A prediction rule was developed and validated to identify patients with psoriasis who are unlikely to respond adequately to methotrexate treatment. Based on this rule, 4 weeks of methotrexate therapy are sufficient to predict an individual’s long-term psoriasis outcomes with limited safety risk, according to the results of a retrospective analysis published in the Journal of the American Academy of Dermatology.1
It is well known that most patients treated with methotrexate do not achieve a long-term 75% reduction from baseline Psoriasis Area Severity Index score (PASI75) response. Often, indicators of nonresponse are apparent well after 4 weeks of methotrexate therapy.
Data from the phase 3 randomized double-blind CHAMPION trial2 (ClinicalTrials.gov identifier: NCT00235820; N=110), which compared treatments with adalimumab, oral methotrexate, and placebo for moderate to severe psoriasis, were used to construct a prediction model for achieving PASI75 at week 16 by using patient baseline characteristics and PASI25 scores at week 4.
This prediction rule, which was established based on sensitivity and specificity, was validated for week 16 PASI75 response in an independent validation sample from the phase 3, randomized, double-blind M10-255 trial (ClinicalTrials.gov identifier: NCT0067973; N=163), which compared methotrexate with briakinumab.3
Achieving PASI 25 at week 4 was highly predictive of methotrexate response after
16 weeks (odds ratio [OR], 8.917). Those patients who had a predicted response probability of <30% were advised to discontinue methotrexate treatment.
The rates of week 16 PASI75 response in patients recommended to continue and discontinue methotrexate were 68.8% (53 of 77 patients) and 16.3% (14 of 86 patients), respectively.
The investigators maintained that the use of this scoring algorithm to predict a patient’s response to methotrexate can help clinicians make informed treatment decisions regarding those individuals with psoriasis who might benefit from early switching to another agent in the longer term.
- Gordon KB, Betts KA, Sundaram M, et al. Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: evidence from 2 phase 3 clinical trials [published online October 6, 2017] J Am Acad Dermatol. doi:10.1016/j.jaad.2017.08.017
- Saurat JH, Stingl G, Dubertret L, et al; CHAMPION Study Investigators. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008;158(3):558-566.
- Reich K, Langley RG, Papp KA, et al. A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med. 2011;365(17):1586-1596.