Ankylosing Spondylitis

Clinical Snapshot

Ankylosing spondylitis (AS) is the radiographic subset of axial spondyloarthritis (axSpA) — a chronic, immune-mediated inflammatory disease centred on the sacroiliac joints and spine, strongly associated with HLA-B27, that produces inflammatory back pain and progressive stiffness. AS refers specifically to axSpA with definite sacroiliitis visible on a plain radiograph (see Assessment & Diagnosis); non-radiographic axSpA describes the same disease process before, or without ever developing, that radiographic change, and shares essentially the same clinical presentation, extra-articular manifestations, and treatment approach.^[1]

Left inadequately controlled, chronic inflammation at the spine's entheseal insertions can drive new bone formation (syndesmophytes) that bridges adjacent vertebrae over years, producing the classic fused "bamboo spine" and a fixed, stooped posture — a structural outcome that current treatment aims to prevent, not merely to control symptoms.^[2] AS is 1 disease within a broader family — the spondyloarthritis (SpA) spectrum — that also includes psoriatic arthritis, reactive arthritis, inflammatory-bowel-disease-associated arthritis, and undifferentiated peripheral SpA. These conditions share genetic risk, extra-articular manifestations (acute anterior uveitis, inflammatory bowel disease, psoriasis), and much of their treatment ladder, which is why axSpA/AS management is best understood as 1 point on that shared spectrum rather than in isolation.

Recognize the Condition

The hallmark presentation is chronic inflammatory back pain — insidious low back and buttock pain, often alternating sides (reflecting sacroiliitis), with morning stiffness lasting more than 30 minutes that improves with activity and worsens with rest, frequently severe enough to wake the patient in the second half of the night. Onset is typically insidious, before age 45, and most often in the late teens through early 30s (see Assessment & Diagnosis for the specific screening criteria and why 2 different age cutoffs are used for 2 different purposes).^[3] Enthesitis — inflammation where a tendon or ligament inserts into bone — is a distinguishing SpA-spectrum feature, most classically at the Achilles tendon and plantar fascia insertions, and also seen at the costochondral junctions, iliac crests, and greater trochanters. Peripheral arthritis, when present, is typically an asymmetric oligoarthritis favouring the lower limbs (hips, knees, ankles) — a different pattern from rheumatoid arthritis's symmetric small-joint polyarthritis. Dactylitis ("sausage digit," diffuse swelling of an entire finger or toe) can occur, though it is more characteristic of psoriatic arthritis. As axial disease advances over years, reduced spinal mobility and chest expansion progress toward a fixed, stooped ("question mark") posture with loss of lumbar lordosis and increased thoracic kyphosis in untreated or inadequately controlled disease.

Extra-articular manifestations by system

Ocular

Acute anterior uveitis — the most common extra-articular manifestation, affecting up to about a third of patients over their disease course; typically unilateral, recurrent, and alternates sides between episodes. A sudden red, painful eye with photophobia and blurred vision in a patient with AS is acute anterior uveitis until an ophthalmologist says otherwise (see Red Flags & Refer).

Gastrointestinal

Clinically overt Crohn disease or ulcerative colitis develops in a meaningful minority of patients, and subclinical gut inflammation is even more common on endoscopic study — new or persistent bowel symptoms deserve real investigation, not dismissal as a medication side effect.

Dermatologic

Psoriasis co-occurs across the SpA spectrum and, when present, is a specific driver of biologic class selection (see Choose Initial Treatment).

Cardiovascular

Aortic root inflammation (aortitis) can cause aortic regurgitation, and cardiac conduction system involvement can cause atrioventricular block — both recognized complications of longstanding disease. AS also carries an elevated background cardiovascular event risk independent of these specific structural complications.^[1]

Pulmonary

Reduced chest wall expansion from costovertebral joint involvement; rare apical pulmonary fibrosis in longstanding, severe disease.

Renal

IgA nephropathy and, historically, secondary (AA) amyloidosis from longstanding uncontrolled inflammation — amyloidosis is now rare with modern disease control.

Neurologic

Cauda equina syndrome is a rare but recognized complication of longstanding, severe disease — a genuine surgical/neurologic emergency (see Red Flags & Refer).

Skeletal

Osteoporosis and an elevated vertebral fracture risk are present even in relatively young patients, and are compounded once the spine becomes rigid and fused — a fused, osteoporotic spine fractures with minimal trauma and behaves mechanically like a long bone, with a real risk of instability and spinal cord injury (see Red Flags & Refer and Monitoring & Follow-Up).

Risk Factors

HLA-B27 positivity — the strongest genetic association; present in roughly 90% of White patients with AS (lower in some other ancestries), though most HLA-B27-positive people never develop AS.
Family history of AS, axSpA, or another spondyloarthritis-spectrum condition.
Male sex — historically a more pronounced predominance in radiographic AS specifically than in non-radiographic axSpA, which has a more balanced sex distribution.
Onset before age 45, most commonly in the late teens through early 30s; new-onset AS is uncommon after age 45.
Cigarette smoking — associated with greater radiographic (structural) progression, higher measured disease activity, and a reduced response to TNF inhibitor therapy.
A personal history of psoriasis, inflammatory bowel disease, or reactive arthritis — each increases the risk of also developing axial spondyloarthritis.

Red Flags & Refer

New inflammatory back pain suggestive of axSpA deserves timely rheumatology referral for diagnosis confirmation — delayed diagnosis is common in AS and remains a real driver of preventable structural damage.^[2]

Suspected cauda equina syndrome — saddle anesthesia, new bowel or bladder dysfunction, or bilateral leg weakness in a patient with longstanding AS — same-day emergency assessment.
New acute red, painful eye with photophobia and blurred vision — same-day ophthalmology assessment for acute anterior uveitis; do not wait for a scheduled rheumatology visit.
New back or neck pain after even minor trauma in a patient with a longstanding fused ("bamboo") spine — treat as a probable spinal fracture until imaging proves otherwise. A rigid, osteoporotic fused spine fractures with minimal force, behaves mechanically like a long bone, and carries a real risk of instability and spinal cord injury; avoid neck manipulation and arrange urgent imaging and spine assessment.
New exertional dyspnea, syncope, or a new diastolic murmur — assess for aortic regurgitation or a cardiac conduction abnormality, both recognized complications of longstanding disease.
New or persistent bowel symptoms (diarrhea, blood in stool, abdominal pain) — investigate for inflammatory bowel disease, with particular attention in a patient on or being considered for an IL-17 inhibitor, a class that can trigger or worsen IBD.
Serious infection in a patient on a bDMARD or JAK inhibitor — hold the therapy until the infection resolves; do not continue dosing through it.
Symptoms suggesting tuberculosis reactivation or hepatitis B/C reactivation in a patient on or starting a bDMARD or JAK inhibitor.
Progressive loss of spinal mobility or chest expansion despite treatment — reassess disease control and escalate therapy rather than accept silent structural progression (see Monitoring & Follow-Up).

Assessment & Diagnosis

Differentiating inflammatory from mechanical back pain

Correctly identifying inflammatory back pain is the single most useful screening step for axSpA in a patient with chronic back pain, and changes the entire diagnostic pathway.

Feature	Inflammatory back pain (axSpA)	Mechanical back pain
Onset	Insidious, before age 45	Often acute, any age; frequently a clear precipitating event
Effect of exercise	Improves with activity	Worsens with activity
Effect of rest	No improvement, or worsens	Improves with rest
Morning stiffness	Over 30 minutes	Under 30 minutes, or absent
Nocturnal pain	Wakes the patient, characteristically in the 2nd half of the night, improving on rising and moving	Uncommon, or present throughout the night without improvement on movement
NSAID response	Often a rapid, marked improvement within 24-48 hours	Variable, usually partial
Buttock pain	Can alternate sides, reflecting sacroiliitis	Not typically alternating

The dedicated ASAS inflammatory-back-pain screening tool formalizes this: in a patient with chronic back pain, 4 or more of the following 5 parameters supports inflammatory back pain — onset before age 40, insidious onset, improvement with exercise, no improvement with rest, and pain at night with improvement on rising. Note that this specific screening tool uses an age-40 cutoff, distinct from the age-45 onset cutoff used as the entry criterion for the broader ASAS axSpA classification criteria below — 2 different tools built for 2 different purposes, not a contradiction. This tool performed comparably to older instruments (e.g., the Calin criteria) in validation studies and is a genuinely useful bedside screen, though it is a screening aid rather than a diagnostic test on its own — imaging and specialist assessment remain necessary to confirm axSpA.^[3]

History

Age at onset, pattern of onset, and response to exercise, rest, and NSAIDs (see the tables above).
Peripheral joint symptoms, enthesitis symptoms (heel pain, plantar fascia pain), and dactylitis.
Extra-articular symptom screen: eye redness or pain, bowel symptoms, psoriasis, and family history of any SpA-spectrum condition.

Physical examination

Modified Schober test — mark the skin at the lumbosacral junction (the dimples of Venus) and 10 cm above; ask the patient to bend forward maximally; an increase of less than 5 cm suggests reduced lumbar spinal flexion.
Chest expansion — measured at the 4th intercostal space between maximal expiration and inspiration; less than about 2.5 cm is abnormal and supports axial involvement.
Occiput-to-wall and tragus-to-wall distance — assesses cervical spine and thoracic kyphosis involvement in more advanced disease; both should be close to 0 in a patient able to stand fully upright against a wall.
Peripheral joint exam for synovitis; entheseal palpation (Achilles insertion, plantar fascia, greater trochanter, costochondral junctions); screen for dactylitis and psoriatic skin/nail changes.

Investigations

HLA-B27 — supportive but neither necessary nor sufficient on its own; a negative result does not exclude axSpA, especially outside White populations.
CRP and/or ESR — elevated in only about 40-50% of patients with active axSpA even at diagnosis; a normal CRP/ESR does not exclude active disease, a genuinely important distinguishing point from more uniformly CRP-driven conditions such as rheumatoid arthritis.
Plain radiographs of the sacroiliac joints — the first-line imaging test; look for the radiographic sacroiliitis defined in the modified New York criteria below.
MRI of the sacroiliac joints — obtained when radiographs are normal or equivocal and clinical suspicion remains, to detect active inflammation (bone marrow edema) before radiographic change has developed (non-radiographic axSpA).
CBC, creatinine, and a liver panel — baseline organ-function assessment before starting NSAID or DMARD/biologic therapy.

Modified New York criteria (1984) — the original AS-specific classification

The original disease-defining framework for AS combines 1 radiographic criterion with at least 1 of 3 clinical criteria. It remains useful as a teaching anchor for what "definite AS" (as opposed to non-radiographic axSpA) means, though the newer ASAS axSpA classification criteria below are now used more broadly in practice and research.^[4]

Criterion	Definition
Radiographic	Sacroiliitis on plain radiograph: bilateral grade 2-4, or unilateral grade 3-4 (0 = normal, 4 = complete ankylosis)
Plus at least 1 of the following clinical criteria
Low back pain	Present for 3 months or longer, improved by exercise, not relieved by rest
Lumbar spine motion	Limited in both the sagittal and frontal planes
Chest expansion	Reduced relative to normal values corrected for age and sex

"Definite AS" requires the radiographic criterion plus at least 1 clinical criterion. This framework predates modern MRI-based early detection and, by design, misses non-radiographic axSpA — it remains a valid definition of established, radiographically evident disease rather than a tool for early diagnosis.^[4]

ASAS classification criteria for axial spondyloarthritis

Applies to a patient with 3 months or longer of back pain with onset before age 45. Either arm below is sufficient, and both require imaging or laboratory confirmation rather than a clinical impression alone. Presented here as reference teaching content, not an interactive calculator — applying it correctly requires a hands-on assessment plus imaging/laboratory interpretation.^[5]

Arm	Requirement
Imaging arm	Sacroiliitis on imaging (active inflammation on MRI highly suggestive of SpA-associated sacroiliitis, or definite radiographic sacroiliitis per the modified New York criteria above) plus 1 or more additional SpA feature
Clinical arm	HLA-B27 positive plus 2 or more additional SpA features

SpA features usable toward either arm: inflammatory back pain, arthritis, enthesitis (heel), uveitis, dactylitis, psoriasis, Crohn disease/ulcerative colitis, good response to NSAIDs, family history of SpA, HLA-B27, and elevated CRP.

A patient meeting the imaging arm's radiographic-sacroiliitis definition, plus at least 1 clinical criterion from the modified New York framework above, is specifically classified as AS (radiographic axSpA) rather than non-radiographic axSpA — a distinction that matters for some jurisdictions' funding criteria but not for the treatment approach in this chapter, which applies to both.^[5]

Treatment Targets

Control signs, symptoms, and inflammation — pain, stiffness, and fatigue.
Prevent structural damage: slow or halt radiographic progression and new bone formation (syndesmophyte development) at the spine.
Preserve spinal mobility, chest expansion, physical function, work capacity, and quality of life.
Identify and manage extra-articular manifestations (uveitis, inflammatory bowel disease, psoriasis) and comorbidities (cardiovascular risk, osteoporosis) alongside the joint disease, not as an afterthought.
Regular clinical monitoring with an objective composite disease-activity measure (ASDAS or BASDAI — see Monitoring & Follow-Up), adjusting therapy when disease remains active, is recommended.^[6] A dedicated treat-to-target strategy trial in axSpA did not show a formal treat-to-target protocol to be superior to good-quality usual care judged against the same measures — a genuine, honestly-reported difference from the stronger treat-to-target evidence base in rheumatoid arthritis — so regular, attentive monitoring and responsive treatment adjustment matter more than adherence to any single rigid protocol.^[2]

Choose Initial Treatment

Direct treatment rule

Confirmed active axSpA/AS, 1st line start an NSAID at the maximum tolerated/labelled dose, given continuously — not simply as needed — for at least 2-4 weeks before judging response; a clear symptomatic improvement within 24-48 hours of a therapeutic NSAID dose is itself a genuinely useful diagnostic clue supporting axSpA over a mechanical cause.^[2]

1st NSAID inadequately effective or not tolerated trial a 2nd, different NSAID at its own maximum tolerated dose before concluding NSAID therapy has failed — individual response varies meaningfully between agents, and this step should not be skipped.^[2]

Do not expect axial benefit from methotrexate or sulfasalazine — unlike in rheumatoid arthritis, conventional synthetic DMARDs have no proven efficacy for axial (spinal/sacroiliac) disease; sulfasalazine has modest evidence limited to the peripheral-arthritis component only, and is not a substitute for a biologic when axial disease is active.^[6]

Active disease despite an adequate trial of 2 or more NSAIDs at maximal tolerated dose, or NSAID intolerance/contraindication start a biologic — a TNF inhibitor or an IL-17 inhibitor, both strongly recommended and treated as therapeutically comparable 1st-line options rather than 1 being generally preferred over the other.^[2]

Recurrent acute anterior uveitis, or active/past inflammatory bowel disease prefer a TNF monoclonal antibody — adalimumab, infliximab, golimumab, or certolizumab pegol — over etanercept, which is a soluble receptor fusion protein and is meaningfully less effective for these 2 extra-articular manifestations specifically, and over an IL-17 inhibitor, which can trigger or worsen IBD.^[6]

Significant coexisting psoriasis, without active uveitis or IBD an IL-17 inhibitor (secukinumab or ixekizumab) is a reasonable preferred choice given added efficacy for skin disease.^[6]

Predominant peripheral arthritis without significant axial disease a local corticosteroid injection (sacroiliac joint or affected enthesis/peripheral joint) can help control a flare; sulfasalazine is a reasonable specific option for the peripheral-joint component only, before escalating to a biologic.

Do not rely on long-term systemic corticosteroids — unlike rheumatoid arthritis, there is little evidence supporting their use in axSpA, and AS patients already carry an elevated baseline fracture risk that systemic corticosteroids would only compound.^[6]

Do not choose a JAK inhibitor as the 1st non-NSAID therapy — upadacitinib and tofacitinib are reserved in Canada for inadequate response to, or intolerance of, a bDMARD, given the class-wide cardiovascular/malignancy/thrombosis safety signal.^[2]

Before starting any bDMARD or JAK inhibitor complete tuberculosis and hepatitis B/C screening and confirm immunizations are current (see Monitoring & Follow-Up) — do not start immunosuppression before this is done.

Non-Pharmacologic Treatment

Structured exercise is an essential, first-line component of AS treatment — not an optional adjunct — and should be prescribed at diagnosis regardless of current disease activity or drug therapy.^[6] Effective programs combine stretching/flexibility work, strengthening, and aerobic conditioning; supervised, individual, or group-based (including patient-association exercise groups) formats all have evidence of benefit for pain, spinal mobility, and function.
Encourage extension-based exercises and attention to posture specifically to counter the disease's natural tendency toward a flexed, stooped spine as it progresses — a genuinely disease-specific rationale beyond general fitness advice.
Both land-based and water-based (aquatic) exercise programs have supporting evidence; swimming is commonly recommended given its low-impact, extension-promoting nature.
Physiotherapy referral at diagnosis, with periodic reassessment and program adjustment as disease activity and mobility change over time.
Smoking cessation — reduces radiographic progression risk and improves response to TNF inhibitor therapy, in addition to general cardiovascular benefit.
Patient education and self-management programs, including connection with patient associations (e.g., the Canadian Spondylitis Association), improve long-term engagement with the exercise-centred treatment plan.
Occupational/ergonomic counselling — workstation and sleep-posture adjustments to minimize sustained spinal flexion.
There is no good evidence to support a specific diet or complementary/alternative therapy for disease control.

Pharmacologic Treatment Options

Drug / intervention	Role	Dose / use	Important adverse effects	Teaching points
Naproxen Preferred	1st-line NSAID, given continuously	500 mg PO twice daily, up to 1000 mg/day	GI upset, GI ulceration/bleeding, cardiovascular risk	Give continuously, not PRN, for a genuine treatment trial; try a 2nd NSAID before concluding NSAID therapy has failed.
Indomethacin Preferred	1st-line NSAID; historically among the most effective agents specifically in AS	25-50 mg PO three times daily, or 75 mg extended-release once-twice daily, up to 150-200 mg/day	GI upset, GI ulceration/bleeding, headache, dizziness	CNS adverse effects are more prominent with this agent than with other NSAIDs; take with food.
Celecoxib Alternative	Preferred when GI bleeding risk is elevated	200 mg PO once or twice daily, up to 400 mg/day	Lower GI risk than nonselective NSAIDs; cardiovascular risk	COX-2 selective; confirm cardiovascular risk profile before long-term continuous use, as with any NSAID.
Meloxicam Alternative	Alternative continuous NSAID	15 mg PO once daily	GI upset, GI ulceration/bleeding, cardiovascular risk	Once-daily dosing may help adherence with continuous therapy.
Sulfasalazine Special situation	Peripheral arthritis component only — no proven axial benefit	Initial 500 mg PO daily-twice daily, increase by 500 mg weekly to 2-3 g/day PO in 2 divided doses	Rash, GI intolerance, bone marrow suppression	Do not use in place of a biologic for active axial disease; a reasonable option specifically for peripheral joint involvement.
Adalimumab Preferred	1st-line bDMARD (TNF monoclonal antibody)	40 mg SC every 2 weeks	Injection-site reaction, serious infection	Preferred over etanercept when uveitis or inflammatory bowel disease is present.
Etanercept Alternative	1st-line bDMARD option without significant uveitis/IBD	50 mg SC once weekly	Injection-site reaction, serious infection	Less effective for uveitis and IBD than a TNF monoclonal antibody — avoid preferring it when either is present.
Infliximab Special situation	TNF monoclonal antibody bDMARD	5 mg/kg IV at weeks 0, 2, and 6, then every 6-8 weeks	Infusion reactions, serious infection	Higher approved AS starting dose than the equivalent rheumatoid arthritis regimen; given only IV.
Golimumab Alternative	TNF monoclonal antibody bDMARD	50 mg SC once monthly	Injection-site reaction, serious infection	Once-monthly dosing on the same date each month.
Certolizumab pegol Alternative	TNF monoclonal antibody bDMARD; pregnancy-compatible	400 mg SC at weeks 0, 2, and 4, then 200 mg SC every 2 weeks or 400 mg SC every 4 weeks	Injection-site reaction, serious infection	The pegylated antibody fragment does not cross the placenta — preferred TNF inhibitor when a biologic is needed close to delivery.
Secukinumab Alternative	IL-17 inhibitor bDMARD	150 mg SC at weeks 0, 1, 2, and 3, then 150 mg SC every 4 weeks (300 mg option for inadequate response)	Nasopharyngitis, mucocutaneous candidiasis	Avoid, or use with caution, in active or strongly suspected inflammatory bowel disease — this class can trigger or worsen IBD.
Ixekizumab Alternative	IL-17 inhibitor bDMARD	160 mg SC (two 80 mg injections) at week 0, then 80 mg SC every 4 weeks	Nasopharyngitis, mucocutaneous candidiasis	Same inflammatory bowel disease caution as secukinumab.
Upadacitinib Special situation	JAK inhibitor (tsDMARD), after bDMARD failure only	15 mg PO once daily	Serious infection, malignancy, MACE, thrombosis — boxed warning, all class members	Reserve for inadequate response to, or intolerance of, a bDMARD; added caution in patients 65+, smokers, or with cardiovascular/malignancy risk factors.
Tofacitinib Special situation	JAK inhibitor (tsDMARD), after bDMARD failure only	5 mg PO twice daily	Serious infection, malignancy, MACE, thrombosis — boxed warning, all class members	Same positioning and precautions as upadacitinib.

Special Populations

Pregnancy: unlike rheumatoid arthritis, AS does not reliably improve during pregnancy — disease activity can remain unchanged or worsen, and postpartum flares are common, so most patients continue needing active management through pregnancy.^[1] Discuss family planning and confirm a pregnancy-compatible regimen before a planned pregnancy in every patient of reproductive age.

NSAIDs can be used in the 1st and 2nd trimesters but should be avoided in the 3rd trimester given antiprostaglandin effects (premature ductus arteriosus closure, oligohydramnios, and interference with labour).
Sulfasalazine can be continued throughout pregnancy with folic acid supplementation, given sulfasalazine's antifolate effect.
Certolizumab pegol is compatible with all trimesters given minimal-to-no placental transfer, and is generally the preferred TNF inhibitor when a biologic is needed close to delivery.
Adalimumab, etanercept, golimumab, and infliximab can generally be continued through the 2nd trimester, with increasing placental transfer in the 3rd trimester — discuss infant live-vaccine timing with the treating team whenever 1 of these was used later in pregnancy.
IL-17 inhibitors and JAK inhibitors have limited human pregnancy data — avoid unless no adequate alternative controls disease.
Methotrexate is not used for AS, so its pregnancy contraindication is not a practical issue in this chapter, unlike in rheumatoid arthritis.

Breastfeeding

NSAIDs (short-acting agents preferred), sulfasalazine (except in an infant with hyperbilirubinemia), and certolizumab pegol are compatible with breastfeeding. Data for other bDMARDs and for JAK/IL-17 inhibitors in lactation are limited; biologics generally transfer into breast milk only in small amounts given their large molecular size, and use is decided case-by-case with the treating specialist.

Pediatric

Enthesitis-related arthritis is the pediatric SpA-spectrum category and is a distinct clinical entity with its own specialist-directed approach — this chapter covers adult AS/axSpA only. A patient with childhood-onset axial or enthesitis-predominant inflammatory disease needs pediatric rheumatology referral rather than adult-dosing extrapolation.

Perioperative and anesthesia considerations

Advanced AS with cervical spine involvement and reduced neck extension is a genuine difficult-airway/intubation risk that must be flagged before any procedure requiring general anesthesia — distinct in mechanism from rheumatoid arthritis's atlantoaxial subluxation risk, but requiring the same proactive anesthesia-team notification. Hold a bDMARD before elective surgery, timing withdrawal to the end of that agent's dosing cycle, and restart once the wound shows evidence of healing; hold a JAK inhibitor for at least 7 days before surgery. NSAIDs and sulfasalazine can typically continue through minor surgery; confirm the specific plan with the treating rheumatologist.

Renal and hepatic impairment

NSAIDs require particular caution with chronic continuous use given the AS treatment approach itself — periodically reconfirm renal function, especially in an older patient or one with additional cardiovascular/renal risk factors, and do not assume long-term continuous NSAID therapy is risk-free simply because it is guideline-recommended. Most bDMARD/tsDMARD dosing is not renally or hepatically adjusted, but active infection and organ function should be reconfirmed before every dose escalation.

Older adults

New-onset AS is uncommon after age 45, but a patient can carry years of unrecognized symptoms before diagnosis at an older age. Apply the JAK-inhibitor cardiovascular/malignancy risk stratification specifically at age 65 and older, favouring a bDMARD first unless TNF-inhibitor therapy has already failed or was not tolerated, and reassess the ongoing necessity and renal/GI/cardiovascular safety of continuous NSAID therapy more frequently in this group.

Monitoring & Follow-Up

See patients with active disease every 3-6 months; extend the interval once disease is well-controlled. Adjust therapy against persistent active disease rather than continuing an unchanged regimen — see Treatment Targets for the evidence nuance around formal treat-to-target protocols in axSpA specifically.^[2]

Disease activity measurement (ASDAS and BASDAI)

The Ankylosing Spondylitis Disease Activity Score (ASDAS) — a weighted composite of patient-reported back pain, peripheral pain/swelling, duration of morning stiffness, patient global assessment, and CRP or ESR — is the current preferred composite measure; the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a fully patient-reported 0-10 index across 6 symptom domains, remains widely used, particularly where CRP testing is less accessible. Both use continuously weighted formulas and structured longitudinal tracking best done by the specialist team, and are presented here as reference only, with no self-service calculator.

ASDAS category	Score
Inactive disease	Under 1.3
Low disease activity	1.3 to under 2.1
High disease activity	2.1 to 3.5
Very high disease activity	Over 3.5

Spinal mobility and function

Reassess the modified Schober test, chest expansion, and occiput/tragus-to-wall distance (see Assessment & Diagnosis) at least annually, even when symptoms are well-controlled — structural progression can be clinically silent, and a falling mobility measure is itself a reason to reassess disease control rather than assume treatment is working.

Pre-biologic screening

Tuberculosis: chest x-ray and a TST or IGRA before starting any bDMARD or JAK inhibitor; exclude active TB and start isoniazid prophylaxis in anyone who screens positive before proceeding.
Hepatitis B and C serology before starting any bDMARD or JAK inhibitor.

Vaccination around immunosuppression

Update vaccinations before starting therapy whenever possible, particularly for any live vaccine. Live vaccines are avoided during bDMARD or JAK-inhibitor therapy; inactivated/recombinant vaccines remain recommended once therapy has started. Use the recombinant (inactivated) herpes zoster vaccine, never the live formulation, in a patient on or starting immunosuppression.

Ocular surveillance

There is no routine surveillance eye-exam schedule for AS, unlike hydroxychloroquine retinopathy monitoring in some other conditions — the actual, effective screening strategy is patient education: every patient should know to seek same-day ophthalmology assessment for any new red, painful eye with photophobia, given the substantial lifetime anterior uveitis risk (see Red Flags & Refer).

Bone health

Consider DXA screening given the elevated fracture risk in AS, particularly with longstanding or advanced (fused) disease; ensure adequate calcium (about 1200 mg/day total intake) and vitamin D (800-2000 units/day), and add a bisphosphonate when osteoporosis is confirmed or fracture risk is significant.

Cardiovascular risk

Routine cardiac screening (e.g., ECG or echocardiography) is not recommended in an asymptomatic patient with AS and no cardiac symptoms — reserve cardiac workup for the red-flag presentations above.^[2] Do apply standard age-appropriate cardiovascular risk-factor management (blood pressure, lipids, glucose, smoking cessation) given AS's elevated background cardiovascular risk independent of any specific cardiac complication.^[1]

Renal and GI monitoring for chronic NSAID therapy

Periodic creatinine and CBC given that long-term continuous NSAID use is the treatment approach itself in axSpA, not an occasional add-on; reassess GI bleeding risk and consider gastroprotection for a patient with additional risk factors.

Treatment Failure / Next Step

Confirm an adequate NSAID trial before declaring failure — maximum tolerated/labelled dose, given continuously (not PRN), for at least 2-4 weeks, with at least 2 different NSAIDs tried.
Confirm adherence — continuous, not intermittent, dosing is a common, reversible cause of apparent nonresponse.
Reassess disease activity with a structured measure (ASDAS or BASDAI), not symptoms alone, before escalating.
If active disease persists despite adequate NSAID trials, start a biologic — a TNF monoclonal antibody for recurrent uveitis or active/past IBD, an IL-17 inhibitor for significant psoriasis without uveitis/IBD, or either class when no extra-articular manifestation predominates — after completing pre-biologic screening.
Give the 1st bDMARD an adequate trial, typically around 12 weeks, before judging inadequate response.
If inadequate response to the 1st bDMARD, switch to a 2nd bDMARD — either within the same class or to the other class — reconsidering extra-articular manifestations again when choosing.
If inadequate response to 2 bDMARDs (ideally 1 from each class), consider a JAK inhibitor (upadacitinib or tofacitinib), applying the cardiovascular/malignancy risk stratification first.
In a patient who has achieved sustained remission or inactive disease on a bDMARD, cautious dose tapering (reduced dose or extended interval), rather than abrupt discontinuation, can be considered — full discontinuation is associated with a high relapse rate.^[6]
Persistent, localized peripheral or entheseal symptoms despite good axial disease control can often be addressed with a local corticosteroid injection rather than escalating systemic therapy.
At any step, re-examine the original diagnosis if response remains genuinely inadequate despite confirmed adherence and adequate trials.

Common Errors to Avoid

Dosing an NSAID only as needed instead of continuously in active axSpA — undermines both symptom control and the guideline-supported treatment rationale.
Prescribing methotrexate, or relying on sulfasalazine, expecting axial (spinal) benefit — neither has proven efficacy for axial disease; sulfasalazine's evidence is limited to the peripheral-joint component.
Declaring NSAID failure after trialing only 1 agent — a 2nd, different NSAID deserves a genuine trial first.
Choosing etanercept over a TNF monoclonal antibody in a patient with active or recurrent anterior uveitis or inflammatory bowel disease — etanercept is meaningfully less effective for these manifestations.
Choosing an IL-17 inhibitor in a patient with active or strongly suspected inflammatory bowel disease — this class can trigger or worsen IBD.
Reaching for a JAK inhibitor as the 1st non-NSAID therapy instead of after bDMARD failure.
Skipping tuberculosis and hepatitis B/C screening before starting a bDMARD or JAK inhibitor.
Ordering routine cardiac screening in an asymptomatic AS patient with no cardiac symptoms — not supported; use standard risk-factor management instead, and reserve cardiac workup for genuine red-flag presentations.
Missing an acute uveitis presentation because the patient or clinician did not recognize the eye-spine connection — proactively educate every patient at diagnosis.
Manipulating the neck, or delaying imaging, after new pain in a patient with a longstanding fused spine — treat as a probable fracture until proven otherwise.
Treating structured exercise as optional or secondary to medication — it is an essential, first-line component of therapy in its own right.
Continuing chronic NSAID therapy indefinitely without periodic renal, GI, and cardiovascular risk reassessment.

Clinical Decision Algorithm

Recognizing inflammatory back pain and confirming the diagnosis

Chronic back pain lasting 3 months or longer, with onset before age 45

Screen for inflammatory back pain: insidious onset, improvement with exercise, no improvement with rest, night pain that improves on rising, and onset before age 40 (this screening tool's own cutoff) — 4 of 5 present supports inflammatory back pain^[3]

Features suggestive of inflammatory back pain

Order HLA-B27 and sacroiliac joint imaging (plain radiograph first; MRI if radiograph is normal/equivocal and suspicion remains) and refer to rheumatology

Apply the ASAS axSpA classification criteria (imaging arm or clinical arm) to confirm the diagnosis^[5]

Mechanical features predominate

Manage as mechanical back pain; reconsider axSpA if red-flag or SpA-spectrum features emerge later

Initial pharmacologic therapy: continuous NSAID trial

Confirmed axSpA/AS, active disease

Start an NSAID (naproxen, indomethacin, celecoxib, or meloxicam) at the maximum tolerated dose, given continuously — not PRN^[2]

Inadequate response after 2-4 weeks

Trial a 2nd, different NSAID at its own maximum tolerated dose before concluding NSAID therapy has failed

Good response

Continue continuous NSAID therapy; reassess periodically with ASDAS/BASDAI and consider dose reduction once disease is stable/inactive

Active disease persists despite 2 or more adequate NSAID trials, or NSAID intolerance/contraindication — proceed to biologic selection^[2]

Biologic selection and escalation

NSAID failure/intolerance; tuberculosis and hepatitis B/C screening complete, immunizations current

Recurrent anterior uveitis, or active/past IBD

Prefer a TNF monoclonal antibody — adalimumab, infliximab, golimumab, or certolizumab pegol (not etanercept, and not an IL-17 inhibitor)^[6]

Significant psoriasis, no uveitis/IBD

An IL-17 inhibitor — secukinumab or ixekizumab — is a reasonable preferred choice^[6]

No dominant extra-articular driver

A TNF inhibitor or an IL-17 inhibitor — either is a reasonable, therapeutically comparable 1st-line biologic^[2]

Inadequate response to the 1st bDMARD after an adequate trial (about 12 weeks) — switch to a 2nd bDMARD, within the same class or the other class, reconsidering extra-articular manifestations again

Inadequate response to 2 bDMARDs — consider a JAK inhibitor (upadacitinib or tofacitinib), applying the cardiovascular/malignancy risk stratification first^[2]

Drug Tables

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

NSAIDs — continuous therapy is the treatment approach itself in axSpA

Any of the agents below is a reasonable 1st choice; a 2nd, different NSAID deserves its own genuine trial before concluding NSAID therapy has failed.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Naproxen	Adults: 500 mg PO twice daily, up to 1000 mg/day	GI upset, GI ulceration/bleeding, cardiovascular risk	Increased bleeding with anticoagulants; reduces antihypertensive efficacy of ACE inhibitors/ARBs/diuretics	Give continuously, not PRN, for a genuine treatment trial.
Indomethacin	Immediate-release: 25-50 mg PO three times daily Extended-release: 75 mg PO once or twice daily, up to 150-200 mg/day	GI upset, GI ulceration/bleeding, headache, dizziness, cardiovascular risk	Increased bleeding with anticoagulants; reduces antihypertensive efficacy of ACE inhibitors/ARBs/diuretics; increased lithium levels	Historically among the most effective NSAIDs specifically in AS; CNS adverse effects are more prominent with this agent than with other NSAIDs — take with food.
Celecoxib	Adults: 200 mg PO once or twice daily, up to 400 mg/day	GI upset, lower GI ulceration/bleeding risk than nonselective NSAIDs, cardiovascular risk	Increased bleeding with anticoagulants; reduces antihypertensive efficacy of ACE inhibitors/ARBs/diuretics	COX-2 selective — preferred when GI bleeding risk is elevated; confirm cardiovascular risk profile before long-term continuous use.
Meloxicam	Adults: 15 mg PO once daily	GI upset, GI ulceration/bleeding, cardiovascular risk	Increased bleeding with anticoagulants; reduces antihypertensive efficacy of ACE inhibitors/ARBs/diuretics	Once-daily dosing may help adherence with continuous therapy.

Conventional synthetic DMARD — peripheral arthritis only

No proven efficacy for axial (spinal/sacroiliac) disease — not a substitute for a biologic when axial disease is active.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Sulfasalazine	Adults: Initial 500 mg PO daily or twice daily, increase by 500 mg weekly to a maintenance dose of 2-3 g/day PO in 2 divided doses	Rash, bone marrow suppression, GI intolerance, photosensitivity	May decrease GI absorption of digoxin	Reasonable specifically for the peripheral-joint component; avoid with sulfa allergy or G6PD deficiency; enteric-coated tablets reduce GI upset. May be used in pregnancy with folic acid supplementation.

Tumor necrosis factor (TNF) inhibitors

1st-line bDMARD class. A TNF monoclonal antibody (every agent in this class except etanercept) is preferred over etanercept, and over an IL-17 inhibitor, when recurrent anterior uveitis or inflammatory bowel disease is present. Complete TB and hepatitis B/C screening before starting every agent in this class.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Adalimumab	Adults: 40 mg SC every 2 weeks	Injection-site reactions; infections including TB and opportunistic organisms; rare lymphoma/other malignancy	None major beyond additive infection risk with other immunosuppressants	A TNF monoclonal antibody — preferred over etanercept when uveitis or inflammatory bowel disease is present.
Etanercept	Adults: 50 mg SC once weekly	Injection-site reactions; infections including TB and opportunistic organisms; may increase the risk of new-onset inflammatory bowel disease	None major beyond additive infection risk with other immunosuppressants	A receptor fusion protein, not a monoclonal antibody — meaningfully less effective for uveitis and IBD than the monoclonal-antibody TNF inhibitors; avoid preferring it when either is present.
Infliximab	Adults: 5 mg/kg IV at weeks 0, 2, and 6, then every 6-8 weeks	Infusion reactions; infections including TB and opportunistic organisms; rare lymphoma/other malignancy	None major beyond additive infection risk with other immunosuppressants	A chimeric mouse-human monoclonal antibody given only IV; the approved AS starting dose is higher than the equivalent rheumatoid arthritis regimen.
Golimumab	Adults: 50 mg SC once monthly	Injection-site reactions; infections including TB and opportunistic organisms	None major beyond additive infection risk with other immunosuppressants	Once-monthly dosing on the same date each month.
Certolizumab pegol	Loading: 400 mg SC at weeks 0, 2, and 4 Maintenance: 200 mg SC every 2 weeks, or 400 mg SC every 4 weeks	Injection-site reactions; infections including TB and opportunistic organisms	None major beyond additive infection risk with other immunosuppressants	The pegylated antibody fragment does not cross the placenta — preferred TNF inhibitor when a biologic is needed close to delivery.

Interleukin-17 (IL-17) inhibitors

Equivalent 1st-line biologic option to a TNF inhibitor; a reasonable preferred choice when significant psoriasis is present without uveitis or IBD. Avoid, or use with caution, in active or strongly suspected inflammatory bowel disease — this class can trigger or worsen IBD. Complete the same pre-therapy infection screening as the TNF inhibitors.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Secukinumab	Loading: 150 mg SC at weeks 0, 1, 2, and 3 Maintenance: 150 mg SC every 4 weeks, starting at week 4 (300 mg every 4 weeks for an inadequate response)	Nasopharyngitis, upper respiratory infection, mucocutaneous candidiasis; infection risk	None major beyond additive infection risk with other immunosuppressants
Ixekizumab	Loading: 160 mg SC (two 80 mg injections) at week 0 Maintenance: 80 mg SC every 4 weeks	Nasopharyngitis, upper respiratory infection, mucocutaneous candidiasis; infection risk	None major beyond additive infection risk with other immunosuppressants

Janus kinase (JAK) inhibitors (tsDMARDs)

Reserved for inadequate response to, or intolerance of, a bDMARD — currently the only 2 JAK inhibitors approved for axSpA in Canada. Both carry a class-wide boxed warning for serious infections, malignancy/lymphoma, major adverse cardiovascular events, and thrombosis; use with added caution — favouring a TNF inhibitor or IL-17 inhibitor first — in patients 65 or older, current or past smokers, or those with additional cardiovascular risk factors or a malignancy history.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Upadacitinib	Adults: 15 mg PO once daily	Infections (including TB, herpes zoster); increased lymphoma/malignancy risk; venous thromboembolism; increased lipids; neutropenia	Caution with potent CYP3A4 inhibitors/inducers	Screen for latent/active TB before starting; monitor lipids and CBC periodically.
Tofacitinib	Adults: 5 mg PO twice daily	Infections (including TB, herpes zoster); increased lymphoma/malignancy risk; venous thromboembolism; increased lipids; neutropenia	Reduce dose with potent CYP3A4 inhibitors	Screen for latent/active TB before starting; monitor lipids and CBC periodically.

Local corticosteroid injection

For a flare localized to a small number of peripheral joints, entheseal sites, or the sacroiliac joint itself; not a substitute for adequate systemic disease control.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Triamcinolone (intra-articular/entheseal/sacroiliac injection)	Injection: Dose individualized to the target site, per product labelling	Local tissue/skin atrophy at the injection site; transient post-injection flare	Increased GI ulceration risk with concurrent NSAID use	Image-guided injection is often used for sacroiliac joint injections given the joint's depth and anatomy.

Pre-biologic infection prophylaxis

Drug	Dosage	Adverse effects	Drug interactions	Comments
Isoniazid	Adults: Per current Canadian TB standards, individualized to the screening result and infectious disease/TB program guidance	Hepatotoxicity, peripheral neuropathy (reduced by co-administered pyridoxine)	Increased phenytoin levels; avoid excessive alcohol given additive hepatotoxicity	For latent TB confirmed by TB screening before starting a bDMARD or JAK inhibitor; give with pyridoxine to reduce neuropathy risk. Exclude active TB before starting.
Pyridoxine (vitamin B6)	Adults: 25-50 mg PO daily	Well tolerated at prophylactic doses	None significant	Co-administered with isoniazid to reduce peripheral neuropathy risk.
Tenofovir disoproxil fumarate	Adults: 300 mg PO once daily	Renal impairment, decreased bone mineral density	Avoid other nephrotoxic agents when possible; monitor renal function	Antiviral prophylaxis for a hepatitis-B-positive or previously-infected (anti-HBc-positive) patient starting a bDMARD or JAK inhibitor.
Entecavir	Adults: 0.5 mg PO once daily	Headache, fatigue; rare lactic acidosis	None major	Alternative antiviral prophylaxis agent for the same hepatitis B indication as tenofovir.

Bone-health support

For a patient with confirmed osteoporosis or significant fracture risk (see Monitoring & Follow-Up).

Drug	Dosage	Adverse effects	Drug interactions	Comments
Calcium carbonate	Adults: Individualized to reach a total elemental calcium intake of about 1200 mg/day	Constipation, GI upset	Reduces absorption of levothyroxine, tetracyclines, and some fluoroquinolones if co-administered — separate dosing by at least 2 hours	Aim for about 1200 mg/day total elemental calcium intake, preferably from diet with supplementation making up any gap.
Vitamin D3	Adults: 800-2000 units PO daily	Well tolerated at recommended doses; hypercalcemia with excessive doses	None significant at standard doses
Alendronic acid	Adults: 70 mg PO once weekly, taken with a full glass of water while remaining upright for at least 30 minutes	Esophageal irritation, GI upset; rare osteonecrosis of the jaw or atypical femur fracture with long-term use	Calcium, antacids, and other oral medications reduce absorption — take on an empty stomach, 30 minutes before other oral intake	1st-line bisphosphonate when fracture risk is significant.

Adjunct analgesia

Drug	Dosage	Adverse effects	Drug interactions	Comments
Acetaminophen	Adults: 325-1000 mg PO every 4-6 hours as needed, up to the labelled daily maximum	Hepatotoxicity at supratherapeutic doses	None significant at standard doses	An adjunct analgesic compatible with essentially every AS regimen; not a substitute for adequate continuous NSAID or biologic therapy.

References

Axial spondyloarthritis — The Lancet (Sieper J, Poddubnyy D.). Lancet 2017;390(10089):73-84
Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada Living Treatment Recommendations for the Management of Axial Spondyloarthritis — The Journal of Rheumatology, Canadian Rheumatology Association (Rohekar S, Pardo Pardo J, Mirza R, et al.). J Rheumatol 2025;52(1):10-22
New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS) — Annals of the Rheumatic Diseases (Sieper J, van der Heijde D, Landewé R, et al.). Ann Rheum Dis 2009;68(6):784-788
Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria — Arthritis & Rheumatism (van der Linden S, Valkenburg HA, Cats A.). Arthritis Rheum 1984;27(4):361-368
The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection — Annals of the Rheumatic Diseases (Rudwaleit M, van der Heijde D, Landewé R, et al.). Ann Rheum Dis 2009;68(6):777-783
ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update — Annals of the Rheumatic Diseases, ASAS/EULAR (Ramiro S, Nikiphorou E, Sepriano A, et al.). Ann Rheum Dis 2023;82(1):19-34

Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.