Thalidomide for severe refractory ankylosing spondylitis: a 6-month open-label trial

OBJECTIVE: To examine the efficacy of thalidomide in the treatment of active ankylosing spondylitis (AS) refractory to conventional therapies. METHODS: In a 6-month open-label trial, we studied 13 men with different subtypes of active AS: 3 juvenile AS, 9 adult AS, and one AS with psoriasis. All patients were resistant to conventional nonbiologic therapies including nonsteroidal antiinflammatory drugs, sulfasalazine, and methotrexate. After 3 months' observation on a preexisting regimen, oral thalidomide was added, starting at 100 mg/day for 1 week, then 200 mg/day for another 23 weeks. Outcome measures included the Bath AS Disease Activity Index (BASDAI), Functional Index (BASFI), Global Index (BAS-G), IgA, C-reactive protein (CRP), and eosinophil sedimentation rate (ESR). Response to treatment was defined following the Ankylosing Spondylitis Assessment criteria. RESULTS: Three patients withdrew due to rash. Two patients were lost to followup due to lack of efficacy. Eight patients completed the trial. Four patients attained > 50% improvement (2 juvenile AS, 1 peripheral AS, and 1 psoriatic arthritis). Four patients attained > 20% improvement (2 axial and 2 peripheral AS). Total response rate accordingly was 80% (8/10). Mean BASDAI improved significantly from baseline to Week 24 (4.97 vs 3.1; p = 0.0156). Mean BASFI improved from baseline to Week 24 (5.24 vs 3.06; p = 0.0078), and BAS-G from 6.02 to 3.21 (p = 0.0078). Significant laboratory improvements were found in ESR (from 69.5 to 34.2 mm/h; p = 0.0156), but not CRP (from 6.08 to 3.01 mg/dl; p = 0.078) or IgA (from 496 to 505 mg/dl; p = 0.375). Dry mouth, constipation, and dizziness were common, but no severe adverse events were found. CONCLUSION: Thalidomide is a promising treatment for patients with active AS who are resistant to conventional therapies other than biologics.