Joint-level responses to tofacitinib and methotrexate: a post hoc analysis of data from ORAL Start

Arthritis Research & Therapy

Research

Caroline Ospelt¹  Adrian Ciurea¹  Oliver Distler¹  Mojca Frank Bertoncelj²  Tim Killeen³  Lisy Wang⁴  Kenneth Kwok⁵  Hyejin Jo⁵ 

[1] Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland;Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland;BioMed X Institute, Heidelberg, Germany;Inflammation & Immunology, Pfizer AG, Schärenmoosstrasse 99, 8052, Zürich, Switzerland;Inflammation & Immunology, Pfizer Inc., Groton, CT, USA;Inflammation & Immunology, Pfizer Inc., New York, NY, USA;

关键词: Tofacitinib;    Rheumatoid arthritis;    Methotrexate;    Radiographic;    Joint;   

DOI  :  10.1186/s13075-023-03144-1

 received in 2022-11-17, accepted in 2023-08-23,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRheumatoid arthritis (RA) has a variable impact on different synovial joints, with inflammation being more commonly observed in some joints than others. Emerging evidence suggests that the anatomical variation in pathophysiology could result in differential responses to treatments across the joints, both within and between modes of action. This analysis aimed to characterize joint-specific responses to tofacitinib and methotrexate monotherapy in patients with RA.MethodsThis was a post hoc analysis of data from the phase III trial ORAL Start (NCT01039688), in methotrexate-naïve patients with RA. A paired joint pathology score (PJPS), derived from bilateral tender/swollen joint counts, was calculated. The percentage change from baseline in PJPS (%∆PJPS) and treatment-specific responses (tofacitinib 5 and 10 mg twice daily [BID] vs methotrexate; tofacitinib 5 vs 10 mg BID) for each patient joint pair, except for those with baseline/post-baseline PJPS = 0, were calculated at month 3, month 6, and month 12. Radiographic progression was similarly assessed using the Modified Total Sharp Score at month 6 and month 12.ResultsIn methotrexate-naïve patients, differences in %∆PJPS demonstrated greater responses with tofacitinib vs methotrexate in most joint locations. Lesser responses with tofacitinib vs methotrexate were observed in most joints of the feet, particularly at month 12. Despite this, radiographic progression at month 12 was significantly worse in the foot (and metacarpophalangeal) joints of patients receiving methotrexate vs tofacitinib.ConclusionWe observed variation in joint-specific responses with tofacitinib and methotrexate monotherapy. Despite a proximal–distal efficacy gradient, with better clinical responses in the feet, patients receiving methotrexate monotherapy demonstrated more radiographic progression in the foot joints compared with those receiving tofacitinib. These findings suggest that body site- and therapy-specific characteristics may interact to produce differential treatment responses.Trial registrationClinicalTrials.gov, NCT01039688.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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