The 2022 British Society for Rheumatology guideline for the treatment of psoriatic arthritis with biologic and targeted synthetic DMARDs

PsA is a chronic, inflammatory, musculoskeletal disease affecting approximately one quarter of people with the skin condition psoriasis [1, 2]. PsA is a highly heterogeneous disease, encompassing diverse musculoskeletal manifestations or ‘domains’ resulting from disease activity in different tissues. These include peripheral arthritis, spondylitis (axial inflammation), dactylitis (inflammation of the whole digit) and enthesitis (inflammation where a tendon, ligament or joint capsule insert to the bone). Unlike RA, there is a significant variability in clinical presentation of PsA. Individuals with PsA may have different domains involved and drugs have different levels of effectiveness on each domain. It is therefore essential that clinical guidelines for the treatment selection in PsA include disease phenotype and differential effect of medication. PsA is a potentially debilitating and destructive disease, with half of people developing irreversible joint damage within 2 years [3]. This results in significant functional limitations, depression and anxiety, as well as negatively impacting on education, work capacity and social participation [4–8]. Furthermore, PsA is associated with extra-articular manifestations, including inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and uveitis. In addition, metabolic syndrome (obesity, diabetes, hypertension, hyperlipidaemia, fatty liver disease) and cardiovascular disease are more common compared with the prevalence in the general population [7, 9, 10]. All of these factors may influence treatment selection [11] and potentially modifiable risk factors, such as obesity and smoking, which can impact therapeutic response and prognosis, should be addressed within the management plan. There is strong evidence that a treat-to-target (T2T) approach to PsA management, aiming for remission or low disease activity, results in better clinical, radiographic and patient-reported outcomes [12, 13]. Significant advances in therapeutic options available for PsA now mean a target of remission is an achievable goal. Despite PsA being a highly heterogeneous disease, most physicians apply the same step-up therapy to all people with peripheral arthritis, owing to the lack of comparative evidence. Initially a single conventional systemic disease-modifying anti-rheumatic drug (csDMARD) is used, with methotrexate typically being prescribed first-line. This is followed by use of an alternative single csDMARD or combinations of csDMARDs, prior to biologic use if the previous treatment step is unsuccessful [11, 14]. Up to 50% of people with PsA require biologic or targeted synthetic (b/ts)DMARD therapy [15] and treatment in the UK is governed by specific agencies, owing to the higher cost of these drugs. This includes recommendations in England from the National Institute for Health and Care Excellence (NICE) criteria and in Scotland from the Scottish Medicines Consortium (SMC). In addition, non-steroidal anti-inflammatory drugs and local corticosteroids are frequently used, which although not optimal for long-term use, do offer quick, short-term symptomatic relief, while DMARDs take effect. In practice, biologics require use for a minimum of 12 (e.g. TNFi) or 16 weeks (e.g. IL-17Ai), before response can be evaluated [16]. Unfortunately, a proportion of people do not respond to the first-line drug chosen (primary non-response), while other people respond well initially, but subsequently lose response (secondary non-response). For these reasons, as well as adverse events encountered by some people, switching therapy is required to achieve and maintain treatment targets. The last British Society for Rheumatology (BSR) guideline for the treatment of PsA was published in 2012 [12] and focussed specifically on TNF inhibitors as they were the only biologic DMARDs (bDMARDs) available. Since that time, there have been significant advances in therapeutic options available for PsA and drugs with different modes of action are now available, including IL17, IL12/23, IL23 p19, Cytotoxic T-lymphocyte-Associated antigen 4 (CTLA4-Ig), Phosphodiesterase-4 (PDE4) and Janus kinase (JAK) inhibition (i). We recognize existing high-quality international treatment recommendations, which include those written by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in 2021, EULAR in 2020 and American College of Rheumatology in 2018 [13, 17, 18]. However, these are generic to many international health settings and do not provide specific guidance for the UK, taking account of the healthcare system and prescribing restrictions. This guideline aims to look at the evidence beyond current NICE technology appraisals and to provide advice for the management of people with PsA. This guideline offers systematic and evidence-based recommendations to support UK clinicians in the prescription of bDMARD and tsDMARD therapies in adults with PsA. The guideline also includes guidance for managing those patients with extra-articular manifestations [uveitis and inflammatory bowel disease (IBD)], as well as those who smoke or are overweight. The guideline provides a stepwise management plan giving clear advice on treatment, including drug eligibility, sequencing, switching and treatment strategy. This guideline complements existing BSR guidelines and therefore does not include: detailed assessment of the safety of bDMARDs; biologic or tsDMARD therapies for juvenile idiopathic arthritis; use of csDMARDs in PsA; use of biologics or tsDMARDs in pregnancy; or biologic or tsDMARD therapies for adults with psoriatic disease confined to the skin only (in this situation, please refer to BAD guidelines for management of psoriasis at https://www.bad.org.uk/healthcare-professionals/psoriasis). The guideline has been developed to provide assistance to rheumatologists, dermatologists and other clinicians involved in the prescription of biologics and tsDMARDs for people with PsA. The guideline will also assist specialist nurses and allied health professionals (AHPs) in the assessment of treatment response, drug sequencing and switching and provide information to people with PsA who are receiving or moving towards biologic or tsDMARD therapy. The guideline has been developed by a multidisciplinary guideline working group (GWG) set up by BSR, including rheumatologists, dermatologists, an ophthalmologist, a gastroenterologist, a general practitioner, an epidemiologist, a specialist nurse and patient representatives. Any conflicts of interest among the GWG were fully declared. Details of members of this working party and their declared conflicts of interest are included at the end of this article and are available on the BSR website. The guideline was presented for comment at the BSR Annual Meeting in 2022 and was available for open consultation on the BSR website for a month prior to submission for publication. Opinions of key stakeholders, including members of the BSR, and Primary Care Rheumatology and Musculoskeletal Medicine Society (PCRMM), as well as patient members of the Psoriasis and Psoriatic Arthritis Alliance (PAPAA), were also sought. This guideline and recommendations were developed in line with BSR's Guidelines Protocol [19], which has National Institute for Health and Care Excellence (NICE) accreditation. The guideline and recommendations were underpinned with a systematic literature review. The evidence used to develop this guideline was compiled from a systematic literature review (SLR), including electronic bibliographic databases (Medline and Embase) and the Cochrane Database of Systematic Reviews up to 10 December 2020. Key terms for the search were the following: MeSH terms arthritis, psoriatic, psoriatic arthritis, psoriasis and arthritis in combination (independently) with biologic therapy mode of action, targeted synthetic mode of action or any biologic or tsDMARD drug name. Inclusion criteria for review were clinical outcomes in adults with PsA, published in English or in languages other than English with an English translation available. All titles and abstracts were screened by the BSR systematic literature reviewer and full papers of relevant material were obtained. In addition, data extraction and quality assessment undertaken by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) [20] was utilized to aid in the completion of this SLR. Reviews of the articles included were conducted to establish current evidence for the following topics: efficacy of TNF inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, IL-17 inhibitors, abatacept, apremilast or JAK inhibitors in different disease domains (peripheral arthritis, axial disease, as well as extra-articular and inflammatory bowel the clinical effectiveness of a treat-to-target the impact of bDMARD or tsDMARD and in switching to a use of csDMARDs, efficacy of biologic and tsDMARD therapies in people who are or smoke and the clinical of and in adults with PsA. 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