Therapy of axSpA
Goal of therapy Details of therapies Sequential therapy for axSpA Choice of b/tsDMARD Tapering of bDMARDs Special notes on comorbidities Goal of therapy The goal of therapy is to achieve remission (ASDAS <1.3), or at least low disease activity (ASDAS <2.1). Details of therapies Disease-modifying antirheumatic drugs (DMARDs) These agents are divided into three broad groups: conventional synt
Special notes on comorbidities
Goal of therapy
The goal of therapy is to achieve remission (ASDAS <1.3), or at least low disease activity (ASDAS <2.1).
Details of therapies
Disease-modifying antirheumatic drugs (DMARDs)
These agents are divided into three broad groups: conventional synthetic (cs) DMARDs, biologic (b) DMARDs and targeted synthetic (ts) DMARDs. The bDMARDs are either biologic original (bo) DMARDs or biosimilar (bs) DMARDs, and include:
- tumour necrosis factor inhibitors (TNFi): either receptor blockers (etanercept (original and biosimilar) or monoclonal antibodies (infliximab (original and biosimilar)); adalimumab (original and biosimilar) and golimumab
- IL-17 inhibitors (IL-17i) (secukinumab and ixekizumab).
The tsDMARDs include the Janus kinase (JAK) inhibitors tofacitinib and upadacitinib. Baricitinib, a JAK2 inhibitor, is not currently approved for axSpA therapy.
Glucocorticoids
Patients with axial involvement should not receive long-term systemic glucocorticoids (GCs). If required, local injections of GCs at sites of inflammation may be considered.[45] Of note, GC injections into the achilles or patella tendons is associated with a risk of tendon rupture.
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) are first-line therapy for axSpA, and the response is usually excellent. The toxicity of these drugs should not be underestimated, and all NSAIDs should be used with caution. Many axSpA patients have risk factors for NSAID-induced gastrointestinal tract events, including older age (>60 years), as well as co-prescription of aspirin. Hence, there should be a low threshold for co-prescribing a proton pump inhibitor for gastro protection, or for considering a cyclooxygenase-2 (COX-2) selective agent.[46] In addition, all NSAIDs, both non-selective agents and selective COX-2 inhibitors, confer an increased risk of thrombotic events, and should be used with caution in patients with cardiovascular (CV) risk factors, although the CV risk induced by NSAIDs in axSpA remains controversial. Other side-effects of NSAIDs, including hypertension, renal and liver dysfunction, should not be forgotten. Analgesics such as paracetamol or opioids might be considered if there is an incomplete response to NSAIDs, or NSAIDs are contraindicated.
Sequential therapy for axSpA
| Table 3. Stepwise algorithm for therapy in axial spondyloarthritis | ||
| Step | Therapy | Inadequate response within 3 months |
| First-line therapy | NSAID | Proceed to second-line therapy |
| Second-line therapy (if peripheral arthritis) | Sulfasalazine 2 - 3 g/daily | Proceed to third-line therapy |
| Third-line therapy | b/tsDMARD (TNFi/IL-17i/JAKi) | Proceed to fourth-line therapy |
| Fourth-line therapy | Alternative b/tsDMARD (TNFi/IL-17i/JAKi) | |
| Tapering | Consider tapering if sustained remission × 6 months | Restart b/tsDMARD if flares |
| NSAID = non-steroidal anti-inflammatory drug; b/tsDMARD = biologic/targeted synthetic disease-modifying antirheumatic drug; TNFi = tumour necrosis factor inhibitor; IL-17i = interleukin-17 inhibitor; JAKi = Janus kinase inhibitor. | ||
First-line therapy: NSAIDs
Patients with predominantly axial manifestations associated with pain and stiffness should be commenced on an NSAID as first-line therapy provided there are no contraindications. The maximum recommended/tolerated dose should be titrated to response, side-effect profile and patient risk factors. A 2 - 4-week trial is recommended. If the response is poor, an alternate NSAID should be prescribed. Whether NSAIDs can retard radiographic progression (growth of syndesmophytes in the spine) in axSpA patients is controversial.[47-50] For patients who respond well to NSAIDs, continuous treatment is advised with appropriate monitoring.
Second-line therapy (if peripheral arthritis): Conventional synthetic disease-modifying drugs
Patients with purely axial disease should not be treated with csDMARDs as there is no evidence to support their use in axial disease.[51,52]
Sulphasalazine may be considered for patients with peripheral arthritis.[53] While there is no evidence to support the use of methotrexate (MTX) or leflunomide in patients with peripheral manifestations, they may be used in exceptional situations where other pharmacological treatment options are not available.
For extra-articular manifestations of axSpA, including psoriasis, uveitis and inflammatory bowel disease, csDMARDs may be beneficial (see ‘Guidelines for the management of peripheral SpA’ for details).
Third- and fourth-line therapy: b/tsDMARD therapy
South African Rheumatism and Arthritis Association (SARAA) eligibility criteria for b/tsDMARD therapies for axSpA:
- A diagnosis of definite axSpA made by a rheumatologist according to ASAS criteria
- Objective evidence of inflammation:
- elevated C-reactive protein (CRP), or
- MRI evidence of active sacroiliitis, or
- ultrasound evidence of inflammation in the joint/enthesitis/ dactylitis.
- Sustained high disease activity for two visits at least 4 weeks apart defined by:
- ASDAS score of >2.1
- spinal pain visual analogue scale (1 - 10 cm) ≥4.
- Failure of standard treatment:
- at least two NSAIDs during a 4-week period
- if peripheral arthritis, failure of sulfasalazine.
- Refractory enthesitis, uveitis or other extra-articular manifestations.
Choice of b/tsDMARD
There are, to date, no validated biomarkers or head-to-head studies of b/tsDMARD in axSpA to guide choice of biological agent in axSpA. On a group level, there are no differences in the efficacy of various TNFi for axSpA itself, but there are differences on an individual patient level, which remain poorly understood.[54] The choice of b/tsDMARD therapy depends on which SpA domain is involved, extraarticular disease, patient preference, tuberculosis risk, comorbidities, route of administration and cost. Details are offered in the peripheral SpA guidelines.
If the patient has extra-articular manifestations of uveitis or IBD, then monocloncal TNFi is preferred, and the soluble receptor (etanercept) should be avoided. Similarly, IL-17i and JAKi have not been shown to be efficacious in uveitis. IL-17i should not be used in patients with active IBD.[55] IL 12/23 inhibitors are not effective for axSpA. Baricitinib, a JAK2 inhibitor, is not currently approved for axSpA therapy.
The use of combination b/tsDMARDs is not recommended. In SpA (axial or peripheral), there is little evidence that co-prescription of MTX with b/tsDMARDs is necessary. All b/tsDMARDs should be initiated by a rheumatologist.
All patients with a rheumatic disease on b/tsDMARDs must be included, with patient consent, in the SARAA biologics registry (https:// www.saraa.co.za). Before commencing b/tsDMARD, appropriate screening and treatment for latent tuberculosis, hepatitis B, hepatitis C and HIV, in addition to vaccination, should be done.
The patient should be evaluated at 3 months to assess the response to treatment. If there is an improvement of the ASDAS ≥1.1 and/ or BASDAI ≥2, treatment should be continued. In the case of inadequate response to therapy, the patient needs review in terms of diagnosis of axSpA, structural damage v. active disease-causing symptoms (consider CRP and/or MRI scan) and adherence to therapy.
Tapering of bDMARDs
If the patient has a good response to therapy with sustained remission for a period of 6 months (ASDAS <1.3 and normal CRP on three consecutive visits or for 6 months), tapering of the bDMARDs might be considered in a shared decision-making process.[56,57] Tapering should either be in the form of reduction of dose or increasing the interval of administration. Tapering should be done slowly and cautiously to prevent any flares in disease. Discontinuation is not advised, as the evidence shows that a high proportion of patients experience disease flares.[58]
Special notes on comorbidities
Osteoporosis and spinal fracture
Screening for osteoporosis is recommended as per local protocol, remembering that sclerosis of the axial skeleton may make dual X-ray absorptiometry (DEXA) scan interpretation difficult – therefore DEXA of the wrist and hip (if unaffected by ankylosis) is recommended. Alternatively, dual-energy quantitative computed tomography may be used to assess the patient. Recently, the trabecular bone score mapping of L1-L4 derived from the DEXA image has been shown to be related to bone micro-architecture and fracture risk.[59]
If any significant changes in the patient’s pain/backache occur and the nature of the pain changes from inflammatory to mechanical, spinal fractures should be considered, and appropriate imaging and treatment are advised.[60] Risk factors for spinal fracture in axSpA include advanced age, higher BASFI, longer disease duration, low bone mineral density and osteoporosis.
Maharaj, A. B., et al. (2024). South African Rheumatism and Arthritis Association 2024 guidelines for the management of axial spondyloarthritis. South African Medical Journal, 114(10), e2668.