Evidence map›Paper›PMID 37351781›Full record

ArticleRheumatology and therapy2023

Pain and Inflammation as Mediators of Tofacitinib Treatment Effect on Fatigue in Patients with Ankylosing Spondylitis: A Mediation Analysis.

Lars Erik Kristensen, Victoria Navarro-Compán, Marina Magrey, Andrew G Bushmakin, Joseph C Cappelleri, Arne Yndestad, Oluwaseyi Dina, Peter C Taylor

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Rheumatology and therapy, 2023. 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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.5field-weighted citation impact, top 17% 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.

NCT01786668 phase2completednot on this map

A Phase 2, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study Of The Efficacy And Safety Of Tofacitinib In Subjects With Active Ankylosing Spondylitis (as)

TypeinterventionalSponsorPfizerRan2013 to 2015Enrolled208ConditionsAnkylosing SpondylitisArmsTofacitinib 2 mg, Tofacitinib 5 mg, Tofacitinib 10 mg, Placebo
NCT03502616 phase3completednot on this map

A phase 3, randomized, double-blind, placebo-controlled, study of the efficacy and safety of tofacitinib in subjects with active ankylosing spondylitis (as)

TypeinterventionalSponsorPfizerRan2018 to 2020Enrolled270ConditionsAnkylosing SpondylitisArmsTofacitinib
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. 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

8 authors at 4 institutions in 3 countries.

Lars Erik KristensenThe Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Victoria Navarro-CompánUniversity Hospital La Paz, IdiPaz, Madrid, Spain.
Marina MagreyDivision of Rheumatology, Case Western Reserve University, Cleveland, OH, USA.
Andrew G BushmakinPfizer Inc, Groton, CT, USA.
Joseph C CappelleriPfizer Inc, Groton, CT, USA.
Arne YndestadPfizer Inc, Oslo, Norway.
Oluwaseyi DinaPfizer Inc, 235 East 42nd Street, New York, NY, 10017, USA. Oluwaseyi.Dina@pfizer.com.
Peter C TaylorBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Pfizer (United States) · USCase Western Reserve University · USCopenhagen University Hospital · DKUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionTofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Using mediation modelling, we describe interrelationships between fatigue, pain, morning stiffness, C-reactive protein (CRP) and tofacitinib treatment in patients with AS.

methodsData from phase 2 (NCT01786668)/phase 3 (NCT03502616) studies of patients receiving tofacitinib 5 mg twice daily (BID) or placebo were used. Initial models included treatment as the independent binary variable (tofacitinib 5 mg BID versus placebo); fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F; model A] or Bath AS Disease Activity Index [BASDAI] Q1 [model B]) as the dependent variable; and pain (total back pain/nocturnal spinal pain [model A] or pain measured by BASDAI Q2/3 [model B]), morning stiffness (BASDAI Q5/6) and CRP as mediator variables.

resultsPooled data from 370/371 patients were included in models A/B. Initial models demonstrated that tofacitinib treatment affects fatigue mainly indirectly via pain and morning stiffness. As a result, initial models were respecified to exclude direct treatment effect and the indirect effect via CRP. For respecified model A, 44.0% of the indirect effect of tofacitinib treatment on fatigue was mediated via back pain/morning stiffness, 40.0% via morning stiffness alone and 16.0% via back pain alone (all P < 0.05). For respecified model B, 80.8% of the indirect effect of tofacitinib treatment on fatigue was mediated via pain/morning stiffness and 19.2% via pain alone (both P < 0.05).

conclusionsIn tofacitinib-treated patients with AS, improvements in fatigue were collectively mediated through combined treatment effects on morning stiffness and pain.

Indexed as

Ankylosing spondylitisC-reactive proteinMediation modellingMorning stiffnessPainTofacitinib

Identifiers

PMID37351781
PMCPMC10326212
OpenAlexW4381716200

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.