Efficacy and Safety of a Combination Therapy of Methotrexate, Chloroquine and Cyclophosphamide in Patients with Refractory Rheumatoid Arthritis: Results of an Observational Study with Matched-Pair Analysis

Abstract

The efficacy and safety of a combination of methotrexate (MTX), chloroquine (CQ) and cyclophosphamide (CYC) were studied in patients with refractory rheumatoid arthritis. A single-centre, matched-pair observational study with prospectively gathered data was performed. Fifty-six patients who had previously failed with MTX were treated with 15 mg MTX per week, 50 mg CYC three times a week and 250 mg CQ per day (group A). A 50% improvement of the swollen joint count was required to continue therapy. Data were compared with the results of the previous MTX therapy in the same group and with a matched-patient cohort receiving MTX monotherapy for the first time (group B). In group A, the combination therapy resulted in a significant decline of the swollen joint count after 1 year, in contrast to the previous MTX monotherapy in the same group. Complete remission of joint swelling was achieved in 13 patients (23%), compared with 26 patients in group B (47%). The median duration of effective combination treatment in group A was significantly longer than preceding therapies with MTX alone (19 vs 13 months, p<0.05). However, patients in group B could be treated for a median of 57.5 months (p<0.0001 compared with group A). Side-effects were comparable in both groups. The applied DMARD combination is safe and beneficial in a significant proportion of patients if MTX monotherapy is ineffective.

Acute myeloid leukemia developing in patients with autoimmune diseases

“…39 Cyclophosphamide, a potent immunosuppressive agent whose use is restricted to severe cases of refractory rheumatoid arthritis, such as vasculitis, is known to be leukemogenic. 43 Three additional population based studies examined leukemia/cancer risk, in patients treated with anti-TNF agents. [40][41][42] The risk of hematologic cancers in patients treated with anti-TNF therapy was compared to patients treated with any non-biological disease modifying agent in one study 41 and to methotrexate-treated patients in another.…”

Risk factors of gastrointestinal and hepatic adverse drug reactions in the treatment of rheumatoid arthritis with biomedical combination therapy and Chinese medicine

“…According to the results of other clinical studies (Keyszer et al, 1999), all patients in WM group took the following drugs with the dosage and administration methods. Briefly, diclofenec extended action tablet, 75 mg once a day after meal, and was discontinued when the severe joint pain become controlled; MTX, once a week with a starting dosage at 5 mg with addition of 2.5 mg each week and maintain dosage about 5 mg a week; sulfasalazine, twice a day with the starting dosage at 0.25 g and additional 0.5 g/day, the maintain dosage ranging from 0.5 g to 1 g, four times a day.…”

“…Compared with other DMARDs, MTX has a relatively good safety profile (Chang et al, 1997;Keyszer et al, 1999), yet toxicity was still the major factor limiting the drugs' clinical use and the most common reasons for stoppages (Sandoval et al, 1995). Similarly, sulfasalazine is proved to be effective in the treatment of patients with RA, yet limited by adverse reactions in its use (Skosey, 1988 During MTX treatment, <45% of patients had discontinued the drug after 96 months, and for sulphasalazine, the time until 50% discontinued due to ADRs or inefficacy was 43.3 months (Grove et al, 2001).…”

The Predictive Role of Symptoms/signs on ACR20 Responses in Rheumatoid Arthritis Analyzed with Data Mining Approaches

“…WM therapy: Referring to other clinical studies [2][3][4], all patients took the following medicines (combination therapy in biomedicine). Declofenec extended action tablet, 75mg once a day, orally, after meal, and was discontinued when the severe joint pain become controlled.…”

“…Its worldwide prevalence is approximately 1% [1]. The combined therapy in Western medicine (WM) seems to be effective [2][3][4]. CM is widely used in China and was found to be effective in the treatment of RA even without consideration of CM pattern classification.…”