The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial

Br J Dermatol. 2003 Feb;148(2):318-25. doi: 10.1046/j.1365-2133.2003.05173.x.


Background: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris.

Objectives: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX.

Methods: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well.

Results: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle).

Conclusions: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / analysis
  • Aspartate Aminotransferases / analysis
  • Calcitriol / administration & dosage*
  • Calcitriol / adverse effects
  • Calcitriol / analogs & derivatives*
  • Dermatologic Agents / administration & dosage*
  • Dermatologic Agents / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Middle Aged
  • Ointments
  • Pharmaceutical Vehicles
  • Psoriasis / drug therapy*
  • Psoriasis / enzymology
  • Severity of Illness Index


  • Dermatologic Agents
  • Ointments
  • Pharmaceutical Vehicles
  • calcipotriene
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Calcitriol
  • Methotrexate