Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda

Abstract

Background & aims: Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase; it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies.

Methods: We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine.

Results: The time to remission was a median 6.9 months for patients who received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 mo for randomized patients), a difference that was not significant (log-rank, P = .06 and P = .95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio, 2.19; 95% confidence interval, 0.95-5.06) for all patients. Patients who received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment.

Conclusions: Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. ClinicalTrials.gov number, NCT01573754.

Figure 1

Enrollment, assignment to treatment with or without randomization of 48 study patients with porphyria cutanea tarda, and inclusion of the 30 patients who achieved a normal plasma porphyrin concentration in the analysis comparing time to remission with phlebotomy and low dose hydroxychloroquine.

Figure 2

Cumulative probability of time to remission, defined as achieving a normal plasma porphyrin concentration, of 30 patients with porphyria cutanea tarda treated by phlebotomy (n=17, black line) or low-dose hydroxychloroquine (n=13, gray line). The median time to remission was somewhat shorter with hydroxychloroquine than with phlebotomy [6.1 vs. 6.9 months; Log Rank P=0.06]

Figure 3

Cumulative probability of time to remission of 17 patients with porphyria cutanea tarda randomized to treatment by phlebotomy (n=7, black line) or low-dose hydroxychloroquine (n=10, gray line). The median time to remission was similar with hydroxychloroquine and with phlebotomy [6.5 vs. 6.7 months; Log Rank P=0.95].