What treatment options are available for a patient with ankylosing spondylitis (AS), chronic kidney disease (CKD) stage 3a, and a history of frequent urinary tract infections (UTIs) who cannot tolerate biologic Disease-Modifying Antirheumatic Drugs (DMARDs)?

Treatment Options for Ankylosing Spondylitis with CKD 3a and Recurrent UTIs After bioDMARD Intolerance

For a patient with AS who cannot tolerate biologic DMARDs due to frequent UTIs and has CKD stage 3a, NSAIDs remain the cornerstone of treatment with careful monitoring, combined with physical therapy, while avoiding conventional DMARDs for axial disease. 1

Primary Treatment Strategy: NSAIDs with Renal Precautions

NSAIDs are recommended as first-line drug treatment for AS patients with pain and stiffness, even in the presence of CKD 3a, though dose reduction is required. 1

• For patients with CKD 3a, reduce NSAID dosing to 5 mg once daily (for tofacitinib) or equivalent dose adjustments for other NSAIDs to minimize nephrotoxic effects while maintaining therapeutic benefit 2
• In patients with increased GI risk, use selective COX-2 inhibitors or non-selective NSAIDs plus gastroprotective agents (PPIs) to reduce serious GI complications (RR 0.18 for coxibs vs NSAIDs; RR 0.40 for PPIs) 1
• Monitor renal function closely as NSAIDs can worsen kidney disease, particularly in patients with pre-existing renal impairment 3, 4

Why This Approach Despite Renal Disease

The evidence shows NSAIDs provide convincing benefit for spinal pain, peripheral joint pain, and function in AS 5, and while nephrotoxicity is a concern 3, 4, complete avoidance leaves patients with limited effective options when biologics are contraindicated due to infection risk.

Essential Non-Pharmacological Management

Physical therapy and regular exercise must be initiated immediately as they form the cornerstone of AS treatment and can provide meaningful benefit even without optimal pharmacologic therapy. 1, 5, 6

• Structured, active land-based exercise programs are preferred over passive modalities 6, 7
• Individual and group physical therapy should both be considered, with group therapy showing better patient global assessment outcomes 5
• Patient education regarding disease management and self-care strategies 1, 5

Adjunctive Pharmacological Options

Analgesics for Breakthrough Pain

Paracetamol (acetaminophen) and opioids may be considered for pain control when NSAIDs are insufficient or need to be minimized due to renal concerns. 1, 5

• Paracetamol shows no significant increase in GI toxicity compared to placebo (RR 0.80) 1
• Use cautiously in CKD, monitoring for accumulation 1

Local Corticosteroid Injections

Corticosteroid injections directed to local sites of musculoskeletal inflammation (sacroiliac joints, peripheral joints, entheses) may be beneficial. 1, 5, 6

• Intra-articular or periarticular injections for active sacroiliitis or peripheral arthritis 1, 6
• Avoid systemic corticosteroids for axial disease as they are strongly contraindicated and lack evidence of efficacy 1, 6, 7

What NOT to Use

Conventional DMARDs Are Ineffective for Axial Disease

There is no evidence for efficacy of conventional DMARDs including sulfasalazine and methotrexate for treatment of axial disease in AS. 1, 6

• Sulfasalazine may only be considered if peripheral arthritis is present, but shows no benefit for spinal symptoms 1, 8
• The pooled analysis shows sulfasalazine only reduces ESR (WMD -4.79 mm/h) and morning stiffness (WMD -13.89 on VAS-100), with no benefit in physical function, pain, or spinal mobility 8
• Sulfasalazine carries significant toxicity risk (RR 2.37 for any adverse event, RR 4.01 for hematological events) 1

Biologic DMARDs: Contraindicated in This Patient

While anti-TNF treatment and IL-17 inhibitors are normally recommended for persistently high disease activity despite NSAIDs, they are contraindicated in this patient due to recurrent UTIs. 1, 7

• TNF inhibitors increase infection risk (RR 1.07 for any infection) 1
• Patients with recurrent infections, indwelling urinary catheters, or persistent/recurrent chest infections are at high risk and should not receive biologics 1
• The patient's frequent UTIs represent an absolute contraindication to immunosuppressive biologic therapy 1

Alternative Biologic: JAK Inhibitor Consideration

Tofacitinib (XELJANZ) is FDA-approved for AS in patients with inadequate response or intolerance to TNF blockers, but carries similar infection risks and requires dose adjustment for CKD 3a. 2

• Reduce dose to 5 mg once daily in patients with moderate or severe renal impairment 2
• However, JAK inhibitors carry significant warnings including increased risk of serious infections, malignancy, MACE, and thrombosis, particularly in patients ≥50 years with cardiovascular risk factors 2
• Given this patient's recurrent UTIs, JAK inhibitors are likely also contraindicated due to similar immunosuppressive effects 2

Monitoring Requirements

Regular disease activity assessment using validated measures (BASDAI score >4 indicates high disease activity) and monitoring of renal function, inflammatory markers (ESR, CRP), and infection surveillance. 1, 5, 7

• Monitor absolute lymphocyte count, absolute neutrophil count, and hemoglobin if any immunosuppressive therapy is considered 2
• Assess for UTI symptoms at each visit and treat infections promptly before they become serious 1

Critical Pitfalls to Avoid

Do not use systemic corticosteroids for axial disease despite their common use in other rheumatic conditions—they lack evidence and carry significant adverse effects 1, 6, 7

Do not prescribe conventional DMARDs (sulfasalazine, methotrexate) for predominant axial symptoms as they are ineffective for spinal disease 1, 6, 7, 8

Do not completely avoid NSAIDs solely due to CKD 3a—instead, use reduced doses with close monitoring, as they remain the most effective pharmacologic option when biologics are contraindicated 1, 2

Do not ignore the infection risk when considering any immunosuppressive therapy in a patient with recurrent UTIs 1, 2

Realistic Expectations

Without access to biologic DMARDs, symptom control will be limited compared to standard AS management, and the primary goals shift to maintaining function and preventing deformity through physical therapy combined with carefully monitored NSAID therapy. 6

• Physical therapy alone can provide meaningful benefit for pain, stiffness, and function, though less than combined pharmacologic approaches 5, 6
• The treatment strategy prioritizes quality of life and functional preservation while avoiding life-threatening infections that could result from immunosuppression in the setting of recurrent UTIs and CKD 6, 3