Spondyloarthritis – Comprehensive Therapeutic & Monitoring Notes

Spondyloarthritis (SpA): Core Concepts

• Chronic, immune-mediated group of arthropathies sharing:
  • Strong HLA-B27 association
  • Axial disease (sacro-iliitis, spondylitis)
  • Peripheral, asymmetrical, pauci-articular arthritis (lower limbs predominance)
  • Typical features: enthesitis, dactylitis, acute anterior uveitis (AAU)
  • Frequent extra-rheumatological manifestations (ERM): psoriasis, inflammatory bowel disease (IBD), AAU
• ASAS subdivision
  • Axial SpA (axSpA): radiographic (Ankylosing Spondylitis, AS) vs. non-radiographic (nr-axSpA)
  • Peripheral SpA (pSpA): arthritis, enthesitis and/or dactylitis; Psoriatic Arthritis (PsA) is the commonest form

Classification & Diagnosis

Axial SpA (ASAS criteria)

• Age at back-pain onset $<45\text{ yr}$ AND symptoms $>3\text{ mo}$
• Either:
  1. Sacro-iliitis on imaging + ≥1 SpA feature
  2. $\text{HLA-B27}^+$ + ≥2 SpA features

Peripheral SpA

• Peripheral arthritis, enthesitis or dactylitis WITH ≥1 of: psoriasis, IBD, preceding infection, HLA-B27, sacro-iliitis on imaging, uveitis, positive family history

Disease-Activity Assessment Tools

• BASDAI (0-10), response = $\ge50\%$ or $\ge2$ point drop (“BASDAI 50”)
• ASDAS = weighted index incorporating BASDAI items + CRP/ESR. Cut-offs:
  • $<1.3$ inactive
  • $1.3–2.1$ low
  • $2.1–3.5$ high
  • $>3.5$ very high
• ASAS 20/40/PR composite responses; ASAS 40 = $\ge40\%$ + $\ge2$ units improvement in ≥3/4 core domains & no worsening in the 4th

Non-Pharmacological Management (all SpA)

• Daily home exercises + weekly supervised physiotherapy
  • Goal: maintain spinal extension/rotation, prevent flexion deformity, enhance muscle strength, reduce CV risk
• Lifestyle:
  • Smoking cessation ↓ radiographic progression & CV events
  • Regular aerobic sports (swim, cycle)
• Therapeutic education addressing disease, treatments, self-help, psychosocial aspects

Pharmacological Management – Axial SpA

NSAIDs

• First-line, cornerstone; onset 48-72 h; ~70-80 % achieve good/very good response
• Continuous use (high ASAS-NSAID score >50) may slow mSASSS progression in CRP-high subgroup, but evidence conflicting
• Selective COX-2 (celecoxib, etoricoxib) ↓ GI ulcer risk; all agents (except possibly naproxen) ↑ cardiovascular risk
• GI protection with PPI; tailor dosing (long-acting evening dose if nocturnal pain)

Glucocorticoids

• Systemic: no meaningful effect on axial disease; avoid routine use
• Intra-articular: useful for peripheral joints, enthesitis, & sacro-iliac injection (≈80 % response; 40 mg triamcinolone; imaging guidance ↑ efficacy)

csDMARDs

• No role in pure axial disease
• Sulfasalazine considered ONLY for peripheral arthritis; minimal/absent axial benefit
• Methotrexate, leflunomide, ciclosporin ineffective for axial component
• Bisphosphonates: inconsistent; not recommended

bDMARDs & tsDMARDs

TNF inhibitors (5 agents)

• Infliximab (IV 5 mg/kg 0,2,6 → q6-8w), Etanercept (SC 50 mg weekly), Adalimumab (SC 40 mg q2w), Golimumab (SC 50 mg monthly), Certolizumab (SC 400 mg 0,2,4 → 200 mg q2w)
• Indications: active axSpA despite ≥2 NSAIDs (≥4 w), BASDAI ≥4 or ASDAS ≥2.1, objective inflammation (MRI / CRP)
• Efficacy: ~50 % ASAS 40; MRI inflammation reduction; potential structure-modifying if started <10 yr disease & maintained ≥4 yr
• Discontinuation ⇒ universal relapse; dose/interval tapering feasible in sustained remission

IL-17 inhibitors

• Secukinumab (SC 150 mg wk 0–4 then monthly; 300 mg for TNFi failures)
• Ixekizumab (SC 80 mg q2–4w)
• ~40–45 % ASAS 40 at 16 w; approved for radiographic & nr-axSpA

JAK inhibitor

• Upadacitinib 15 mg PO daily; SELECT-AXIS-1: superior to placebo at 14 w on ASAS 40/BASDAI 50; monitor for infections, HZV, VTE

Treatment Algorithm (ASAS/EULAR 2016)

1. Non-pharm + full-dose NSAID
2. If high activity persists ≥4 w → TNFi (or IL-17i)
3. Switch within/between classes on failure/intolerance
4. Monitor q3–6 mo; stop after 12 w if no BASDAI 50 or $\Delta\text{ASDAS}<1.1$

Safety & Screening

• Baseline: TB (TST/IGRA + CXR), HBV, HCV, HIV, CBC, LFT, CVD assessment
• Contra-indications: NYHA III–IV CHF, demyelinating disease, active malignancy
• Live vaccines contraindicated during therapy
• Pregnancy: certolizumab minimal placental transfer; may continue until conception, consider through pregnancy; safe in breastfeeding
• Slight ↑ non-melanoma skin cancer risk ⇒ annual skin check

Peripheral SpA & Psoriatic Arthritis (PsA)

Domains & Targets

• Musculoskeletal: peripheral arthritis, axial, enthesitis, dactylitis
• Skin/nail psoriasis
• Composite targets
  • Minimal Disease Activity (MDA) – 5/7 criteria
  • DAPSA: $\text{Tender}<em>{68}+\text{Swollen}</em>{66}+\text{Pain\ VAS}+\text{PtGlobal}+\text{CRP}$; remission $\le4$
  • ACR 20/50/70 in trials

Step-wise Management (EULAR 2019)

1. NSAIDs ± local GC injection (<7.5 mg PO short-term)
2. csDMARD (methotrexate anchor; leflunomide, sulfasalazine, ciclosporin) if peripheral disease
3. If inadequate after 3–6 mo or poor prognosis → bDMARD/tsDMARD choice guided by domain & comorbidities

b/tsDMARD Options & Domain Strengths

• TNFi: global joint, skin, enthesitis, dactylitis; structural protection
• IL-17i (secukinumab, ixekizumab, bimekizumab*): superior skin; joint and axial efficacy
• IL-12/23 or IL-23 (ustekinumab, guselkumab): skin + peripheral joints; limited axial data
• PDE-4 inhibitor: apremilast 20–30 mg BID; modest efficacy; favourable safety; GI tolerance
• JAKi: tofacitinib 5 mg BID, upadacitinib 15 mg QD; improve ACR 20/50/70; monitor serious infection, HZV, VTE (10 mg BID tofacitinib restricted)
• Abatacept 125 mg SC weekly: peripheral joints & structural benefit; minimal skin effect

IBD-Associated SpA

• NSAIDs with caution (short course; celecoxib safest)
• Sulfasalazine helpful for peripheral joints + colitis
• Immunosuppressants: azathioprine, methotrexate for gut but limited SpA effect
• TNFi monoclonal antibodies (infliximab, adalimumab; golimumab for UC; certolizumab for CD) treat both gut & joints
• Etanercept ineffective for IBD; may trigger de-novo IBD
• Vedolizumab gut-selective; no joint benefit, may induce enthesitis
• Ustekinumab effective for moderate–severe CD; safe for joints
• IL-17i contraindicated/worsen IBD

Reactive Arthritis (ReA)

• Usually self-limiting (resolution within 6–12 mo)
• Treatment: NSAIDs ± intra-articular GC; csDMARD (sulfasalazine) if >4–6 mo persistent; azathioprine/methotrexate anecdotal
• Refractory cases: TNFi case-series positive; no RCT data
• Antibiotics only if active Chlamydia infection (10–14 d); long-term regimens ineffective except small doxycycline+rifampicin study

Acute Anterior Uveitis (AAU) Management in SpA

• Incidence: 30–40 % of axSpA; HLA-B27, disease duration risk factors
• Typical presentation: sudden unilateral pain, redness, photophobia; refer urgent to ophthalmology
• Local therapy: topical steroids + cycloplegics, subconjunctival steroids if needed
• Systemic prevention (≥3 flares/yr or flare at steroid taper)
  • Continuous NSAID
  • Sulfasalazine ↓ flares from 3.4 → 0.9/yr
  • Methotrexate/azathioprine used by ophthalmologists but little SpA value
  • TNFi: infliximab & adalimumab best (flare rate 3.4/100 pt-yr); etanercept modest (7.9/100 pt-yr); golimumab & certolizumab promising
  • IL-17i (secukinumab) phase 2 positive; evidence evolving
• Paradoxical uveitis described with etanercept; monitor closely

Choosing a Biologic by Extra-Articular Profile

Monitoring & Follow-up

• Clinical: BASDAI or ASDAS (same per patient), Pt Global, spinal mobility, enthesitis count
• Labs: CRP/ESR q3–6 mo; metabolic panel; lipid/HbA1c for JAKi
• Imaging: MRI or radiograph every 2 yr if clinical progression
• Decide continuation at 12 wk: BASDAI 50 or $\Delta\text{ASDAS}\ge1.1$ (clinically important) required
• Consider taper/interval extension in sustained remission ≥6–12 mo

Key Take-Home Messages

• Early diagnosis (delay currently 5–10 yr) enables prompt physiotherapy, NSAID optimization & timely biologic initiation
• NSAIDs remain first-line; continuous high-dose may retard structural damage in high-CRP patients but pursue symptom-adapted or low-dose regimen generally
• csDMARDs have niche roles (sulfasalazine for peripheral disease; methotrexate for PsA skin + joints)
• Biologic/targeted therapy choice should balance axial/peripheral dominance, EAMs, prior response, comorbidities & safety
• Systematic screening (TB, viral hepatitis, HIV), vaccination review & patient education are mandatory before b/tsDMARDs
• Extra-articular manifestations guide biologic selection: monoclonal TNFi for IBD/uveitis; IL-17 or IL-23 blockade for psoriasis-dominant disease
• Treat-to-Target with validated composite indices (BASDAI/ASDAS, DAPSA/MDA) improves outcomes in both axSpA & PsA