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


OBJECTIVE
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.
de Jong
E M G J
EM
Department of Dermatology, University Hospital Center St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands. e.dejong@derma.wncn.nl
Mørk
N J
NJ
Seijger
M M B
MM
De La Brassine
M
M
Lauharanta
J
J
Jansen
C T
CT
Guilhou
J J
JJ
Guillot
B
B
Ostrojic
A
A
Souteyrand
P
P
Vaillant
L
L
Barnes
L
L
Rogers
S
S
Klaber
M R
MR
Van De Kerkhof
P C M
PC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000032:analysis; D002117:Calcitriol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009824:Ointments; D014677:Pharmaceutical Vehicles; D011565:Psoriasis / Q000188:drug therapy* / Q000201:enzymology; D012720:Severity of Illness Index
D003879:Dermatologic Agents; D009824:Ointments; D014677:Pharmaceutical Vehicles; C055085:calcipotriene; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002117:Calcitriol; D008727:Methotrexate