Evidence map›Paper›PMID 34103405›Full record

Trial reportRMD open2021

Efficacy and safety of tofacitinib modified-release 11 mg once daily plus methotrexate in adult patients with rheumatoid arthritis: 24-week open-label phase results from a phase 3b/4 methotrexate withdrawal non-inferiority study (ORAL Shift).

Stanley B Cohen, Janet Pope, Boulos Haraoui, Eduardo Mysler, Annette Diehl, Tatjana Lukic, Shixue Liu, Lori Stockert, Rebecca Germino, Sujatha Menon and 2 more

Registry-linked trialAbstract readClinical Trial, Phase IIIRandomized Controlled TrialEquivalence Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in RMD open, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02831855 (A PHASE 3B/4 RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED STUDY OF METHOTREXATE), which is not on this map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

NCT02831855 phase4completednot on this map

A phase 3b/4 randomized double blind placebo controlled study of methotrexate (mtx) withdrawal in subjects with rheumatoid arthritis (ra) treated with tofacitinib 11mg modified release (mr) formulation

TypeinterventionalSponsorPfizerRan2016 to 2018Enrolled694ConditionsRheumatoid ArthritisArmsCP-690,550, Methotrexate, Placebo
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Stanley B CohenMetroplex Clinical Research Center, Dallas, Texas, USA arthdoc@aol.com.
Janet PopeDepartment of Medicine, Division of Rheumatology, Western University, London, Ontario, Canada.ORCID 0000-0003-1479-5302
Boulos HaraouiCentre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
Eduardo MyslerOrganización Médica de Investigación, Buenos Aires, Argentina.
Annette DiehlPfizer Inc, Collegeville, Pennsylvania, USA.
Tatjana LukicPfizer Inc, New York, New York, USA.
Shixue LiuPfizer Inc, Shanghai, China.
Lori StockertPfizer Inc, Collegeville, Pennsylvania, USA.
Rebecca GerminoPfizer Inc, New York, New York, USA.
Sujatha MenonPfizer Inc, Groton, Connecticut, USA.
Harry ShiPfizer Inc, New York, New York, USA.
Edward C KeystoneDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo report the efficacy, safety and patient-reported outcome measures (PROs) of tofacitinib modified-release 11 mg once daily plus methotrexate in patients with rheumatoid arthritis (RA) from the open-label phase of Oral Rheumatoid Arthritis Trial (ORAL) Shift.

methodsORAL Shift was a global, 48-week, phase 3b/4 withdrawal study in patients with moderate to severe RA and an inadequate response to methotrexate. Patients received open-label tofacitinib modified-release 11 mg once daily plus methotrexate; those who achieved low disease activity (LDA; Clinical Disease Activity Index (CDAI)≤10) at week 24 were randomised to receive blinded tofacitinib 11 mg once daily plus placebo (ie, blinded methotrexate withdrawal) or continue with blinded tofacitinib 11 mg once daily plus methotrexate for another 24 weeks. Efficacy, PROs and safety from the open-label phase are reported descriptively.

resultsFollowing screening, 694 patients were enrolled and received tofacitinib plus methotrexate in the open-label phase. At week 24, 527 (84.5%) patients achieved CDAI-defined LDA. Improvements from baseline to weeks 12 and 24 were generally observed for all efficacy outcomes (including measures of disease activity, and response, LDA and remission rates) and PROs. Adverse events (AEs), serious AEs and discontinuations due to AEs were reported by 362 (52.2%), 20 (2.9%) and 41 (5.9%) patients, respectively. No deaths were reported.

conclusionsTofacitinib modified-release 11 mg once daily plus methotrexate conferred improvements in disease activity measures, functional outcomes and PROs, with most (84.5%) patients achieving CDAI-defined LDA after 24 weeks of open-label treatment; the safety profile was generally consistent with the historic safety profile of tofacitinib.Funded by Pfizer Inc; NCT02831855.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidAdultHumansMethotrexatePiperidinesPyrimidinesTreatment OutcomeAntirheumatic AgentsMethotrexatePiperidinesPyrimidinestofacitinibarthritisMethotrexatepatient reported outcome measuresrheumatoid

Identifiers

PMID34103405
PMCPMC8190053

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.