BERLIN — Psoriasis patients who show less than a PASI-50 response to 20 mg/wk of methotrexate by week 12 are unlikely to benefit from dosage increases or longer therapy, according to a new analysis of the CHAMPION study.
Week 12 has been found to be a useful decision point for discontinuing methotrexate and moving on to a biologic agent, said Dr. Jean-Hilaire Saurat, professor of dermatology at the University of Geneva.
“With the data we've obtained with CHAMPION, our understanding of how the treatment should be conducted should be reconsidered. We know that probably by week 12 we should know if the patient will respond or not,” said Dr. Saurat.
CHAMPION (Comparative Study of Adalimumab vs. Methotrexate vs. Placebo in Patients With Psoriasis) was a phase III, 16-week, double-blind, randomized trial in patients with moderate to severe psoriasis (Br. J. Dermatol. 2008;158:558–66).
The study provides the only existent placebo-controlled methotrexate data, noted Dr. Suarat, who presented the post hoc subanalysis results at the annual congress of the European Academy of Dermatology and Venereology.
CHAMPION included 103 evaluable patients randomized to 7.5 mg of oral methotrexate once weekly for 2 weeks, 10 mg weekly for the next 2 weeks, and then 15 mg/wk for 4 weeks.
The 40 patients with at least a PASI-50 response after 8 weeks—that is, a 50% reduction from baseline in Psoriasis Area and Severity Index scores—were deemed early responders. They remained on methotrexate 15 mg/wk for the rest of the 16-week study.
Patients with less than a PASI-50 at week 8 had their dosage increased to 20 mg/wk for 4 weeks. If at week 12 they had achieved a PASI-50 response they stayed on 20 mg/wk for the final 4 weeks of the study; if not, their dosage was increased to 25 mg/wk.
The 22 participants who reached PASI-50 after 8 weeks at dosages greater than 15 mg were classified as late responders; the 41 who never attained PASI-50 were deemed late nonresponders.
The mean weekly methotrexate dosage at 16 weeks was 14.5 mg in early responders, 19.5 mg in late responders, and 23.2 mg in late nonresponders. After 16 weeks, 27% of subjects had a PASI-75 response on a maximum dose of 15 mg/wk.
“The good news is in the responders the response to methotrexate is as good as to a biologic like adalimumab [Humira]. There is a group of patients on methotrexate who are extremely happy, and you do not need high doses to reach this response,” Dr. Saurat said.
The new findings from CHAMPION will be particularly useful for European physicians because psoriasis patients who require systemic therapy have to be treated with methotrexate before biologics can be considered, he suggested.
Audience member Dr. Craig L. Leonardi pointed out that methotrexate is still widely prescribed in the United States as well.
“I use methotrexate a lot these days. I've got hundreds of patients on it…. There's clearly a group of patients who do very well with this drug at low doses. It would be spectacular if we could predict which ones,” said Dr. Leonardi of the department of dermatology at Saint Louis University.
Unfortunately, Dr. Saurat said, no baseline predictors of early response in CHAMPION could be identified. Of note, however, patients destined for early responder status at week 8 already had a mean 40% reduction in PASI scores after just 4 weeks on methotrexate at 15 mg/wk.
The CHAMPION trial was sponsored by Abbott, which manufactures adalimumab. Dr. Saurat is an adviser to the company. Dr. Leonardi has served as a consultant to manufacturers of biologic agents for psoriasis.
'The good news is in the responders the response to methotrexate is as good as to a biologic like adalimumab.'
Source Dr. Saurat
'There's clearly a group of patients who do very well with this drug [methotrexate] at low doses.'
Source Dr. Leonardi
Source Elsevier Global Medical News