Evidence map›Paper›PMID 41294296›Full record

ArticleACR open rheumatology2025

Combining Pirfenidone With Mycophenolate Mofetil for Systemic Sclerosis-Related Interstitial Lung Disease (Scleroderma Lung Study III): An Investigator-Initiated, Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Dinesh Khanna, Cathie Spino, Donald P Tashkin, Elana J Bernstein, Jonathan Goldin, Eric C Kleerup, Airi Harui, Grace Ibrahim, Grace Hyun J Kim, Suiyuan Huang and 23 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACR open rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Combination antifibrotic and immunosuppressive therapy in progressive fibrosing ILD.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2026
    Article
  3. 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

33 authors.

Dinesh KhannaUniversity of Michigan, Ann Arbor.ORCID https://orcid.org/0000-0003-1412-4453
Cathie SpinoUniversity of Michigan, Ann Arbor.
Donald P TashkinDavid Geffen School of Medicine, University of California at Los Angeles.
Elana J BernsteinColumbia University Irving Medical Center, New York, New York.
Jonathan GoldinDavid Geffen School of Medicine, University of California at Los Angeles.
Eric C KleerupDavid Geffen School of Medicine, University of California at Los Angeles.
Airi HaruiDavid Geffen School of Medicine, University of California at Los Angeles.
Grace IbrahimDavid Geffen School of Medicine, University of California at Los Angeles.
Grace Hyun J KimDavid Geffen School of Medicine, University of California at Los Angeles.ORCID https://orcid.org/0000-0003-1225-3489
Suiyuan HuangUniversity of Michigan, Ann Arbor.
Richard McLainUniversity of Michigan, Ann Arbor.
Yi-Hsuan TuUniversity of Michigan, Ann Arbor.
Vivek NagarajaUniversity of Michigan, Ann Arbor, and Mayo Clinic Arizona, Scottsdale.ORCID https://orcid.org/0000-0002-4930-3200
Richard M SilverMedical University of South Carolina, Charleston.ORCID https://orcid.org/0000-0002-2038-3278
Virginia D SteenGeorgetown University Medical Center, Washington, DC.
S Samuel WeigtDavid Geffen School of Medicine, University of California at Los Angeles.
Joyce S LeeUniversity of Colorado, Aurora.
Aryeh FischerUniversity of Colorado, Aurora, and Eli Lilly and Company, Indianapolis, Indiana.
Mary Beth ScholandUniversity of Utah, Salt Lake City.
Jessica K GordonHospital for Special Surgery, New York, New York.ORCID https://orcid.org/0000-0001-8068-0592
Paul F DellaripaBrigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.ORCID https://orcid.org/0000-0003-0237-739X
Ivan O RosasBrigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Gary M HunninghakeBrigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Marcin A TrojanowskiChobanian & Avedisian School of Medicine, Boston University, Boston, Massachusetts.
Robert W SimmsChobanian & Avedisian School of Medicine, Boston University, Boston, Massachusetts.
Jane E DematteFeinberg School of Medicine, Northwestern University, Chicago, Illinois.
Vivien M HsuRutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey.
Robyn T DomsicUniversity of Pittsburgh, Pittsburgh, Pennsylvania.ORCID https://orcid.org/0000-0002-2765-0922
Ganesh RaghuUniversity of Washington, Seattle.
Maureen D MayesMcGovern Medical School, University of Texas Health Houston.ORCID https://orcid.org/0000-0001-5070-2535
Ryan D BoenteIndiana University School of Medicine, Indianapolis.ORCID https://orcid.org/0000-0003-3750-1311
Michael D RothDavid Geffen School of Medicine, University of California at Los Angeles.ORCID https://orcid.org/0000-0003-2194-6578
Scleroderma Lung Study III Investigators

Funding

Genentech
6 · The paper itself

Abstract

objectiveMycophenolate mofetil (MMF) can stabilize or improve lung function in systemic sclerosis-related interstitial lung disease (SSc-ILD). We hypothesized that combining MMF with pirfenidone (PFD) would produce a significantly more rapid and/or greater improvement in lung function.

methodsA randomized (1:1), double-blind, placebo (PLA)-controlled phase 2 trial was conducted in SSc-ILD in which patients received PFD or PLA (801 mg three times daily) along with MMF (1,500 mg twice daily) for 18 months. The primary outcome was change in percent predicted forced vital capacity (FVC-%). Linear mixed-effects models assessed treatment differences in a modified intention-to-treat population.

resultsOnly fifty-one of 150 intended subjects (34%) were randomized (MMF+PLA, n = 24; MMF+PFD, n = 27). The FVC-% improved from baseline to 18 months by 2.24 ± 1.35 (least-squares mean [LSM] ± SEM) in the MMF+PLA group and 2.09 ± 1.28 in the MMF+PFD group (LSM treatment difference -0.14; P = 0.93). Median time to achieve a ≥3% improvement in FVC-% was numerically faster in the MMF+PFD versus MMF+PLA group (12.3 vs 17.8 months, respectively), but the difference was not significant (P = 0.33). For secondary outcomes, only the change over 18 months in the Patient-Reported Outcomes Measurement Information System 29-item physical function score, favoring MMF+PFD, reached statistical significance (P = 0.04). Although other related patient-reported outcomes (PROs) numerically favored the MMF+PFD group, as did quantitative high-resolution computed tomography measures of ILD, the differences between groups did not reach statistical significance. Early withdrawals from study medication and adverse events of special interest were numerically greater with MMF+PFD (n = 8 vs 2 and n = 20 vs 7, respectively).

conclusionIn this underpowered study, there was no statistically significant treatment difference in overall change in FVC-% between groups. MMF+PFD was not as well tolerated as MMF+PLA.

Identifiers

PMID41294296
PMCPMC12648624

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Registered trials

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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.