Effects of Tofacitinib vs Methotrexate on Rheumatoid Arthritis Interstitial Lung Disease (PULMORA)

  • STATUS
    Recruiting
  • End date
    Nov 30, 2024
  • participants needed
    48
  • sponsor
    Vastra Gotaland Region
Updated on 10 May 2022
methotrexate
prednisone
tofacitinib
DMARD
interstitial lung disease
antirheumatics

Summary

Pulmonary abnormalities are present in up to 60% of patients with early rheumatoid arthritis (RA), and up to 10% of the patients will develop clinical interstitial lung disease (ILD). Recent data indicate that inhibition of Janus kinase is beneficial for this extra-articular manifestation. Our goal is to determine whether tofacitinib is an effective and safe treatment, compared to standard-of-care methotrexate, for subclinical and clinical ILD in patients with early RA. The study also explores disease mechanisms in lungs and joints, to identify potential biomarkers for diagnosis, prognosis, and response to treatment of RA-ILD.

Description

Study objectives:

Primary objective: Effects of tofacitinib compared to that of methotrexate on interstitial pulmonary abnormalities at 24 weeks.

Secondary objectives: Effects of tofacitinib compared to that of methotrexate on pulmonary abnormalities and function, RA disease activity and remission rates and patient reported outcome measures at different time points. Frequency of adverse events.

Exploratory objectives: Effects of tofacitinib compared to that of methotrexate on cellular and molecular activity profiles of clinical samples from joints and lungs.

Study design:

A randomized, actively controlled, open-label, assessor-blinded, multicenter 48 weeks phase IV trial. The study design includes an optional sub-study collecting tissue samples using ultrasound-guided synovial biopsies, bronchoalveolar lavage and Particles in Exhaled Air (PExA).

Study population and intervention:

Patients with early untreated RA with active and seropositive disease will be eligible for screening and the performance of high-resolution computed tomography (HRCT). Subjects with pulmonary abnormalities suggestive of RA-ILD will be randomized (1:1) to tofacitinib 5 mg BID (group 1) or standard-of-care methotrexate 20 mg weekly (group 2) for 48 weeks. All patients receive prednisone with tapering for 6 weeks. Patients with incomplete response at 24 weeks will escalate to combination therapy with tofacitinib+methotrexate (group 3). Intra-articular injections of cortisone will be allowed during the study.

145 subjects will be included and screened (part 1), and approximately 48 subjects will be randomized to active treatment (part 2).

Details
Condition Rheumatoid Arthritis, Interstitial Lung Disease Due to Systemic Disease (Disorder), RA, ILD
Treatment methotrexate, tofacitinib
Clinical Study IdentifierNCT04311567
SponsorVastra Gotaland Region
Last Modified on10 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

The subject has given written consent to participate in the study
Diagnosis of seropositive (i.e., presence of RF and/or anti-CCP antibodies) rheumatoid arthritis (RA) according to the ACR/EULAR 2010 criteria within 24 months
No previous treatment with disease modifying anti-rheumatic drugs (DMARDs). History of prednisone use is allowed but should have been discontinued 2 weeks before baseline measurement
Active disease with ≥2 painful and ≥2 swollen joints in 66/68 joints and CRP ≥2.0 mg/L
Aged 18-80 years

Exclusion Criteria

Current active inflammatory joint disease other than RA
Significant and/or uncontrolled cardiac, pulmonary disease, nervous system, renal, hepatic, endocrine or gastrointestinal disorders or severe RA which in the investigator's opinion would preclude patient participation
Malignancy within the past 5 years, except for successfully treated cervical carcinoma in situ, basal cell and squamous cell carcinoma of the skin, with no evidence of recurrence or metastatic disease for at least 3 years
Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection
Active infection (excluding fungal infections of nail beds) requiring i.v. anti-infectives within 4 weeks, or oral anti-infectives within 2 weeks prior to baseline
For subjects in part II the following exclusion criteria also apply
Women of childbearing potential not willing or able to use highly effective methods of birth control per ICH M3 (R2) for 28 days prior and 3 months after end of study
Pregnant or lactating women
Positive tests for hepatitis B (HBsAg or HBV DNA),hepatitis C serology or SARS-CoV2
History of herpes zoster infection during last 10 years
History or risk of venous thromboembolism or diverticulitis
Positive tuberculosis history and/or positive Quantiferon test
Hemoglobin <90 g/L
Absolute neutrophil count < 1500 cells/uL
ASAT or ALAT >2.0 times the upper limit of normal
High or very high risk (≥ 5%) of cardiovascular death within 10 years by SCOREx1,5
Multiple incidental solid/subsolid lung nodules of size ≥6 mm, single incidental solid lung nodules ≥8 mm
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