Evidence map›Paper›PMID 36076054›Full record

ArticleRheumatology and therapy2022

Identifying and Quantifying the Role of Inflammation in Pain Reduction for Patients With Psoriatic Arthritis Treated With Tofacitinib: A Mediation Analysis.

Kurt de Vlam, Philip J Mease, Andrew G Bushmakin, Roy Fleischmann, Alexis Ogdie, Valderilio F Azevedo, Joseph F Merola, John Woolcott, Joseph C Cappelleri, Lara Fallon and 1 more

2 registry-linked trialsOpen access · goldAbstract read
In one paragraph

Article in Rheumatology and therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.9field-weighted citation impact, top 26% 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.

NCT01877668 phase3completednot on this map

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of Tofacitinib (CP-690,550) Or Adalimumab In Subjects With Active Psoriatic Arthritis

TypeinterventionalSponsorPfizerRan2014 to 2015Enrolled422ConditionsPsoriatic ArthritisArmsTofacitinib 5 mg BID, Tofacitinib 10 mg BID, Adalimumab, Placebo
NCT01882439 phase3completednot on this map

A Phase 3, Randomized, Double-blind, Placebo-controlled Study Of The Efficacy And Safety Of 2 Doses Of Tofacitinib (Cp-690,550) In Subjects With Active Psoriatic Arthritis And An Inadequate Response To At Least One Tnf Inhibitor

TypeinterventionalSponsorPfizerRan2013 to 2016Enrolled395ConditionsPsoriatic ArthritisArmsTofacitinib, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  2. Review
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

11 authors at 9 institutions in 5 countries.

Kurt de VlamDepartment of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
Philip J MeaseSwedish Medical Center, University of Washington, Seattle, WA, USA.
Andrew G BushmakinPfizer Inc, Groton, CT, USA.
Roy FleischmannMetroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Alexis OgdiePerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Valderilio F AzevedoUniversidade Federal do Paraná, Curitiba, Brazil.
Joseph F MerolaDivision of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
John WoolcottPfizer Inc, Collegeville, PA, USA.
Joseph C CappelleriPfizer Inc, Groton, CT, USA.
Lara FallonPfizer Inc, Kirkland, Montreal, QC, Canada. lara.fallon@pfizer.com.
Peter C TaylorUniversity of Oxford, Oxford, UK.
Pfizer (United States) · USHarvard University · USKU Leuven · BEPfizer (Canada) · CASwedish Medical Center · USThe University of Texas Southwestern Medical Center · USUniversidade Federal do Paraná · BRUniversity of Oxford · GBUniversity of Pennsylvania · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionPain is a multidimensional factor and core domain of psoriatic arthritis (PsA). This analysis aimed to quantify the role of potential inflammation-associated outcomes on pain reduction in patients with PsA receiving tofacitinib, using mediation modeling.

methodsPooled data were from two phase 3 studies (OPAL Broaden and OPAL Beyond) of patients with active PsA treated with tofacitinib 5 mg twice daily or placebo. Mediation modeling was utilized to quantify the indirect effects (via Itch Severity Item [ISI], C-reactive protein [CRP] levels, swollen joint count [SJC], Psoriasis Area and Severity Index [PASI], and enthesitis [using Leeds Enthesitis Index]) and direct effects (representing all other factors) of tofacitinib treatment on pain improvement.

resultsThe initial model showed that tofacitinib treatment affects pain, primarily indirectly, via ISI, CRP, SJC, PASI, and enthesitis (overall 84.0%; P = 0.0009), with 16.0% (P = 0.5274) attributable to the direct effect. The model was respecified to exclude SJC and PASI. Analysis of the final model revealed that 29.5% (P = 0.0579) of tofacitinib treatment effect on pain was attributable to the direct effect, and 70.5% (P < 0.0001) was attributable to the indirect effect. ISI, CRP, and enthesitis mediated 37.4% (P = 0.0002), 15.3% (P = 0.0107), and 17.8% (P = 0.0157) of the tofacitinib treatment effect on pain, respectively.

conclusionsThe majority of the effect of tofacitinib on pain was collectively mediated by itch, CRP, and enthesitis, with itch being the primary mediator of treatment effect.

trial registrationNCT01877668, NCT01882439. GRAPHICAL PLS.

Indexed as

InflammationPainPsoriatic arthritisTofacitinib

Identifiers

PMID36076054
PMCPMC9510078
OpenAlexW4294970515

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.