2025 BSR Guideline: Biologic‑ and Targeted‑Synthetic DMARDs for Axial Spondyloarthritis (axSpA)

Rheumatology (Oxford), 2025；DOI: 10.1093/rheumatology/keaf089 British Society for Rheumatology (BSR)；multidisciplinary expert task‑force; rheumatologists, physiotherapists, patient‑representatives, pharmacy‑specialists；evidence‑level grading 1A‑2B; statement‑agreement ≥ 95 % for core‑recommendationsPMC

Abstract

Objective This 2025 BSR guideline updates standards‑of‑care for biologic‑DMARD (bDMARD) and targeted‑synthetic DMARD (tsDMARD) therapy for radiographic‑axSpA (r‑axSpA) and non‑radiographic‑axSpA (nr‑axSpA). It addresses treatment‑initiation criteria, drug‑class‑selection guided by extra‑musculoskeletal‑manifestations (EMMs), monitoring, tapering‑versus‑withdrawal‑strategy, safety‑assessment, special‑populations and shared‑decision‑making with patientsuat.bsg.or....

Methods Systematic‑literature‑review of RCTs, observational‑real‑world‑cohorts and prior‑guidance up‑December 2024. Modified‑Delphi‑voting. Diagnosis must‑be‑confirmed by consultant‑rheumatologist before targeted‑therapy initiation. Non‑pharmacological‑care remains foundational alongside drug‑therapyPMC.

Conclusion TNF‑inhibitors, IL‑17‑inhibitors and selected‑JAK‑inhibitors are all valid‑first‑line‑targeted‑options for active‑axSpA after adequate‑conventional‑management. Drug‑class‑choice is driven largely‑by extra‑musculoskeletal‑comorbidities (uveitis, IBD, psoriasis). Tapering may‑be‑considered in sustained‑low‑disease‑activity; complete‑drug‑withdrawal is not‑routinely‑recommended. Multidisciplinary‑care‑model and patient‑centred‑shared‑decision‑making are mandatoryMedscape R....

Keywords: axial‑spondyloarthritis; axSpA; spondyloarthritis; bDMARD; tsDMARD; TNF‑inhibitor; IL‑17‑inhibitor; JAK‑inhibitor; BSR‑guideline

Overarching‑principles

1. Person‑centred‑care: treatment‑goals are co‑defined together‑with‑patients; quality‑of‑life, pain‑control, physical‑function and work‑participation are core‑outcomes alongside‑laboratory‑and‑imaging‑end‑pointsMedscape R....
2. Non‑pharmacological‑interventions (physiotherapy, supervised‑exercise, self‑management‑education, psychological‑support) must‑continue‑throughout‑targeted‑drug‑treatment and are‑never‑discontinued‑when‑starting b/tsDMARDsMedscape R....
3. Diagnosis of axSpA must‑be‑validated by consultant‑rheumatologist; avoid‑over‑diagnosis while‑reducing‑diagnostic‑delay.
4. Validated‑disease‑activity‑metrics should‑be‑documented at‑baseline and‑at‑every‑follow‑up‑visit. ASDAS is preferred‑over‑BASDAI for‑assessing‑inflammatory‑axial‑disease‑activity; BASDAI may‑be‑used as‑complementary‑toolPMC.
5. Choice‑among TNF‑i / IL‑17‑i / JAK‑i depends‑mainly‑on extra‑musculoskeletal‑manifestations, comorbid‑disease, safety‑profile, route‑of‑administration and‑patient‑preference, since‑no‑class‑shows‑overall‑superior‑efficacy‑for‑axial‑skeletal‑symptoms aloneuat.bsg.or....

1. Eligibility for biologic / targeted‑synthetic DMARD therapy

Initiation‑criteria (all‑required)

1. Confirmed‑diagnosis of axSpA (r‑axSpA or nr‑axSpA)
2. Persistent‑active‑inflammatory‑disease: elevated‑ASDAS, spinal‑pain, morning‑stiffness ≥ 30 min, objective‑inflammatory‑signs (elevated‑CRP and/or active‑sacroiliitis‑on‑MRI‑SI‑joints, especially‑for nr‑axSpA)
3. Inadequate‑response, intolerance or contra‑indication to adequate‑conventional‑pharmacological‑therapy (≥2‑different‑NSAIDs at‑max‑tolerated‑dose)
4. Shared‑decision‑making completed, risks‑and‑benefits‑discussed with‑patientPMC

Statement: TNF‑inhibitors, IL‑17‑inhibitors and‑licenced‑JAK‑inhibitors (tofacitinib, upadacitinib) are‑recommended‑treatment‑options for‑eligible‑active‑axSpA‑patients (1A‑evidence). Note: infliximab and‑tofacitinib are‑not‑licenced‑for‑nr‑axSpA within‑UK‑regulatory‑frameworkuat.bsg.or....

2. Drug‑class‑selection guided‑by‑extra‑musculoskeletal‑manifestations (EMMs)

2.1 Uveitis

• TNF‑inhibitors (especially‑monoclonal‑anti‑TNF‑antibodies: adalimumab, infliximab, golimumab, certolizumab‑pegol) are‑preferred‑for‑history‑of‑recurrent‑acute‑anterior‑uveitis.
• Etanercept shows‑weaker‑performance‑for‑uveitis‑prophylaxis.
• IL‑17‑inhibitors may‑be‑used with‑joint‑ophthalmology‑co‑monitoring;‑not‑first‑choice‑for‑recurrent‑uveitis‑patientsuat.bsg.or....

2.2 Inflammatory‑bowel‑disease (Crohn’s / ulcerative‑colitis)

• Monoclonal‑TNF‑inhibitors (infliximab, adalimumab, golimumab, certolizumab‑pegol): preferred‑if‑active‑or‑history‑of‑IBD.
• IL‑17‑inhibitors are‑generally‑avoided‑in‑active‑IBD‑due‑risk‑of‑intestinal‑flare‑exacerbation.
• Upadacitinib has‑demonstrated‑efficacy‑for‑both‑axSpA and‑IBD and‑is‑a‑valid‑alternative‑option for‑comorbid‑axSpA + IBDuat.bsg.or....

2.3 Psoriasis

• IL‑17‑inhibitors (secukinumab, ixekizumab, bimekizumab) are‑preferred‑for‑patients‑with‑moderate‑severe‑psoriasis‑skin‑involvement.
• TNF‑inhibitors are‑also‑effective‑for‑psoriasis‑comorbidityuat.bsg.or....

3. Monitoring strategy

1. Baseline‑pre‑treatment‑assessment:
   • Clinical: pain, stiffness, peripheral‑enthesitis‑/‑joint‑swelling, extra‑articular‑organ‑review (eyes, gut, skin)
   • Laboratory: CRP, full‑blood‑count, renal‑and‑liver‑function
   • Disease‑activity‑scores: ASDAS, BASDAI, patient‑global‑assessment
2. Early‑response‑assessment: evaluate‑treatment‑efficacy and‑tolerability 3‑4 months after‑starting‑targeted‑therapy
3. Stable‑phase‑follow‑up: reassess‑disease‑activity, safety‑and‑adherence every 6‑12 months; annual‑multidisciplinary‑review‑including‑cardiovascular‑and‑fracture‑risk‑screening is‑recommendedMedscape R....

If‑no‑clinically‑meaningful‑improvement by 3‑4 months: consider‑switch‑to‑another‑drug‑class‑of‑targeted‑therapy, after‑confirming‑good‑medication‑adherence and‑excluding‑non‑inflammatory‑causes‑of‑pain (e.g. degenerative‑spinal‑disease, fibromyalgia‑overlap)PMC.

4. Tapering, dose‑reduction and withdrawal

1. In‑patients‑achieving‑sustained‑low‑disease‑activity / remission: gradual‑dose‑tapering‑may‑be‑trialled under‑close‑monitoring.
2. Routine‑complete‑withdrawal of‑b/tsDMARD‑therapy is‑not‑recommended, as‑high‑flare‑risk‑exists‑after‑full‑stopping.
3. If‑flare‑occurs‑during‑tapering: escalate‑back‑to‑full‑licensed‑dose‑promptly.
4. Drug‑switch‑sequence: failure‑of‑one‑TNF‑inhibitor → may‑switch‑to‑another‑TNF‑agent,‑or‑to‑IL‑17‑inhibitor,‑or‑to‑JAK‑inhibitor,‑guided‑by‑EMMs‑and‑comorbiditiesMedscape R....

5. Special‑populations

5.1 Adolescents and young‑adults

• Paediatric‑licenced‑bDMARD‑options should‑be‑used where‑available; structured‑transition‑programme from‑paediatric‑to‑adult‑rheumatology‑service is‑mandatory.

5.2 Pregnancy‑and‑lactation

• Pre‑conception‑counselling is‑standard‑of‑care.
• Certolizumab‑pegol‑has‑minimal‑placental‑transfer and‑is‑preferred‑TNF‑agent‑if‑targeted‑therapy‑must‑continue‑through‑pregnancy‑for‑severe‑active‑axSpA.
• JAK‑inhibitors should‑be‑discontinued‑prior‑to‑planned‑conception‑due‑limited‑human‑pregnancy‑dataMedscape R....

5.3 Comorbid‑cardiovascular‑risk

• JAK‑inhibitor‑prescription‑requires‑pre‑treatment‑cardiovascular‑risk‑stratification; avoid‑or‑use‑with‑great‑caution‑in‑patients‑with‑history‑of‑MACE‑or‑high‑thromboembolic‑risk‑profileMedscape R....

6. Major‑new‑highlights compared‑with‑prior‑BSR‑guidance

1. Formal‑equal‑first‑line‑position for‑three‑major‑classes: TNF‑i,‑IL‑17‑i,‑licenced‑JAK‑i for‑both‑r‑axSpA and‑nr‑axSpA (with‑licence‑restriction‑noted for‑nr‑axSpA)uat.bsg.or....
2. Emphasis‑on‑ASDAS‑as‑primary‑inflammatory‑activity‑measure, moving‑beyond‑BASDAI‑alonePMC.
3. Detailed‑drug‑selection‑matrix‑based‑on‑uveitis,‑IBD‑and‑psoriasis‑extra‑musculoskeletal‑manifestationsuat.bsg.or....
4. Clear‑tapering‑versus‑withdrawal‑position: tapering‑allowed‑in‑low‑activity‑but‑routine‑full‑withdrawal‑discouraged‑due‑high‑flare‑riskMedscape R....
5. Strengthened‑mandate‑for‑non‑pharmacological‑therapy‑never‑to‑be‑abandoned‑when‑starting‑biologic‑or‑targeted‑oral‑drugsMedscape R....