improvement in eczema as measured by the EASI score. All patients had normal inflammatory markers and negative immunological screening bloods. Musculoskeletal symptom onset was between 2 and 20 weeks after starting treatment. Typically, these patients had inflammatory symptoms affecting both the small joints and the entheseal sites. 2/12 patients developed inflammatory sounding spinal pain. 2/12 patients had ultrasound evidence of arthritis. 11/12 patients had radiological findings of enthesitis as seen on MRI or ultrasound (power doppler ultrasound signal). 9/12 patients were treated with non-steroidal anti-inflammatories with variable improvement.1 patient required no treatment and 1 patient received low dose prednisolone.Conclusion:In our centre approximately 200 patients have received Dupilumab. These musculoskeletal findings have not been reported previously in clinical trials. We hypothesise that the profound inhibition of IL- 4/13 may allow an inflammatory response at the enthesis presenting with a peripheral SpA pattern. IL-4 has been shown to suppress delayed type hypersensitivity reactions (DTHRs) and psoriasis in both human and mice studies (2). These findings and the demonstratation that IL-23 transcription and secretion can be suppressed by IL-4 with resultant reduction in Th17 function (3) may be key factors as to why a SpA type response is seen in certain subjects.References:[1]Bridgewood et al. Immunol Rev 2020 [Epub][2]Ghoreschi et al. Nat Med. 2003;9:40-6.[3]Guenova et al. PNAS. 2015;112:2163-8.Disclosure of Interests:Catherine Hughes Speakers bureau: Lilly, Bina Menon Speakers bureau: Novartis, Richard Woolf: None declared, Zena Willsmore: None declared, Catherine Smith: None declared, Andrew Pink: None declared, L Bruce Kirkham Grant/research support from: Eli Lilly Novartis, Consultant of: Eli Lilly Gilead Janssen Novartis

Behcet (1935) referred to the highly stigmatising and common inflammatory skin disease psoriasis (derived from the Greek word psora meaning itch) as “the antidote to a dermatologist's ego,” and although in some respects this is still true, major progress has been made in several important areas. Psoriasis occurs worldwide and affects about 2% of the population in the United Kingdom. A great deal is known about the genetic and immunological mechanisms underlying the pathogenesis of psoriasis. Some of the new biological treatments recently licensed for psoriasis have been developed as a result of this improved understanding, whereas others have been contributory—for example, the profound efficacy of agents that block the actions of cytokine tumour necrosis factor highlighted the key role of tumour necrosis factor in the disease's pathogenesis. Evidence is also accumulating that psoriasis is not just associated with skin disease. Epidemiological studies have shown an increased standardised mortality in patients with psoriasis, particularly related to cancer and heart disease. Clinically relevant psychological and psychiatric comorbidity are also common and potentially amenable to therapeutic intervention. This article presents an overview of these developments and their implications for clinical practice. ### Genetic factors Scans of the human genome reveal at least nine different loci with susceptibility to psoriasis (PSORS1-9). PSORS-1, a region of the major histocompatibility complex on chromosome 6p2, is the major genetic determinant of psoriasis, and accounts for up to 50% of genetic susceptibility to the disease,1 w1 although the definitive gene has not yet been identified. Several of the implicated loci are shared by other autoimmune and inflammatory diseases such as inflammatory bowel disease, type1 diabetes, multiple sclerosis, and atopic dermatitis, suggesting that similar mechanisms underlie many common genetically complex inflammatory diseases. #### Summary points Psoriasis is a common, disfiguring, and stigmatising skin disease associated with profound impaired quality of life The gene …