Abstract | INTRODUCTION: METHODS: The decision tree model GUIDE was trained using a data subset from the sarilumab trial with the most biomarker data, MOBILITY, to identify a rule to predict disease activity after sarilumab 200 mg. The training set comprised 18 categorical and 24 continuous baseline variables; some data were omitted from training and used for validation by the algorithm (cross-validation). The rule was tested using full datasets from four trials (MOBILITY, MONARCH, TARGET, and ASCERTAIN), focusing on the recommended sarilumab dose of 200 mg. RESULTS: In the training set, the presence of anti- cyclic citrullinated peptide antibodies, combined with C-reactive protein > 12.3 mg/l, was identified as the "rule" that predicts American College of Rheumatology 20% response (ACR20) to sarilumab. In testing, the rule reliably predicted response to sarilumab in MOBILITY, MONARCH, and ASCERTAIN for many efficacy parameters (e.g., ACR70 and the 28- joint disease activity score using CRP [DAS28-CRP] remission). The rule applied less to TARGET, which recruited individuals refractory to tumor necrosis factor inhibitors. The potential clinical benefit of the rule was highlighted in a clinical scenario based on MONARCH data, which found that increased ACR70 rates could be achieved by treating either rule-positive patients with sarilumab or rule-negative patients with adalimumab. CONCLUSIONS: Well-established and clinically feasible blood biomarkers can guide individual treatment choice. Real-world validation of the rule identified in this post hoc analysis is merited. CLINICAL TRIAL REGISTRATION: NCT01061736, NCT02332590, NCT01709578, NCT01768572.
|
Authors | Markus Rehberg, Clemens Giegerich, Amy Praestgaard, Hubert van Hoogstraten, Melitza Iglesias-Rodriguez, Jeffrey R Curtis, Jacques-Eric Gottenberg, Andreas Schwarting, Santos Castañeda, Andrea Rubbert-Roth, Ernest H S Choy, MOBILITY, MONARCH, TARGET, and ASCERTAIN investigators |
Journal | Rheumatology and therapy
(Rheumatol Ther)
Vol. 8
Issue 4
Pg. 1661-1675
(Dec 2021)
ISSN: 2198-6576 [Print] England |
PMID | 34519964
(Publication Type: Journal Article)
|
Copyright | © 2021. The Author(s). |