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

Rheumatoid Arthritis Clinical Trial

— RAILDTo  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05246293
• Other study ID #: C17-21
• Status: Recruiting
• Phase: Phase 2
• Start date: August 8, 2022
• Est. completion date: March 2, 2025

Study information

• Verified date: April 2022
• Source: National Institute of Respiratory Diseases, Mexico
• Contact: Jorge Rojas-Serrano, MD, PhD
• Phone: + 52 5554871700
• Email: jrojas[@]iner.gob.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Objectives

Primary objectives:

1. To evaluate the safety and tolerability of tofacitinib 5 mg PO BID as monotherapy for managing RA-ILD in RA-ILD patients.

2. 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.

3. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 2, 2025
• Est. primary completion date: March 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must fulfill ACR/EULAR 2010 RA classification criteria.

2. 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.

3. Patients must be 18 years of age or older.

4. There is no evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB).

5. 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.

6. 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:

1. Seropositivity for the following infections: HIV, HBV, and HCV.

2. Absolute neutrophil count = 1,200/L

3. Absolute platelet count = 100,000 /L

4. Severe renal damage with GFR < 30 ml/min based on CKD-EPI formula.

5. AST or ALT greater than 1.5 times the upper limit of normal AST and ALT levels

6. Severe hepatic, hematologic, gastrointestinal, cardiac, and neurological disease may put the patient´s life at risk regardless of ILD severity.

7. 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.

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Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial
• Rheumatoid Arthritis

Intervention

Drug:
• Tofacitinib
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

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas	Mexico City	Tlalpan

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Respiratory Diseases, Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (3)

Citera G, Mysler E, Madariaga H, Cardiel MH, Castaneda O, Fischer A, Richette P, Chartrand S, Park JK, Strengholt S, Rivas JL, Thorat AV, Girard T, Kwok K, Wang L, Ponce de Leon D. Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients: Post Hoc Analysis From 21 Clinical Trials. J Clin Rheumatol. 2021 Dec 1;27(8):e482-e490. doi: 10.1097/RHU.0000000000001552. — View Citation

Harigai M. Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis. Rheumatology (Oxford). 2019 Feb 1;58(Suppl 1):i34-i42. doi: 10.1093/rheumatology/key287. — View Citation

Vacchi C, Manfredi A, Cassone G, Cerri S, Della Casa G, Andrisani D, Salvarani C, Sebastiani M. Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Arthritis. Case Rep Med. 2021 Apr 22;2021:6652845. doi: 10.1155/2021/6652845. eCollection 2021. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	6 minutes walk test	walked metters in 6 minutes	52 weeks
Secondary	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
Secondary	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