ArticleArthritis research & therapy2023
Joint-level responses to tofacitinib and methotrexate: a post hoc analysis of data from ORAL Start.
Article in Arthritis research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01039688 (Phase 3 Randomized, Double-blind Study Of The Efficacy And Safety Of 2 Doses Of Cp-690,550 Compared To Methotrexate In Methotrexate Navie Patients With Rheumatoid Arthritis), which is not on this map. Cited by 9 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 3 Randomized, Double-blind Study Of The Efficacy And Safety Of 2 Doses Of Cp-690,550 Compared To Methotrexate In Methotrexate Navie Patients With Rheumatoid Arthritis
Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Observational
- Location and amount of joint involvement differentiates rheumatoid arthritis into different clinical subsets.NPJ digital medicine · 2025Article
- Differential joint-level response to secukinumab in psoriatic arthritis: A collaborative European observational cohort study.EULAR rheumatology open · 2025Article
- Location-specific treatment of chronic inflammatory joint disease.Nature reviews. Rheumatology · 2025Article
- Differences in the response to TNF inhibitors at distinct joint locations in patients with psoriatic arthritis: results from nine European registries.Arthritis research & therapy · 2025Observational
- Machine learning-based prediction of response to Janus kinase inhibitors in patients with rheumatoid arthritis using clinical data.Frontiers in immunology · 2025Article
- Joint-specific rheumatoid arthritis fibroblast-like synoviocyte regulation identified by integration of chromatin access and transcriptional activity.JCI insight · 2024Article
- Joint-specific memory, resident memory T cells and the rolling window of opportunity in arthritis.Nature reviews. Rheumatology · 2024Review
- All fibroblasts are equal, but some are more equal than others.Nature reviews. Rheumatology · 2024Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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