Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease.

Study Overview
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Brief Summary
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Nowadays, no single drug is approved to treat rheumatoid arthritis-related interstitial lung disease (RA-ILD). The medical management of this clinical condition is empirical and controversial. There is preliminary data that tofacitinib may have a beneficial effect in treating RA-ILD. Tofacitinib may have a double role in treating RA-ILD: treat RA disease activity and an anti-fibrotic possible impact. Moreover, tofacitinib may be used as monotherapy for the treatment of rheumatoid arthritis (RA) This is a phase IIa clinical trial to evaluate the safety and tolerability of tofacitinib in RA-ILD patients.

Detailed Description
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This is a phase 2 open-label study designed to evaluate the safety and tolerability of tofacitinib in RA-ILD patients. Patients who met the inclusion criteria of the study protocol will receive tofacitinib 5 mg BID for 12 months. Objectives Primary objectives: To evaluate the safety and tolerability of tofacitinib 5 mg PO BID as monotherapy for managing RA-ILD in RA-ILD patients. To evaluate the pulmonary function of patients treated with tofacitinib PO BID as monotherapy to manage RA-ILD in RA-ILD patients, at baseline, at three months of follow-up, at six months of follow-up, and one year of follow-up. To estimate the efficacy of tofacitinib 5 mg PO BID as monotherapy for the management of RA-ILD, in RA-ILD patients, at three months of follow-up, at six months of follow-up, and at one year of follow-up, according to the ACR 20, 50, 70 response criteria, and the following disease activity scores index: DAS 28, CDAI and SDAI. All the included patients will receive Tofacitinib in doses of 5 mg BID until the end of the protocol.

Official Title
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Safety and Tolerability of Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease (RAILDTo Trial).

Conditions
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Rheumatoid Arthritis, Interstitial Lung Disease

Intervention / Treatment
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* Drug: Tofacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must fulfill ACR/EULAR 2010 RA classification criteria. Patients must have an interstitial lung disease confirmed by a high-resolution computed tomography scan or a surgical lung biopsy. Nonspecific interstitial pneumonia, usual interstitial pneumonia, lymphocytic pneumonia, and organized pneumonia, either by HRCT or surgical biopsy, will be included. Patients must be 18 years of age or older. There is no evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB). Patients must discontinue using the non-permitted medications: leflunomide, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, and any biologic disease-modifying drug (bDMDARDs) such as anti-TNF therapy, rituximab, tocilizumab, etc. Patients must have a stable prednisone dose of ≤ 10 mg/ PO/day for at least three months. All patients must have stable doses of prednisone during the last three months of follow-up, and the prednisone dose must be ≤ 10 mg/day. Patients without a prednisone history in the previous three months may also be included in the protocol. Exclusion Criteria: Seropositivity for the following infections: HIV, HBV, and HCV. Absolute neutrophil count ≤ 1,200/L Absolute platelet count ≤ 100,000 /L Severe renal damage with GFR < 30 ml/min based on CKD-EPI formula. AST or ALT greater than 1.5 times the upper limit of normal AST and ALT levels Severe hepatic, hematologic, gastrointestinal, cardiac, and neurological disease may put the patient´s life at risk regardless of ILD severity. Severe active infections at baseline evaluation, such as pneumonia, urinary tract infections, meningitis. 8 History of drug abuse or alcoholism. 9. History of any malignancy 10. Patients with an FVC < 40% of what is expected will be excluded from the study. -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a phase 2 open-label study designed to evaluate the safety and tolerability of tofacitinib in RA-ILD patients. Patients who met the inclusion criteria of the study protocol will receive tofacitinib 5 mg BID for 12 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tofacitinib Arm<br>Tofacitinib in doses of 5 mg BID, in RA-ILD patients at stable doses of prednisone ≤ 10 mg/day during the last three months. | Drug: Tofacitinib<br>* Tofacitinib in doses of 5 mg BID, in RA-ILD patients at stable doses of prednisone ≤ 10 mg/day during the last three months. Patients who met the inclusion criteria of the study protocol will received tofacitinib 5 mg BID for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events | Adverse event: Any untoward medical occurrence in a subject being included in the trial, in which the event may not necessarily have a causal relationship with the treatment. Examples of adverse events are as follows: abnormal test findings, clinically significant symptoms and signs, hypersensitivity reactions, and progression or worsening of RA or RA-ILD. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Vital Capacity (liters) | Forced vital capacity (FVC) on spirometry, the data will be presented as percentages of predicted values, according to sex, age, height, and weight. | 52 weeks | 
| Carbon monoxide diffusing capacity (DLCO) (mil/min/mmHg) | The data will be presented as percentages of predicted values, according to sex, age, height, and weight. | 52 weeks | 
| 6 minutes walk test | walked metters in 6 minutes | 52 weeks | 
| Rheumatoid arthritis disease activity according to the simplified disease activity (SDAI) index. | The SDAI index consists of the algebraic sum of the following items: tender joint count, swollen joint count, c-reactive protein, rheumatoid arthritis activity according to the patient, disease activity according to the attending physician. | 52 weeks | 
| Rheumatoid arthritis disease activity according to the Disease Activity Score Index (DAS28) | The DAS28 score is calculated with the tender joint count, swollen joint count, eritrosedimentation rate, patients' global health assesment aacording with the following formula DAS28 = ( 0.56 * sqr(TJC)) + (0.28 * sqr(SJC)) + ( 0.7 * ln(VSG)) + (0.014 * GH) | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Interstitial Lung Disease, Usual interstitial pneumonia, Tofacitinib, Rheumatoid Arthritis-related interstitial lung disease