Executive summary: 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. 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. The most recent British Society for Rheumatology (BSR) guidelines for the treatment of PsA were published in 2012 [1] and focused 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 IL IL17, IL12/23, IL23 p19, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), phosphodiesterase-4 (PDE4) and Janus kinase (JAK) inhibition. To offer systematic and evidence-based recommendations to support UK clinicians in the prescription of bDMARD and tsDMARD therapies in adult patients with PsA. The guideline also includes guidance for managing those patients with extra-articular manifestations (uveitis and IBD), as well as those who smoke or are overweight. This guideline does not cover the use of conventional synthetic DMARDs, safety, use of biologics or tsDMARDs in pregnancy or juvenile idiopathic arthritis. We refer to the relevant BSR or other guideline recommended by the working group relating to these topics. For patients with psoriatic disease confined to the skin we recommend the British Association of Dermatologists guidelines for the management of psoriasis at https://www.bad.org.uk/healthcare-professionals/psoriasis. The guidelines have been developed to aid rheumatologists, dermatologists and other clinicians involved in the prescription of biologics and tsDMARDs for people with PsA. They 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 working party set up by the British Society for Rheumatology (BSR), including rheumatologists, dermatologists, an ophthalmologist, a gastroenterologist, a general practitioner, an epidemiologist, a specialist nurse and patient representatives. This guideline was developed in line with the British Society for Rheumatology’s guideline Protocol, which has National Institute for Health and Care Excellence (NICE) accreditation [2]. The evidence used to develop these guidelines was compiled from a systematic and comprehensive literature search, including electronic bibliographic databases (Medline and Embase) and the Cochrane Database of Systematic Reviews up to 10 December 2020. The GRADE method was used to assess the quality of evidence and the strength of recommendation. Recommendations were categorized as either strong (denoted by 1) or weak (denoted by 2), according to the balance between benefits, risks, burden and cost. The quality of evidence was categorized as either high (A), moderate (B) or low/very low (C) quantifying estimates of benefits or harm. A strong recommendation (to offer or not to offer) something, where the benefits clearly outweigh the risks (or vice versa) for nearly all patients, is denoted by the number 1 in the guideline. A conditional recommendation (to consider or not), is made either when the risks and benefits are more closely balanced or are more uncertain and are denoted by the number 2 in this guideline. GRADE recommends that where it is generally agreed by the medical community that certain principles of diagnosis and disease will do more good than harm (or vice versa), then these should be stated in terms of ‘good practice statements’. The ‘good practice statements’ within this guideline are not necessarily evidence-based; however, they are a description of generally accepted best medical practice agreed within our Guideline Working Group. A summary algorithm for the use of b/tsDMARDs in the treatment of individuals with PsA can be found in Fig. 1. Summary algorithm for the treatment of an individual with PsA with b/tsDMARDs Therapeutic decisions need to be individualized and should be based on shared-decision making between people with psoriatic arthritis and their clinicians (strength of agreement [SoA] 98%). All medication decisions in people with PsA should take into account: disease presentation with activity in the different domains below, previous medication use, associated conditions such as psoriasis, uveitis, and IBD, other comorbidities and patient preference (SoA 97%). When a range of clinically suitable and equivalent treatments are being considered by people with psoriatic arthritis and their clinicians, select the least expensive, taking into account administration costs, dosage, price per dose and commercial arrangements (SoA 88%). If people with PsA have an inadequate response to a b/tsDMARD, consider potential factors that could be addressed including: confirming correct diagnosis, adherence, pain due to other causes, drug levels and immunogenicity (SoA 95%). While discussions about treatments may be discussed with wider members of the rheumatology team, we suggest that commencing a bDMARD or tsDMARD for PsA remains a decision that should be made by a rheumatology consultant. In people with active psoriatic arthritis (defined as at least three tender and three swollen joints or those with fewer joints and either poor prognositic markers or severe disease impact defined as ≥2 domains involved, extraarticular involvement or impaired quality of life), with inadequate response or intolerance to one csDMARD, consider escalation to b/tsDMARDs (GRADE 2A, SoA 98%). In people with active peripheral psoriatic arthritis, with inadequate response or intolerance to csDMARDs, offer a bDMARD (TNFi, IL12/23i, IL-17i, IL-23i, CTLA4-Ig) or tsDMARD (JAKi, or PDE4i) (GRADE 1A, 94%). When selecting therapy, consider using TNFi, IL17i or upadacitinib (UPA) ahead of IL12/23i or IL23i ahead of PDE4i ahead of CTLA4-Ig (GRADE 2B, SoA 88%). A summary of the results from RCTs of biologic and targeted synthetic DMARDs in PsA is shown in Table 1. Summary of key information relating to bDMARDs and tsDMARDS in PsA Mixed population with some TNFi exposure. Data on subset with all data available and baseline BSA >3%. Data at 24 weeks from IMPACT2 study only. Week 12 data based on PALACE 2 and 3, week 24 data based on PALACE 1, all trials mixed population with TNF exposure. ABA: abatacept; ACR50: ACR 50% response; ADA: adalimumab; APR: apremilast; AxSpA: axial spondyloarthritis; CD: Crohn’s disease; CZP: certolizumab pegol; ETN: etanercept; GOL: golimumab; GUS: guselkumab; INF: infliximab; IXE: ixekizumab; MDA: minimal disease activity; PASI75: psoriasis area and severity index 75% response; PBO: placebo; SEC: secukinumab; TOFA: tofacitinib; UC: ulcerative colitis; UPAD: upadacitinib; UST: ustekinumab. Summary of key information relating to bDMARDs and tsDMARDS in PsA Mixed population with some TNFi exposure. Data on subset with all data available and baseline BSA >3%. Data at 24 weeks from IMPACT2 study only. Week 12 data based on PALACE 2 and 3, week 24 data based on PALACE 1, all trials mixed population with TNF exposure. ABA: abatacept; ACR50: ACR 50% response; ADA: adalimumab; APR: apremilast; AxSpA: axial spondyloarthritis; CD: Crohn’s disease; CZP: certolizumab pegol; ETN: etanercept; GOL: golimumab; GUS: guselkumab; INF: infliximab; IXE: ixekizumab; MDA: minimal disease activity; PASI75: psoriasis area and severity index 75% response; PBO: placebo; SEC: secukinumab; TOFA: tofacitinib; UC: ulcerative colitis; UPAD: upadacitinib; UST: ustekinumab. iii. In people with active psoriatic enthesitis, with inadequate response or intolerance to a csDMARD, offer any bDMARD (TNFi, IL12/23i, IL-17i, IL-23i) or tsDMARD (JAKi, or PDE4i) (GRADE 1A, SoA 91%). iv. In people with active psoriatic dactylitis, with inadequate response or intolerance to a csDMARD, offer any bDMARD (TNFi, IL12/23i, IL-17i, IL-23i) or tsDMARD (JAKi, or PDE4i) (GRADE 1A, SoA 92%). v. In people with active psoriatic axial disease, with inadequate response or intolerance to at least 2 NSAIDs, offer any TNFi or IL-17i or consider a JAKi (GRADE 1A, SoA 92%). vi. Where a person has associated conditions alongside their psoriatic arthritis, such as psoriasis, uveitis and/or IBD, a multidisciplinary and multispecialty approach should be taken for their care including timely discussions prior to systemic treatment changes. Be aware of other licensed indications and option for differential dosing of common medications in different indications to optimize doses for each individual (GRADE 1B, SoA 98%). vii. In the presence of psoriasis, offer concomitant topical therapy (in line with NICE CG 153) (GRADE 1A, SoA 96%). viii. In the presence of psoriasis and/or nail psoriasis, all currently licensed b/tsDMARDs can be offered but consider prioritizing therapies recommended use for psoriasis: monoclonal TNFi, IL-17i, IL-12/23i or IL-23i summarized in publication [3] (GRADE 1A, SoA 93%). ix. In the presence of significant psoriasis, be aware that IL-17i and IL23i have superior evidence of efficacy over TNFi [significant psoriasis is defined as extensive psoriasis (BSA ≥10 or PASI ≥10) or localized psoriasis associated with significant functional impairment and/or high levels of distress (for example severe nail disease or involvement at high-impact sites)] (GRADE 1A, 92%). x. In the presence of a mild relapse of anterior uveitis, follow standard treatment with concomitant topical therapy (GRADE 1A, SoA 94%). xi. In the presence of moderate to severe sight threatening uveitis or multiple recurrent relapses, consider adalimumab or another monoclonal TNFi (GRADE 1A, 97%). xii. Refer to the global consensus guideline [4] or NHS England guideline [5] for additional advice on management of uveitis (GRADE 1C, SoA 96%). xiii. In the presence of a mild or suspected relapse of IBD, discuss with gastroenterology as a first step (GRADE 1C, SoA 94%). xiv. In the presence of moderate to severe Crohn’s disease, offer any bDMARD (adalimumab, infliximab, certolizumab, ustekinumab) or consider IL-23i (GRADE 1A, SoA 93%). xv. In the presence of moderate to severe UC, offer any bDMARD (adalimumab, infliximab, golimumab, ustekinumab) or tsDMARD (tofacitinib) or consider upadacitinib (GRADE 1A, SoA 93%). xvi. Prior to prescription of an IL-17i, consider GI referral for people with un-investigated persistent lower GI symptoms or people with a strong family history of IBD (GRADE 2C, SoA 93%). xvii. Do not use IL-17i in people with active Crohns disease (GRADE 1B, SoA 88%). xviii. IBD is not an absolute contraindication to commencement of an IL17i; however, secukinumab and Ixekizumab are not recommended in individuals with IBD. Exercise caution and consult gastroenterology team before offering IL-17i to people with controlled UC or Crohn’s disease. If used, individuals and their clinicians should be regularly monitoring for symptoms compatible with IBD (GRADE 1C, SoA 89%). A treat-to-target strategy, whereby an individual’s disease activity is proactively measured and treatment escalated accordingly, should be offered to all people with psoriatic arthritis who require treatment (GRADE 1A, SoA 96%). The treat-to-target strategy should aim for remission or alternatively low disease activity, taking into account patient goals, associated conditions and co-morbidities, and non-inflammatory causes of pain (GRADE 1B, SoA 96%). In people with psoriatic arthritis who are on treatment and in a stable low disease activity state across disease domains and associated conditions, consider dose reduction or dose spacing of medication following shared decision making with the patient and in consultation with the other specialists involved in their care (GRADE 2B, SoA 98%). When considering treatment with biosimilars for people with PsA, refer to the British Society for Rheumatology 2018 factsheet on Biosimilars (GRADE 1C, SoA 96%). In people with active psoriatic arthritis beginning b/tsDMARDs, the routine use of concurrent csDMARDs is not required but concurrent csDMARDs may be required for the drug licence and may be considered to maximise effectiveness for skin disease, IBD or uveitis and/or to improve persistence with TNFi (GRADE 1A, SoA 97%). In people with active psoriatic arthritis, with inadequate response or intolerance to a b/tsDMARD, offer any of the current licensed b/tsDMARD treatments (GRADE 1A, SoA 94%). When selecting therapies, following an inadequate response or intolerance to a b/tsDMARD, consider the following (GRADE 2B, SoA 96%): the domains of disease relevant in that individual, previous medication use, and associated conditions such as psoriasis, uveitis, and IBD, as with first-line b/tsDMARDS; in people who have primary inefficacy to a b/tsDMARD, consider a different mode of action for the next treatment; and in people who have developed secondary inefficacy to a b/tsDMARD, consider drugs with the same mode of action first; however, all currently licenced b/tsDMARDS, without limit to previous lines of therapy and including those previously discontinued can be considered. People with PsA should have their height, weight and BMI recorded (GRADE 2B, SoA 94%). In people with PsA who are overweight or obese, offer weight loss support and signpost to relevant services to maximise response and long-term medication effectiveness of biologics and targeted synthetic DMARDs (GRADE 1A, SoA 98%). In people with PsA, treatment selection should not be affected by a person’s weight (GRADE 2C, SoA 88%). People with PsA should have their smoking status recorded (GRADE 2B, SoA 97%). In people with PsA who are smokers, signpost to smoking cessation support services to maximise treatment response, persistence and improve general health (GRADE 1A, SoA 99%). In people with PsA, treatment selection should not be affected by the person’s smoking status although doses should be adjusted appropriately (GRADE 2C, SoA 96%). This is the executive summary of ‘The 2022 British Society for Rheumatology guideline for the treatment of psoriatic arthritis with biologic and targeted synthetic DMARDS’. For the full guideline, please see https://doi.org/10.1093/rheumatology/keac295. We gratefully acknowledge the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the members of their Treatment Recommendations working group who shared extracted data on treatment RCTs for this project. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: L.C.C. has received honoraria for consultation and educational talks from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galapagos, Gilead, GSK, Janssen, Eli Lilly, Medac, Moonlake, Novartis, Pfizer and UCB. L.C.C. is also actively involved in studies evaluating new drugs for PsA; these were only included in the guideline if identified in the systematic literature review. W.T. has received research grant income from Eli Lilly and Janssen, as well as consultancy fees, speaker fees or financial support to attend conferences from Amgen, Eli Lilly, Janssen, Novartis, UCB. D.C. is the Chief Executive of Psoriasis and Psoriatic Arthritis Alliance. A.D. has acted as a consultant for Janssen, Novartis, Roche and AbbVie. A.D. is also the Director of the UCL Institute of Ophthalmology and has received funding from NIHR to start a trial on adalimumab in uveitis. A.F. has received educational support to attend conferences from or acted as a consultant or speaker for AbbVie, Almirall, Celgene, Eli Lilly, Leo Pharma, Novartis, Pfizer, Janssen and UCB. N.G. has participated in advisory boards for AbbVie, Eli Lilly, Janssen, Novartis and UCB, and is a trustee of British Psoriatic Arthritis Consortium Clinical Trials, working with Abbvie, Eli Lilly, Gilead and Novartis. P.H. has received grants and research support from Novartis, and honoraria or consultation fees from Pfizer, Eli Lilly, Janssen and Celgene. D.J. has acted as a Principal/Chief Investigator on industry-sponsored clinical trials, and has received research, development and/or education grants from Pfizer, AbbVie, Eli Lilly, Biogen, GSK, Celgene, Novartis, Gilead, UCB, Janssen, Celltrion and Sandoz. Education grants have been paid to Spondyloarthritis Training and Education (SPATE) UK Ltd, of which D.J. is a Co-Director. D.J. has received speaker fees for advisory boards/consultancy fees from Novartis, Eli Lilly, Gilead, Biogen, UCB, Janssen, AbbVie, Roche, Pfizer and Sandoz. D.J. is also a trustee to Cambridge Arthritis Research Endeavour (CARE) and British Psoriatic Arthritis Consortium (Brit-PACT), as well as a Research Steering Committee member for GRAPPA and a member of the Association for Assessment of Axial Spondyloarthritis (ASAS). G.J. is Chief Investigator of the British Society for Rheumatology Psoriatic Arthritis Register, for which the University of Aberdeen has received research grants from the British Society for Rheumatology and, in turn, Amgen. The University of Aberdeen has also received grant income from GSK for a project on which G.J. is a co-investigator. S.K. has received honoraria from Novartis and Celltrium. T.R. has received speaker or consultancy fees from AbbVie, Janssen, Novartis and UCB, as well as research grants from AbbVie, Amgen, BMS, Boehringer-Ingelheim, GSK, Janssen, Lilly, Novartis and UCB. T.R. is a trustee and executive steering group member for Brit-PACT and BRITSpA and is Chair of the Versus Arthritis Adult Inflammatory Arthritis Research Advisory Group. C.S. is GSTT-PI/co-investigator on clinical trial work or studies sponsored or supported by AbbVie, GSK, Janssen, Novartis, Pfizer, Regeneron, Roche, Boehringer Ingleheim, NIHR and SOBI. C.S. also works on PSORT and BIOMAP, which have multiple industry partners including: AbbVie, Sanquin, Qiagen, Pfizer, Novartis, MedImmune, Janssen, Celgene, Sanofi, LEO Pharma, Boehringer Ingleheim and UBC (list not exhaustive as partners change, please see psort.org and https://www.biomap-imi.eu/ for current information). C.S. is also a NICE expert advisor on interventions in psoriasis and eczema for STAs; Chair and committee member for multiple guidelines from the British Association of Dermatologists; member of the International Psoriasis Council. L.C.C. is an NIHR Clinician Scientist funded by a National Institute for Health Research Clinician Scientist award. The work was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The remaining authors have declared no conflicts of interest. All relevant data produced during the guideline development process are presented in the guideline or in the accompanying supplementary material.

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