What medications are most useful for preventing progression of bone disease in a patient with ankylosing spondylitis (ank spon) and a history of chronic opioid use, post posterior spinal fusion from C2 to the upper thoracic spine with posterior bone graft from C2-C7?

Medications for Prevention of Disease Progression in Ankylosing Spondylitis Post-Spinal Fusion

For preventing progression of ankylosing spondylitis in this post-surgical patient with chronic opioid use, continuous NSAIDs are the primary disease-modifying medication, with anti-TNF therapy reserved for persistently high disease activity despite NSAIDs, while simultaneously implementing a multimodal strategy to taper and discontinue opioids given their association with worse surgical outcomes and lack of disease-modifying properties. 1

Primary Disease-Modifying Strategy: NSAIDs

Continuous NSAID therapy is the only pharmacological intervention with evidence for retarding radiographic disease progression in ankylosing spondylitis. 1

• NSAIDs are recommended as first-line drug treatment for AS patients with pain and stiffness, with Level Ib evidence showing improvement in spinal pain, peripheral joint pain, and function 1
• Continuous treatment with NSAIDs is preferred over intermittent "on demand" use for patients with persistently active, symptomatic disease 1
• A randomized controlled trial comparing continuous versus intermittent celecoxib demonstrated that continuous treatment retards radiographic disease progression at 2 years—the first study showing a possible disease-modifying effect 1
• Short-term NSAID use (<2 weeks) appears safe even after spinal fusion, with no level 1 evidence linking NSAID use to reduced fusion rates in human studies 1

NSAID Selection Considerations

• COX-2 inhibitors (celecoxib) provide anti-inflammatory effects without increased bleeding risk and may be preferred in the post-surgical period 1
• Cardiovascular, gastrointestinal, and renal risks must be assessed when prescribing NSAIDs 1
• In patients with increased GI risk, use non-selective NSAIDs plus gastroprotective agents or selective COX-2 inhibitors 1

Anti-TNF Therapy for Refractory Disease

Anti-TNF therapy should be initiated if disease activity remains persistently high despite continuous NSAID treatment. 1

• Anti-TNF agents (infliximab, etanercept, adalimumab, golimumab) show large benefits in pain and function with Level Ib evidence 1
• There is no evidence requiring obligatory use of conventional DMARDs before anti-TNF therapy in patients with axial disease 1
• All TNF inhibitors show equivalent efficacy for axial and articular/entheseal manifestations, though gastrointestinal efficacy differs if inflammatory bowel disease is present 1
• Switching to a second TNF blocker may be beneficial in patients with loss of response 1

Medications WITHOUT Evidence for Axial Disease Progression

Conventional DMARDs including sulfasalazine and methotrexate have no evidence for efficacy in treating axial disease in AS. 1

• Sulfasalazine may only be considered for peripheral arthritis manifestations 1
• There is no evidence supporting biological agents other than TNF inhibitors in AS 1

Critical Management of Chronic Opioid Use

This patient's chronic opioid use is a significant risk factor for poor surgical outcomes and must be addressed, as opioids provide no disease-modifying benefit for AS. 1, 2

Evidence Against Continued Opioid Use

• Preoperative chronic opioid use (≥250 days) is associated with dramatically increased odds of postoperative long-term opioid use (OR 220,95% CI 149-326) 1
• Chronic preoperative opioid use predicts worse 2-year outcomes including higher reoperation rates, emergency department visits, wound complications, and prolonged postoperative opioid use 1
• Opioid use in AS is associated with subjective measures (depression, BASDAI, BASFI) rather than objective inflammatory markers (CRP, ESR), suggesting pain derives from sources other than spinal inflammation 2
• Chronic preoperative opioids are an independent risk factor for revision surgery (OR 1.453) and increased nonunion rates after lumbar fusion 3

Opioid Tapering Strategy

Implement multimodal non-opioid pain management to facilitate opioid discontinuation: 4

• Gabapentinoids (pregabalin 150-300 mg or gabapentin >900 mg/day) started preoperatively and continued postoperatively significantly reduce pain scores, opioid consumption, and improve long-term functional outcomes 1, 4
• Pregabalin at 300 mg has demonstrated effectiveness in managing opioid-refractory pain in AS patients while facilitating opioid discontinuation without withdrawal symptoms 5
• NSAIDs and acetaminophen should be administered continuously throughout the perioperative period as the foundation of pain management 4
• COX-2 inhibitors provide superior pain control with decreased postoperative nausea, vomiting, and greater patient satisfaction 1
• Local anesthetic wound infiltration with liposomal bupivacaine provides extended pain relief up to 96 hours 4

Strict Opioid Limitations if Continued

If opioids cannot be immediately discontinued: 4

• Maximum duration of 7 days or less postoperatively 4
• Prescribe immediate-release opioids at the lowest effective dose 4
• Review state PDMP data before prescribing 4
• Avoid concurrent benzodiazepines 4
• Evaluate benefits and harms within 1-4 weeks, then every 3 months 4

Non-Pharmacological Disease Management

Regular exercise and physical therapy are essential components of AS management throughout the disease course. 1

• Physical therapy with supervised exercises (land or water-based, individual or group) is more effective than home exercises alone 1
• Active supervised exercises focusing on core strengthening and spinal stabilization provide effective pain relief for 2-18 months 4
• Patient education and involvement with patient associations may be beneficial 1

Monitoring Parameters

• Disease activity assessment using BASDAI 2
• Functional status using BASFI 2
• Inflammatory markers (CRP, ESR) to guide anti-TNF therapy decisions 2
• Regular assessment of cardiovascular risk factors given increased cardiovascular disease risk in AS 1
• Bone density monitoring for osteoporosis risk, particularly given spinal fusion and potential glucocorticoid exposure 1

Common Pitfalls to Avoid

• Do not continue opioids long-term as they are associated with worse outcomes and provide no disease-modifying benefit in AS 1, 2
• Do not use systemic glucocorticoids for axial disease as there is no evidence supporting their use 1
• Do not require conventional DMARD trial before anti-TNF therapy in axial disease, as this delays effective treatment without evidence of benefit 1
• Do not use intermittent "on-demand" NSAIDs when continuous therapy may provide disease-modifying benefits 1