Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment

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Abstract

Background

This study evaluates patient-reported outcomes (PROs) in a double-blind, phase III study of baricitinib as monotherapy or combined with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) with no or minimal prior conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and naïve to biological DMARDs.

Methods

Patients were randomized 4:3:4 to MTX administered once weekly ( N = 210), baricitinib monotherapy (4 mg once daily (QD), N = 159), or combination of baricitinib (4 mg QD) and MTX (baricitinib + MTX, N = 215). PROs included the Patient’s Global Assessment of Disease Activity (PtGA), patient's assessment of pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration of morning joint stiffness (MJS), worst joint pain, worst tiredness, Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA), Short Form 36 version 2, Acute (SF-36); and EuroQol 5-Dimensions (EQ-5D) Health State Profile. Comparisons were assessed with analysis of covariance (ANCOVA) and logistic regression models.

Results

Compared to MTX, patients in both baricitinib groups reported greater improvement ( p ≤ 0.01) in HAQ-DI, PtGA, pain, fatigue, worst join pain, SF-36 physical component score, and EQ-5D at weeks 24 and 52. For the SF-36 mental component score, patients in both baricitinib groups reported statistically significant improvements ( p ≤ 0.01) at week 52 compared to MTX-treated patients. Statistically significant improvements ( p ≤ 0.05) were observed with the WPAI-RA for the baricitinib groups vs. MTX at week 24 and for the WPAI-RA daily activity and work productivity measures for baricitinib + MTX at week 52.

Conclusions

In this study, baricitinib alone or in combination with MTX, when used as initial therapy, resulted in significant improvement compared to MTX in the majority of the pre-specified PRO measures.

Trial Registration

ClinicalTrials.gov, NCT01711359. Registered on 18 October 2012.

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Most cited references 21

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The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.

Ferdinand C Breedveld, Michael Weisman, Arthur F Kavanaugh … (2006)

To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. This was a 2-year, multicenter, double-blind, active comparator-controlled study of 799 RA patients with active disease of < 3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P < or = 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.

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Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study

G T Jones, A Sebba, J Gu … (2009)

Background: The anti-interleukin (IL) 6 receptor antibody tocilizumab inhibits signalling of IL6, a key cytokine in rheumatoid arthritis (RA) pathogenesis. Objective: To evaluate through the AMBITION study the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA for whom previous treatment with methotrexate/biological agents had not failed. Methods: This 24-week, double-blind, double-dummy, parallel-group study, randomised 673 patients to either tocilizumab 8 mg/kg every 4 weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20 mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab 8 mg/kg. The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 24. Results: The intention-to-treat analysis demonstrated that tocilizumab was better than methotrexate treatment with a higher ACR20 response (69.9 vs 52.5%; p 3×–<5× upper limit of normal (1.0% vs 2.5%), respectively. Conclusion: Tocilizumab monotherapy is better than methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favourable benefit–risk, in patients for whom treatment with methotrexate or biological agents has not previously failed. Trial registration number: NCT00109408

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Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial.

Paul Emery, Ferdinand C Breedveld, Stephen D Hall … (2008)

Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis. The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis (COMET) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept. 542 outpatients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3-24 months were randomly assigned to receive either methotrexate alone titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints (DAS28) and radiographic non-progression measured with modified total Sharp score. Treatment was allocated with a computerised randomisation and enrolment system, which masked both participants and carers. Analysis was done by modified intention to treat with last observation carried forward for missing data. This study is registered with ClinicalTrials.gov, number NCT00195494). 274 participants were randomly assigned to receive combined treatment and 268 methotrexate alone. 132 of 265 (50%, 95% CI 44-56%) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 (28%, 23-33%) taking methotrexate alone (effect difference 22.05%, 95%CI 13.96-30.15%, p 5.1). 196 of 246 (80%, 75-85%) and 135 of 230 (59%, 53-65%), respectively, achieved radiographic non-progression (20.98%, 12.97-29.09%, p<0.0001). Serious adverse events were similar between groups. Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate. Wyeth Research.

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Author and article information

Contributors

Michael Schiff: 303-773-8429 , michael.schiff@me.com

Tsutomu Takeuchi: tsutake@z5.keio.jp

Roy Fleischmann: RFleischmann@arthdocs.com

Carol L. Gaich: gaich_carol_lynn@lilly.com

Amy M. DeLozier: delozier_amy@lilly.com

Douglas Schlichting: schlichting_douglas_e@lilly.com

Wen-Ling Kuo: kuo_wen_ling@lilly.com

Ji-Eon Won: won_ji_eon@lilly.com

Tara Carmack: carmack_tara@lilly.com

Terence Rooney: rooney_terence@lilly.com

Patrick Durez: patrick.durez@uclouvain.be

Saeed Shaikh: tsshaikh@bellnet.ca

Rodolfo Pardo Hidalgo: pardohidalgo@cersanjuan.com.ar

Ronald van Vollenhoven: Ronald.van.Vollenhoven@ki.se

Cristiano A. F. Zerbini: criszerb@uol.com.br

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 18 September 2017

Publication date PMC-release: 18 September 2017

Publication date (Print): 2017

Volume: 19

Electronic Location Identifier: 208

Affiliations

[1 ]ISNI 0000000107903411, GRID grid.241116.1, University of Colorado School of Medicine, ; Denver, CO 80045 USA

[2 ]ISNI 0000 0004 1936 9959, GRID grid.26091.3c, Keio University, ; Tokyo, Japan

[3 ]ISNI 0000 0000 9482 7121, GRID grid.267313.2, Metroplex Clinical Research Center, , University of Texas Southwestern Medical Center, ; Dallas, TX 75231 USA

[4 ]ISNI 0000 0000 2220 2544, GRID grid.417540.3, Eli Lilly and Company, ; Indianapolis, IN 46285 USA

[5 ]Eli Lilly and Company, Seoul, Republic of Korea

[6 ]ISNI 0000 0004 0461 6320, GRID grid.48769.34, Service et Pôle de Rhumatologie, , Cliniques Universitaires Saint-Luc, ; Brussels, Belgium

[7 ]ISNI 0000 0001 2294 713X, GRID grid.7942.8, Institut de Recherche Expérimentale et Clinique, , Université catholique de Louvain, Rheumatology, ; Brussels, Belgium

[8 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, McMaster University, ; Hamilton, ON Canada

[9 ]CER, San Juan, Argentina

[10 ]Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, The Netherlands

[11 ]Centro Paulista de Investigação Clinica, São Paulo, Brazil

Article

Publisher ID: 1410

DOI: 10.1186/s13075-017-1410-1

PMC ID: 5604362

PubMed ID: 28923098

SO-VID: 9d375b10-ec68-4869-845f-ea3969e6e454

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 5 January 2017

Date accepted : 25 August 2017

Funding

Funded by: Eli Lilly and Company and Incyte Corporation

Custom metadata

ScienceOpen disciplines: Orthopedics

Keywords: baricitinib,pro,jak inhibitor,ra,rheumatoid,tsdmard,health-related quality of life,health status indicators,haq-di

Data availability:

ScienceOpen disciplines: Orthopedics

Keywords: baricitinib, pro, jak inhibitor, ra, rheumatoid, tsdmard, health-related quality of life, health status indicators, haq-di

Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment

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Abstract

Background

Methods

Results

Conclusions

Trial Registration

Related collections

Orthopedics

Most cited references 21

The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.

Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study

Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial.

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