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
JOHN DARMAWAN, A. REMY NASUTION, SHUN-LE CHEN, SYED ATIQUL HAQ, DONGBAO ZHAO, QINGYU ZENG, and FEREYDOUN DAVATCHI
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 ≤ 20 mm (men ≤ 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.
Conclusion. 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-a blockers. (J Rheumatol 2006;33:2484-92)
Key Indexing Terms:
From the WHO Collaborating Center, Community-Based Epidemiology, Prevention, and Treatment of Rheumatic Disease (COPCORD), Indonesia Rheumatic Center, Semarang-Jakarta, Indonesia; Department of Rheumatology, Ren Ji Hospital, Shanghai Second Medical University, Shanghai, China; Rheumatology Wing, Department of Medicine, Bangabandhu Sheikh Mujib Medical University, Shahbagh, Dhaka, Bangladesh; Department of Rheumatology and Immunology, Changhai Hospital, Shanghai Second Military Medical University, Shanghai; Department of Rheumatology, Shantou University Medical College, Guangdong, China; and the Rheumatology Research Center, Shariati Hospital, Tehran, Iran.
J. Darmawan, MD, PhD; A.R. Nasution, MD (deceased), COPCORD, Indonesia Rheumatic Center; S-L. Chen, MD, Department of Rheumatology, Ren Ji Hospital, Shanghai Second Medical University; S.A. Haq, MD, Rheumatology Wing, Department of Medicine, Bangabandhu Sheikh Mujib Medical University; D. Zhao, MD, Department of Rheumatology and Immunology, Changhai Hospital, Shanghai Second Military Medical University; Q. Zeng, MD, Department of Rheumatology, Shantou University Medical College; F. Davatchi, MD, Rheumatology Research Center, Shariati Hospital.
Address reprint requests to Dr. J. Darmawan, Jalan Seroja Dalam 7, Semarang 50136, Indonesia. E-mail: Jd131035@hotmail.com
Accepted for publication July 18, 2006.