Evidence map›Paper›PMID 26275429›Full record

Trial reportAnnals of the rheumatic diseases2016

Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs.

Christina Charles-Schoeman, Gerd Burmester, Peter Nash, Cristiano A F Zerbini, Koshika Soma, Kenneth Kwok, Thijs Hendrikx, Eustratios Bananis, Roy Fleischmann

Erratum issued 9 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 9 registered trials, which are not on this map. Cited by 35 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 2 pooled it
6.4field-weighted citation impact, top 3% of its field
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.

NCT00413660 phase2completednot on this map

A Phase 2B, Randomized, Double Blind, Placebo-Controlled, Multicenter Study To Compare 6 Dose Regimens Of CP-690,550 Vs. Placebo, Each Combined With Methotrexate, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis Who Have Had An Inadequate Response To Methotrexate Alone

TypeinterventionalSponsorPfizerRan2007 to 2008Enrolled509ConditionsArthritis, RheumatoidArmsCP-690,550, placebo
NCT00550446 phase2completednot on this map

A Phase 2b, Randomized, Double Blind, Placebo Controlled Active Comparator, Multicenter Study To Compare 5 Dose Regimens Of CP- 690,550 And Adalimumab Versus Placebo, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis

TypeinterventionalSponsorPfizerRan2007 to 2009Enrolled386ConditionsArthritis, RheumatoidArmsAdalimumab, CP-690-550, CP-690,550, Placebo
NCT00603512 phase2completednot on this map

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Confirm Dose Responsiveness Following 12 Weeks of the Administration of CP-690,550 (4 Doses) or Placebo in Subjects With Active Rheumatoid Arthritis Inadequately Controlled With Methotrexate Alone

TypeinterventionalSponsorPfizerRan2008 to 2008Enrolled140ConditionsArthritis, RheumatoidArmsPlacebo, CP-690,550
NCT00687193 phase2completednot on this map

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Confirm Dose Responsiveness Following 12 Weeks Of The Administration Of CP-690,550 (5 Doses) Or Placebo In Subjects With Active Rheumatoid Arthritis Inadequately Responding To At Least 1 DMARD

TypeinterventionalSponsorPfizerRan2009 to 2010Enrolled318ConditionsArthritis, RheumatoidArmsPlacebo, CP-690,550
NCT00814307 phase3completednot on this map

Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP-690,550 Monotherapy In Patients With Active Rheumatoid Arthritis

TypeinterventionalSponsorPfizerRan2009 to 2010Enrolled611ConditionsArthritis, RheumatoidArmsCP-690,550, Placebo
NCT00847613 phase3completednot on this map

Phase 3 Randomized, Double Blind, Placebo Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate

TypeinterventionalSponsorPfizerRan2009 to 2012Enrolled800ConditionsArthritis, RheumatoidArmsCP-690,550, Placebo
NCT00853385 phase3completednot on this map

Phase 3 Randomized, Double-Blind, Active Comparator, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate

TypeinterventionalSponsorPfizerRan2009 to 2011Enrolled717ConditionsRheumatoid ArthritisArmsCP 690,550, CP-690,550, Placebo, Biologic TNFi
NCT00856544 phase3completednot on this map

Phase 3, Randomized, Double Blind, Placebo Controlled Study Of The Safety And Efficacy Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background DMARDS

TypeinterventionalSponsorPfizerRan2009 to 2011Enrolled795ConditionsArthritis, RheumatoidArmsCP-690,550, Placebo
NCT00960440 phase3completednot on this map

Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Safety And Efficacy Of 2 Doses Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate With Inadequate Response To TNF Inhibitors

TypeinterventionalSponsorPfizerRan2009 to 2011Enrolled399ConditionsArthritis, RheumatoidArmsCP-690,550, Placebo
3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.

  1. Pooled it
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  13. Efficacy of Janus kinase inhibitors in rheumatoid arthritis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
  14. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 4 countries.

Christina Charles-SchoemanUniversity of California, Los Angeles, California, USA.
Gerd BurmesterCharité-University Medicine Berlin, Berlin, Germany.
Peter NashRheumatology Research Unit, Nambour Hospital, Sunshine Coast, Australia Department of Medicine, University of Queensland, Queensland, Australia.
Cristiano A F ZerbiniCentro Paulista de Investigação Clinica, São Paulo, Brazil.
Koshika SomaPfizer Inc, Groton, Connecticut, USA.
Kenneth KwokPfizer Inc, New York, New York, USA.
Thijs HendrikxPfizer Inc, Collegeville, Pennsylvania, USA.
Eustratios BananisPfizer Inc, Collegeville, Pennsylvania, USA.
Roy FleischmannDepartment of Medicine, Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Pfizer (United States) · USCentro Paulista de Investigação Clinica · BRCharité - Universitätsmedizin Berlin · DEMetroplex Clinical Research Center · USNambour General Hospital · AUUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesBiological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR).

methodsData were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed.

results2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs).

conclusionsTofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations. TRIAL REGISTRATION NUMBERS: (NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385).

Indexed as

AdultAntirheumatic AgentsArthritis, RheumatoidDrug-Related Side Effects and Adverse ReactionsDrug Therapy, CombinationFemaleHumansMaleMethotrexateMiddle AgedPiperidinesPyrimidinesPyrrolesTreatment OutcomeAntirheumatic AgentsMethotrexatePiperidinesPyrimidinesPyrrolestofacitinibAnti-TNFDMARDs (biologic)DMARDs (synthetic)Rheumatoid ArthritisTreatment

Identifiers

PMID26275429
PMCPMC4941182
OpenAlexW2128510662

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

and 3 more above

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.