Abstract
OBJECTIVE—To investigate the therapeutic benefit of cyclosporin A (CSA) switching to hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). METHODS—Thirty four patients with RA who displayed residual inflammation and disability despite partial responses to prior maximal tolerated doses of methotrexate, were included. All were treated with a staged approach using CSA for 24 weeks to induce clinical improvement, followed by HCQ for 16 weeks to maintain the improvement. Seven ACR core set measures were evaluated every four to eight weeks. RESULTS—During a 40 week open trial, 27/34 patients completed the study. CSA treatment significantly reduced the tender joints score, swollen joints score, visual analogue pain scale, patient's or doctor's global assessment, patient's self assessed disability, and C reactive protein. Compared with the time of entry into the trial, patients who switched from CSA to HCQ still possessed significantly lower levels of most variables, determined at 28, 32, and 40 weeks. According to the ACR 20% improvement definition, 15/27 (56%) patients had improved at 24 weeks after CSA treatment, and 14/27 (52%) remained improved at 16 weeks after the change to HCQ. Frequent side effects, such as hypertrichosis, gastrointestinal trouble, and hypertension, were noted during CSA treatment, but most of these disappeared after switching to HCQ. The mean levels of blood pressure and serum creatinine were significantly increased during CSA treatment, but returned to normal after changing to HCQ. CONCLUSIONS—The data suggest that CSA switching to HCQ treatment may be an effective strategy for patients with RA partially responding to methotrexate, particularly those with toxicity due to CSA.
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Figure 1 .
Outcomes of treatment with cyclosporin A (CSA) followed by a switch to hydroxychloroquine (HCQ) in patients with rheumatoid arthritis. CSA 0 = study entry; CSA 8 = eight weeks after CSA treatment; CSA 16 = 16 weeks after CSA treatment; HCQ 0 = 24 weeks after CSA treatment; HCQ 4 = four weeks after switching to HCQ; HCQ 8 = eight weeks after switching to HCQ; HCQ 16 = 16 weeks after switching to HCQ. Data are means (SEM) at each week. *p<0.05, **p<0.01, and ***p<0.001 denote the significance of the differences in the ACR core set measures at the entry to the trial compared with during CSA or HCQ treatment.
Figure 2 .
Changes in blood pressure, blood urea nitrogen (BUN), and serum creatinine during the treatment with cyclosporin A (CSA) followed by a switch to hydroxychloroquine (HCQ). *p<0.05, **p<0.01, and ***p<0.001 denote the significance of differences in blood pressure, BUN, and serum creatinine at the entry to the trial versus during CSA or HCQ treatment, while †p<0.01 and ‡p<0.001 denote the significance of differences in the above variables at HCQ 0 versus HCQ 4, 8, or 16. See fig 1 for definitions.