Excellent endpoints from step-down bridge combination therapy of 5 immunosuppressants in NSAID-refractory ankylosing spondylitis: 6 year international study in Asia - WHO-ILAR COPCORD stage II treatment of the autoimmune diseases.
OBJECTIVE
To achieve induction and maintenance of remission in ankylosing spondylitis (AS) refractory to nonsteroidal antiinflammatory drugs with "step-down bridge combination" of 5 immunosuppressants, as an alternative to costly biologic DMARD. Primary endpoints were the percentage of patients achieving ASAS 20 at the end of Year 6; secondary endpoints were patients achieving ASAS 50 and ASAS 70, induction and maintenance of clinical and radiological remission, and the side effects of this combination of immunosuppressive drugs.


METHODS
In a 6-year uncontrolled international open-label prospective study, 54 men and 25 women with AS were enrolled after exclusion criteria were applied. Included patients were treated with individualized combinations of low-dose intravenous methylprednisolone + cyclophosphamide + methotrexate (for the first 6 mo). When erythrocyte sedimentation rate dropped to < or = 20 mm (men < or = 10 mm), low-dose oral mycophenolate mofetil and cyclosporine were prescribed for at least 2 years. Assessments were executed at baseline, Weeks 1 and 2; Months 1, 2, 4, and 6; and Years 1, 2, 4, and 6.


RESULTS
After 15/79 dropouts were accounted for, 64/79 patients achieved ASAS 20, ASAS 50, and ASAS 70. Disease remission occurred in 60/79 at 6 months when IV drugs were tapered. Gastrointestinal side effects were observed in 20/79 patients; no liver, renal, cardiovascular, and hematologic adverse effects were observed.


CONCLUSIONS
Step-down bridge combination of 5 immunosuppressants achieved ASAS 20, ASAS 50, and ASAS 70 in 64/79 patients, and remission in 60/79 patients with NSAID-refractory AS. Controlled studies are needed to confirm this method, and to study the role of these different drugs in developing countries in Asia, where the majority of patients with NSAID-refractory AS are unable to obtain treatment with tumor necrosis factor-alpha blockers.
Darmawan
John
J
WHO Collaborating Center, Community-Based Epidemiology, Prevention, and Treatment of Rheumatic Disease (COPCORD), Indonesia Rheumatic Center, Semarang-Jakarta, Indonesia. Jd131035@hotmail.com
Nasution
A Remy
AR
Chen
Shun-Le
SL
Haq
Syed Atiqul
SA
Zhao
Dongbao
D
Zeng
Qingyu
Q
Davatchi
Fereydoun
F
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000503:physiopathology; D006304:Health Status; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011859:Radiography; D012074:Remission Induction; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D014944:World Health Organization
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents