Ankylosing Spondylitis Treatment Guidelines

Introduction to AS Management

• The American College of Rheumatology recommends that conventional synthetic DMARDs, such as sulfasalazine, methotrexate, and leflunomide, should not be used for axial disease in ankylosing spondylitis due to lack of proven efficacy 1, 2.

First-Line Treatment

• The European League Against Rheumatism suggests that NSAIDs are the mandatory first-line pharmacological treatment for AS patients with pain and stiffness, with continuous treatment preferred over on-demand dosing for patients with persistently active symptomatic disease 1, 2, 3, 4.
• The American College of Rheumatology recommends that biologic DMARDs, such as TNF inhibitors and IL-17 inhibitors, should be considered only after NSAIDs fail or are contraindicated 3, 5.

Biologic DMARDs

• The American College of Rheumatology strongly recommends TNF inhibitors as the biologic DMARD of choice for patients with persistently high disease activity despite NSAIDs, with approved options including adalimumab, etanercept, infliximab, golimumab, and certolizumab pegol 1, 2, 3, 5.
• The European League Against Rheumatism suggests that IL-17 inhibitors, such as secukinumab and ixekizumab, are equally valid first-line biologic options alongside TNF inhibitors, with no distinction in prioritization between the two 3, 5.
• The 2023 PANLAR guidelines recommend reserving JAK inhibitors, such as tofacitinib and upadacitinib, for situations where TNF inhibitors and IL-17 inhibitors are contraindicated or unavailable, due to increased cardiovascular and malignancy risks observed in rheumatoid arthritis populations 5.

Conventional Synthetic DMARDs

• The American College of Rheumatology states that there is no evidence supporting the use of conventional synthetic DMARDs, including sulfasalazine and methotrexate, for treating axial manifestations of AS, and that they should not be used for this indication 1, 2, 4.
• The European League Against Rheumatism suggests that sulfasalazine may be considered only in AS patients with active peripheral arthritis, not for axial symptoms, and that methotrexate has no proven benefit even for peripheral arthritis in AS 1, 2, 5, 4.

Treatment Algorithm

• The American College of Rheumatology recommends starting with continuous NSAIDs for pain and stiffness, and initiating biologic DMARD if persistently high disease activity despite NSAIDs, with a choice of TNF inhibitor or IL-17 inhibitor as first-line biologic 2, 3, 5.

Common Pitfalls to Avoid

• The European League Against Rheumatism advises against prescribing methotrexate or sulfasalazine for axial symptoms, requiring a trial of conventional DMARDs before biologics, adding methotrexate to TNF inhibitors in AS, and discontinuing biologics in stable patients, as these practices are not evidence-based and may lead to delayed or ineffective treatment 1, 3, 4, 6.

EULAR Recommendations for the Management of Axial Spondyloarthritis

First‑Line Pharmacologic Therapy

• NSAIDs at the maximum tolerated dose are the mandatory first‑line drug for all patients with axial spondyloarthritis. They should be used continuously in patients with persistent symptoms. 7
• If high disease activity persists despite (or the patient cannot tolerate) at least two NSAIDs, escalation to a biologic DMARD (TNF‑ inhibitor or IL‑17 inhibitor) is recommended. 8

Non‑Pharmacologic Management

• Regular supervised exercise and physiotherapy should start at diagnosis; supervised programs are superior to unsupervised home‑based regimens. 7
• In patients at high gastrointestinal risk, prescribe non‑selective NSAIDs together with gastro‑protective agents or use selective COX‑2 inhibitors. 9

Initiation of Biologic DMARDs (bDMARDs)

• Criteria to start a bDMARD: persistent high disease activity despite (or intolerance/contraindication to) ≥ 2 NSAIDs and at least one of the following:
  
  • Elevated C‑reactive protein (CRP)
  • Definitive inflammatory lesions on MRI
  • Radiographic sacroiliitis.
    Evidence of radiographic sacroiliitis fulfills the criterion.* 8
• First‑line biologic choice:
  
  • TNF‑ inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab) are the standard initial biologic. 7
  • IL‑17 inhibitors (secukinumab, ixekizumab) are equally valid as first‑line biologics, with no required prioritisation over TNF‑ inhibitors. 8

Switching After First bDMARD Failure

• After failure of a TNF‑ inhibitor, either switch to another TNF‑ inhibitor or initiate an IL‑17 inhibitor. 7

Corticosteroid Use

• Systemic corticosteroids are not recommended for axial disease. 9
• Targeted intra‑articular or peri‑articular steroid injections may be used for isolated musculoskeletal inflammation. 9

Conventional Synthetic DMARDs

• Sulfasalazine and methotrexate have no efficacy for axial manifestations. 9
• Sulfasalazine may be considered only for active peripheral arthritis. 9
• Failure of conventional synthetic DMARDs is not required before initiating biologic therapy for axial disease. 9

Treatment De‑Escalation

• In patients who achieve sustained remission, gradual tapering of the bDMARD can be considered, but complete discontinuation is not advised. [7][8]

Surgical Interventions

• Total hip arthroplasty is indicated for patients with refractory pain or functional limitation and radiographic structural damage, irrespective of age. [7][9]
• Corrective spinal osteotomy may be beneficial in selected patients with severe deformity. [7][9]