Treatment of refractory rheumatoid arthritis with low-dose cyclophosphamide. Long-term follow-up of 108 patients.
Although cyclophosphamide (CYC) is an effective drug in the treatment of refractory rheumatoid arthritis (RA), the application of this drug in RA has largely been abandoned, due to potentially life-threatening adverse events such as myelosuppression and cancer development. However, the question remains open, whether it is possible to balance the toxicity and the efficacy of CYC with low-dose therapy. 108 patients with refractory RA or with vasculitic organ involvement were treated with 50 mg CYC per day. Joint indices and laboratory parameters were gathered prospectively and the occurrence of serious side effects was monitored over a median of 10 years. The efficacy was surveyed in six months intervals. A 50% improvement of the swollen joint count was required to continue therapy. A long-term follow-up was performed to survey the incidence of malignancies. 85 patients dropped out within the first year. Only four patients were treated for longer than 4 years. In the total cohort, 50 patients were withdrawn due to the lack of efficacy, 34 patients had to discontinue because of adverse events, and 9 patients dropped out for both reasons. Gastrointestinal intolerance was the most frequent adverse event that led to the discontinuation of the drug, followed by myelosuppression. Five patients suffered from 6 malignancies occurring after a median of 4.5 years after cessation of treatment. Treatment of RA patients with 50 mg CYC per day resulted in a more favorable rate of serious adverse events and a markedly lower incidence of tumors compared to the treatment with 75 to 150 mg per day described in the literature. However, the long-term efficacy of this regimen was poor in our cohort.
Keysser
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Universitätsklinikum Charité, Medizinische Klinik und Poliklinik II, Berlin.
Keysser
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Keysser
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D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D003520:Cyclophosphamide