Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials - 23/11/17
, Murali Sundaram, PhD c, James E. Signorovitch, PhD b, Junlong Li, PhD b, Meng Xie, BS b, Eric Q. Wu, PhD b, Martin M. Okun, MD, PhD c, dAbstract |
Background |
Most methotrexate-treated psoriasis patients do not achieve a long-term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment.
Objective |
To develop a prediction rule to identify patients unlikely to respond adequately to methotrexate.
Methods |
Patient-level data from CHAMPION (NCT00235820, N = 110) was used to construct a prediction model for week 16 PASI75 by using patient baseline characteristics and week 4 PASI25. A prediction rule was determined on the basis of the sensitivity and specificity and validated in terms of week 16 PASI75 response in an independent validation sample from trial M10-255 (NCT00679731, N = 163).
Results |
PASI25 achievement at week 4 (odds ratio = 8.917) was highly predictive of response with methotrexate at week 16. Patients with a predicted response probability <30% were recommended to discontinue methotrexate. The rates of week 16 PASI75 response were 65.8% and 21.1% (P < .001) for patients recommended to continue and discontinue methotrexate, respectively.
Limitations |
The CHAMPION trial excluded patients previously treated with biologics, and the M10-255 trial had no restrictions.
Conclusion |
A prediction rule was developed and validated to identify patients unlikely to respond adequately to methotrexate. The rule indicates that 4 weeks of methotrexate might be sufficient to predict long-term response with limited safety risk.
Le texte complet de cet article est disponible en PDF.Key words : discontinuation, methotrexate, moderate-to-severe psoriasis, Psoriasis Area and Severity Index (PASI), prediction, response
Abbreviations used : AUC, DLQI, ITT, PASI, PASI25, PASI75, PGA, PROs, PtGA, ROC, VAS
Plan
| Funding sources: Supported by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the manuscript. |
|
| Conflicts of interest: Dr Gordon receives research support from AbbVie, Amgen, Jannsen, Eli Lilly, Boerhinger Ingelheim, Dermira, and Celgene and serves as consultant for AbbVie, Amgen, Boerhinger Ingelheim, Jannsen, Eli Lilly, Celgene, Pfizer, Sun Pharmaceuticals, and Novartis. Drs Betts, Signorovitch, Li, and Wu and Ms Xie are employed by Analysis Group Inc, which received payment from AbbVie Inc for participation in this research. Dr Sundaram is a former employee of AbbVie and may own AbbVie stock or stock options. Dr Okun is a former employee of AbbVie and serves as a consultant for AbbVie, Gilead Science, and Crescendo Biosciences. |
Vol 77 - N° 6
P. 1030-1037 - décembre 2017 Retour au numéro
Article précédent
- Cardiovascular comorbidities of pediatric psoriasis among hospitalized children in the United States
- Lauren Kwa, Michael C. Kwa, Jonathan I. Silverberg
- Uncovering burden disparity: A comparative analysis of the impact of moderate-to-severe psoriasis and hidradenitis suppurativa
- Iltefat H. Hamzavi, Murali Sundaram, Cynthia Nicholson, Marko Zivkovic, Angela Parks-Miller, Jianyi Lee, Jingbo Yi, Yihua Gu, Martin M. Okun, Arijit Ganguli, Steve R. Arikian
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?