title: Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, USA. aksingal@uab.edu
authors.forename: Ashwani K
authors.initials: AK
authors.lastname: Singal
authors.forename: Csilla
authors.initials: C
authors.lastname: Kormos-Hallberg
authors.forename: Chul
authors.initials: C
authors.lastname: Lee
authors.forename: Vaithamanithi M
authors.initials: VM
authors.lastname: Sadagoparamanujam
authors.forename: James J
authors.initials: JJ
authors.lastname: Grady
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Freeman
authors.forename: Karl E
authors.initials: KE
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy / Q000009:adverse effects / Q000379:methods*; D010949:Plasma / Q000737:chemistry; D017119:Porphyria Cutanea Tarda / Q000188:drug therapy* / Q000601:surgery*; D011166:Porphyrins / Q000097:blood; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D011166:Porphyrins; D006886:Hydroxychloroquine