The 2025 British Society for Rheumatology guideline for the treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs

Axial spondyloarthritis (axSpA) is a chronic inflammatory condition that predominantly affects the spine and sacroiliac joints [1]. It can also involve peripheral joints and entheses, and extra-musculoskeletal manifestations (EMMs) such as acute anterior uveitis, psoriasis and IBD. Symptoms of axSpA typically begin in early adulthood but diagnosis can often take several years [2]. Chronic inflammatory pain and stiffness are well recognized as having adverse effects on quality of life, social participation and mental health [3–5]. Pharmacological management has advanced considerably since the previous BSR axSpA guideline [6] to incorporate new classes of biologic DMARDs (bDMARDs, including biosimilars), targeted synthetic DMARDs (tsDMARDs) and treatment strategies such as drug tapering. Therapeutic options for treating EMMs as index conditions have similarly evolved. The increasingly complex therapeutic landscape, with varying efficacy and safety of drugs for each disease manifestation, forms the context in which we aimed to update the BSR guideline for the treatment of axSpA with b/tsDMARDs. The key questions that the guideline sought to answer were published in the guideline scope [7], including the effectiveness and safety of targeted therapies; switching, combining, tapering or withdrawing targeted therapies; and treating to target. The guideline applies only to adults with axSpA. For brevity, we refer to b/tsDMARDs as “targeted therapies” throughout. This guideline is for health professionals in the UK who directly care for adults with axSpA (including but not limited to rheumatologists, rheumatology specialist nurses, allied health professionals, rheumatology specialty trainees, pharmacists), people living with axSpA and other stakeholders. NSAIDs, glucocorticoids and conventional synthetic DMARDs. Treatment of enthesitis/spondylitis-related juvenile idiopathic arthritis. Axial disease in psoriatic arthritis [8]. Safety of targeted therapies [9] or their use in pregnancy [10]. Health economic considerations. The guideline was developed by a multidisciplinary guideline working group (GWG), comprising and reflecting the views of individuals with lived experience of axSpA, rheumatologists, an ophthalmologist, a dermatologist, a gastroenterologist, a general practitioner, an epidemiologist, a specialist nurse, a consultant physiotherapist, a specialist pharmacist and the Chief Executive Office (CEO) of the patient-focused charity National Axial Spondyloarthritis Society (NASS). Drafting of the overarching principles was led by authors with lived experience of axSpA. Details of the GWG and their declared conflicts of interest are included at the end of this article and are available on the BSR website. The guideline was available for public consultation on the BSR website for a month prior to publication and was reviewed by the BSR Guideline Steering Group and external expert peer reviewers. This guideline was developed in accordance with the BSR Creating Guidelines Protocol (v5.4). The guideline and recommendations were underpinned by a systematic literature review. The full methodology and evidence tables are provided in Supplementary Data S1, available at Rheumatology online. The literature search was informed by the guideline scope [7] and registered in advance (PROSPERO: CRD42023437846). A literature review specialist (NC) performed searches across two databases (MEDLINE, EMBASE) and The Cochrane Library without language restriction, covering the period between 30th June 2014 (review date for the previous version of the guideline) and 17th April 2023. Full search details are provided in Supplementary Data S2. Eligibility criteria were agreed for randomized controlled trials (RCTs, for efficacy and safety) and observational designs (safety only). For observational evidence, only representative multi-site cohort studies or studies conducted using disease registries or electronic health record data were considered eligible. Other study designs, including cross-sectional studies, case-control designs, case series and other publication types (editorials, commentaries, trial protocols, letters, trials registry records and study protocols) were excluded, as well as full papers in any language other than English without an English translation. A detailed description of inclusion and exclusion criteria and a PRISMA flow diagram are provided in Supplementary Data S3 and S4, available at Rheumatology online, respectively. Two reviewers independently screened the first 10% of titles to ensure good agreement. For the remaining 90%, one reviewer screened titles, excluding studies that were clearly irrelevant. Abstracts, and then full texts were screened against eligibility criteria by one reviewer, with up to 20% double screened by a second reviewer to ensure accuracy. Any disagreements were resolved by a third reviewer. A standardized data extraction form was developed, piloted and used to collect data for analysis. Data were collected on country, study design, characteristics of the study population (including radiographic or non-radiographic axSpA and the presence of comorbidities and EMMs), intervention characteristics and efficacy and safety outcomes. Cochrane risk of bias tool [11] was used to assess risk of bias for RCTs and controlled clinical trials. For cohort designs, relevant bias domains were used from the ROBINS-I tool for assessing risk of bias in non-randomized intervention studies [12]. Data extraction and risk of bias assessment were undertaken by one reviewer and independently checked by a second for correctness and consistency. Disagreements were resolved by consulting a third reviewer if necessary. Evidence tables were prepared for each guideline question (Supplementary Data S1, available at Rheumatology online). GRADE [13] was used to summarize certainty in the evidence for each outcome across studies for each guideline question, separately for RCTs and observational studies, and separately for each drug category, and efficacy or safety outcome. As this was an update of an existing guideline, GRADE was applied to evidence identified from the update searches only (2014–2023), so does not reflect all evidence available for each intervention. Quality of evidence for each outcome was graded where A represents high, B moderate and C low/very low quality of evidence. “High quality” suggest that further research is very unlikely to change the confidence in the effect estimate (e.g. from well-performed RCTs or observational studies). Evidence was downgraded to moderate, low or very low based on concerns related to study design, risk of bias, inconsistency, indirectness (applicability) or imprecision. “Moderate quality” suggests that further research is likely to have an important impact on the confidence in the effect estimate and may change the estimate (e.g. from RCTs with important limitations, or from other study designs with special strength). “Low or very low quality” suggests that further research is very likely to have an important impact on confidence in the effect estimate and is likely to change the estimate (e.g. observational studies or RCTs with very serious limitations). Each recommendation was evaluated by all members of the GWG and subjected to a vote relating to strength of agreement (SoA) on a scale of 1 (total disagreement) to 100 (total agreement). The strength of agreement for each recommendation is presented as the mean of the GWG’s individual ratings, expressed as a percentage. Anonymized votes are shown in Supplementary Data S5, available at Rheumatology online. A rating of 1 (strong) is given where the GWG feels that benefits clearly outweigh the risks; 2 (conditional) when risks and benefits are more closely balanced or more uncertain. The recommendation statements are presented at the beginning of each section, accompanied by the strength of recommendation, quality of supporting evidence and strength of agreement in parentheses. This guideline is planned for update in 5 years. The primary goal of treatment for people living with axSpA is to enable them to lead healthy and productive lives by optimizing health-related quality of life through comprehensive management of all disease manifestations, prevention of structural damage, preservation of physical function, work productivity and social participation (SoA 99%). Management decisions should be developed in partnership with the individual living with axSpA based on their needs and priorities, within the available resources (SoA 99%). Management should involve a multidisciplinary team coordinated by a rheumatologist, utilizing a holistic approach that and (SoA overarching recommendations reflect and of expert The of treatment is to health-related quality of life by the living with axSpA at the of care and is to enable in The to or change targeted should be by the consultant and in partnership with the with axSpA, individual needs and to a healthy and productive Treatment should be reviewed to ensure and to the with axSpA. management and peripheral EMMs and the presence of holistic management should targeted that people with axSpA may disease manifestations of EMMs should be coordinated by the specialty the with the and for each The of therapeutic options for axSpA limited with other inflammatory the context of axSpA, EMMs without targeted where and Management of comorbidities should an multidisciplinary team approach (e.g. review of and clinical for mental in with primary to targeted therapies should not the on is the scope of this guideline to recommendations for are for the holistic approach to and living well with axSpA. and strategies should at the the of The GWG the of the and are for axSpA therapies have a evidence but all forms of physical are likely to as well as general health and are well in axSpA management and are for who therapies are important to the of mental health people with axSpA and can from to clinical as of the people with axSpA should be to their condition through including to resources for and or are for people with axSpA who have not and conventional management The targeted therapies for axSpA in the UK and relevant biosimilars), and and are not for non-radiographic axSpA. targeted therapies have an of efficacy and safety in axSpA RCTs (Supplementary Data S1, available at Rheumatology online). is evidence to one or drug in of efficacy for The to to targeted therapies and the of should be with the with axSpA, comorbidities and EMMs in 1 and in all people with axSpA structural on observational studies have shown that (e.g. with or have risk and of radiographic adverse should be considered as of when targeted evidence for the effect of therapies on radiographic is observational literature suggests that targeted therapies are more likely to radiographic with disease should be by the treating in the context of diagnosis and inflammatory disease by such as the Axial Spondyloarthritis and pain For the of to targeted disease should be use of and conventional and the diagnosis and inflammatory disease The diagnosis of axSpA should be by a consultant rheumatologist, and and non-radiographic axSpA with of on diagnosis are the scope of this the GWG that the of Spondyloarthritis Society criteria should not be used for diagnosis the general individuals for not axSpA and inflammatory on can be (e.g. the The to be balanced against the for The to should be agreed with the with axSpA, than based on disease of disease should be at the of treatment and at each The GWG using the and pain for assessing disease rating scale by scale and pain are included in recommendations to their use in clinical their that can be by such as comorbidities is the only shown to with radiographic and is included in all clinical trials in axSpA. of disease using or when the treatment For the GWG inclusion of in clinical diagnosis and assessing inflammatory disease can be is the of such as for and for peripheral manifestations may be recommendations have provided by the Society for Spondyloarthritis and and not be to targeted therapies should be using (e.g. and if treatment is The of to targeted therapies should of the diagnosis and the of inflammatory disease is important to assess the and the of assessment of disease should be holistic and but not disease The to should be between the with axSpA and the treating Treatment should be evaluated at a of assessing to and and The axSpA guideline For the guideline, the and of were from the public were that with The GWG that care can be with the recommendation be to that is and The GWG that the and of can be based on individual but should be reviewed at each to ensure or may be considered if the condition is and the with axSpA has and to a rheumatology or to with the clinical team if necessary. should not typically a or and in pain to be the of treatment can be by the presence of for more such as and pain is not with radiographic disease disease and criteria are to in and change disease use of is by and For the GWG that incorporate A of represents a important using any should are related to may to and domains of may to for As in recommendation of the spine and sacroiliac joints may to assess and other of axSpA is and should to the when is primary to targeted targeted is for individuals with disease who not or to the targeted 99%). As with overarching and treatment decisions for treatment should be and agreed with the with axSpA. is evidence to a of targeted therapies in the case of treatment in axSpA. are as by are people with to a second has shown in observational studies not to be so than the first The efficacy of in with has in RCTs The efficacy of in and in or has also shown in to a second is in axSpA with primary to the first with who of It is as in other inflammatory that people with axSpA who have primary to one are more likely to to a drug with a of from a drug to is not when is to the the context of diagnosis and inflammatory disease the GWG suggests that should not be a to the of therapies that any individual can This should of new therapies as Evidence for the safety and effectiveness of in axSpA is and represents an important research axSpA, observational evidence is limited to within the where the across and across of an important of were to up to the in the case of the presence of or uveitis, a is therapies with other of A of is not an to therapies with other of new in the context of axSpA, decisions to change treatment should be with an where the of and to anterior is the that can in up to a of people with axSpA accordance with new of should be by an within The of can from to or For or uveitis, the to a targeted should be between rheumatology and as of an can be with and of effects (e.g. and are for the treatment of anterior in axSpA targeted therapies are for this condition is for or evidence suggests that and may be at than to trial data not suggest that are for A of axSpA trial data published the full literature search that may be to for A of axSpA RCTs that all targeted therapies are likely to or in individuals with axSpA on or the of should be considered in consultation with an and are in the presence of psoriasis (e.g. or psoriasis at with or impact (e.g. or in with a people with axSpA, psoriasis has a of and is typically as For can be to and by the to people with axSpA but controlled management should be with a and may not a change in targeted For and therapies may axSpA and psoriasis are for targeted of psoriasis can be in of was to for but of or is used and are not for detailed psoriasis assessment (e.g. and in rheumatology may be the GWG using at one for assessing and For can be using the where the of their people with psoriasis who axSpA, or in people with where targeted therapies have led by decisions to should that therapies used in psoriasis have effect for (e.g. or other of have (e.g. or are likely to have therapeutic not for axSpA. with should be by a gastroenterologist, targeted therapies the presence of or are should not be 99%). A of is not an to or with of (including disease and should be to a or an targeted can be a tool for with for can be to use which should be when The of people with axSpA is can of axSpA including use and of targeted and can and treatment decisions should be in with where axSpA, may be by without a change in targeted or are in people with axSpA and where advanced therapies are should not be in people with as may in the clinical trial of in disease the limited of drug classes for axSpA, can be considered in the context of when other options are but the of risk and in should be considered with from is individuals and their should for with IBD. where is the use of targeted treatment decisions should the that therapies (e.g. or for treatment of Treatment should to agreed with the individual living with axSpA, using that comorbidities and inflammatory disease 99%). is with radiographic the trial of treating to in axSpA not primary outcome in Health or the of all were in the are to in the context of an may be for not the primary end (e.g. care than in is evidence to treating to an target. treating to in the trial through a of without This is an important and options for disease only classes of targeted therapies and The GWG as with the decisions to or therapeutic should be agreed with the with axSpA and not based on disease Treatment should the of available therapeutic adverse for disease and treatment and of inflammatory disease comorbidities or (e.g. and and general are all with axSpA disease of inflammatory disease such as and pain of targeted therapies should be considered for individuals who have of targeted therapies in the context of is not 99%). all have tapering without the in was not to for in and non-radiographic axSpA, with a risk of was in the risk of adverse trials were not to with axSpA in should be therapeutic with the agreed between the with axSpA and the but can be as low disease or for at is typically by which the of is an use of of targeted therapies in was in several RCTs of and one of were in with or tapering For of who the trial and not all were to inflammatory to is considered of axSpA such and are are likely without disease of targeted therapies is not people with axSpA, informed with trial may to and should be with to clinical review when of the evidence for targeted therapies across extra-musculoskeletal manifestations This is as a with the of characteristics data to prevention of acute anterior or to disease of each extra-musculoskeletal The of a of efficacy across each not not is a of evidence for or is evidence supporting a of for applies to and where has efficacy for all EMMs with The risk of and and is in than in observational was not to in a of but is unlikely to be directly to be considered for axSpA, review. is for in the and but not in the evidence is for but are studies has evidence of efficacy for psoriasis but is not evidence is for for is not for non-radiographic axSpA. is for but not for axSpA. to of RCTs published the literature search are likely to likely to for are not in but be considered for axSpA if is review. of and in of is available for but not non-radiographic axSpA. is to for psoriasis but of in psoriasis of axSpA trial data published the literature search the of with but is not for Evidence for the safety of in is is not for non-radiographic axSpA. has evidence of efficacy for psoriasis but is not as a group are likely to for to of was not to in a trial of has evidence of efficacy for psoriasis but is not as a group are likely to for to of of the evidence for targeted therapies across extra-musculoskeletal manifestations This is as a with the of characteristics data to prevention of acute anterior or to disease of each extra-musculoskeletal The of a of efficacy across each not not is a of evidence for or is evidence supporting a of for applies to and where has efficacy for all EMMs with The risk of and and is in than in observational was not to in a of but is unlikely to be directly to be considered for axSpA, review. is for in the and but not in the evidence is for but are studies has evidence of efficacy for psoriasis but is not evidence is for for is not for non-radiographic axSpA. is for but not for axSpA. to of RCTs published the literature search are likely to likely to for are not in but be considered for axSpA if is review. of and in of is available for but not non-radiographic axSpA. is to for psoriasis but of in psoriasis of axSpA trial data published the literature search the of with but is not for Evidence for the safety of in is is not for non-radiographic axSpA. has evidence of efficacy for psoriasis but is not as a group are likely to for to of was not to in a trial of has evidence of efficacy for psoriasis but is not as a group are likely to for to of and for the Axial Spondyloarthritis based on is in and in questions and are on a rating scale of was on the and for the Axial Spondyloarthritis based on is in and in questions and are on a rating scale of was on the the clinical identified in the guideline two have not in a recommendation to of any quality evidence and are included as research The safety of targeted therapies on comorbidities and risk has from and was evidence to for across drugs in the and across but risks in may not be directly to axSpA to in the of risk and was also evidence on the clinical effectiveness and safety of targeted including for EMMs as the index Two clinical trials of in have efficacy for but has outcomes. This guideline to clinical to quality of care for axSpA. It does not for individual case that may have on management does to against of The recommendations are to be and in the available evidence but not limited by of recommendations from existing and drug which to does not the use of recommendation to use and pain are based on and data in the of the are by evidence in of The overarching of treatment quality of life through prevention of structural goal for which has of should be to of and use of the to care a diagnosis can be and is with the for to specialist can be but is not in clinical should be within and with the with axSpA. recommendations on EMMs management with other which may not be This to for where is clinical the when drug tapering for is of with for the may be more for people with axSpA than when independently without The to management at the of the guideline for targeted therapies the of individuals with lived experience and are typically the first in the only treatment a when resources (e.g. are or is to their in axSpA The GWG this for where clinical The GWG members research recommendations then to the management of targeted therapies in clinical trials. for Evidence on the use of targeted for and of therapeutic tapering. Management of axSpA. of in assessing treatment use of safety of targeted therapies in axSpA Safety and efficacy of targeted therapies in axSpA with A tool is available the BSR website and in Supplementary Data available at Rheumatology online. The GWG with the BSR Supplementary is available at Rheumatology online. data are provided in Supplementary available at Rheumatology online. was by a National for Health and and in by and and the was by the was by the was by a The views expressed are of the authors and not of the National Health the or the of were by the BSR to the literature review. has for from from has from to from from in and a at a and from in a case at a by has from to to a to and from and for and from and has to BSR and from and is an of and the is for from which from an agreement between and in this guideline working group as an expert has from for and to for from and from and has from to BSR in 2023. has from to BSR in from to BSR from to and from to in from to and of has for and from and has and and other from and to from at the and from has from and to from and an at on and the were and has research from and or consultation from and has research from to to in for and in has from and from and for has and at has research from and to from and from and has from and has from for to from for and from for BSR from is of Rheumatology The remaining authors have declared conflicts of The National Axial Spondyloarthritis The Society of The of and The Rheumatology and Society each the Society for Rheumatology guideline for the treatment of spondyloarthritis with biologic and targeted synthetic which was developed in with the BSR Creating Guidelines Protocol using of Guidelines for and The guideline working group to and and the Guideline Steering Group for their and and for with the systematic literature review.

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