Rheumatoid Arthritis Associated Interstitial Lung Disease
Conditions
Keywords
randomized controlled trial, Tocilizumab, rituximab
Brief summary
This is a 52-week, multicenter, prospective, open-label, randomized controlled clinical study, comparing the efficacy and safety of tocilizumab, rituximab, and csDMARD methotrexate in patients with RA-ILD.
Detailed description
This is a multicenter, randomized, controlled clinical trial designed to evaluate the efficacy and safety of tocilizumab and rituximab in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). A total of 204 eligible participants will be enrolled from 20 centers across China and randomly assigned in a 1:1:1 ratio to one of three treatment arms: (1) tocilizumab in combination with conventional disease-modifying antirheumatic drugs (cDMARDs); (2) rituximab in combination with cDMARDs; or (3) methotrexate added to the participant's pre-existing background immunosuppressive regimen. Each treatment arm will include 68 participants. Participants will be assessed at baseline and at Weeks 4, 12, 24, and 52 following treatment initiation. Efficacy and safety data will be collected throughout the study to evaluate treatment response and tolerability. Safety assessments will include the incidence of adverse events (AEs), serious adverse events (SAEs), treatment discontinuations due to AEs or SAEs, and other clinically relevant safety outcomes.
Interventions
DRUGTocilizumab
Tocilizumab will be administered intravenously at a dose of 8 mg/kg every 4 weeks in addition to stable background csDMARD therapy maintained throughout the study period.
DRUGRituximab (RTX)
Rituximab will be administered intravenously at a dose of 1,000 mg on Day 0, 1,000 mg at Week 2, 500 mg at Week 26, and 500 mg at Week 52, in addition to stable background csDMARD therapy maintained throughout the study period.
DRUGMethotrexate
Methotrexate will be administered orally at a dose of 15 mg once weekly in addition to stable background csDMARD therapy
Sponsors
Chinese SLE Treatment And Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Fulfillment of the 2010 ACR/EULAR classification criteria for RA. * HRCT findings consistent with interstitial lung disease (ILD), including ground-glass opacities, reticular abnormalities, fibrotic linear opacities, traction bronchiectasis, or other compatible features, with pulmonary infection, cardiogenic pulmonary edema, and alveolar hemorrhage excluded. The extent of ILD involvement must be ≥20% on HRCT, as assessed by central review. * Pulmonary function impairment defined as forced vital capacity (FVC) \<80% of predicted and/or diffusing capacity of the lung for carbon monoxide (DLCO) \<70% of predicted. * Participants receiving glucocorticoids prior to enrollment must be on a stable dose of prednisone ≤10 mg/day (or equivalent) for at least 4 weeks before baseline. * Participants receiving a csDMARD prior to enrollment must be on a stable regimen for at least 4 weeks before baseline. * Able and willing to provide written informed consent and comply with study requirements, including scheduled visits and follow-up assessments.
Exclusion criteria
* Presence of other autoimmune diseases. * Presence of severe, uncontrolled clinically significant organ dysfunction or other medical conditions that, in the investigator's judgment, would place the participant at unacceptable risk. * History of malignancy within 5 years prior to screening. * Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study period. * Known hypersensitivity to tocilizumab, telitacicept, methotrexate, or any of their excipients. * Active hepatitis B or C virus infection, active tuberculosis, active herpes zoster infection, or a history of serious infection within 12 weeks prior to study treatment initiation (defined as an infection requiring hospitalization or intravenous antimicrobial therapy). * Severe hypoalbuminemia or serum immunoglobulin G (IgG) level \<6 g/L. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 × the upper limit of normal (ULN), total bilirubin \>1.5 × ULN, or creatinine clearance (CrCl) \<60 mL/min. * Participation in another interventional clinical trial within 4 weeks prior to screening. * Inability to adequately perform pulmonary function testing or other study-related assessments. * Any other condition that, in the opinion of the investigator, would make the participant unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in FVC from baseline to week 52 | week 52±2 | Change in Forced Vital Capacity (FVC) from Baseline to Week 52 (±2 Weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Experiencing a Composite Clinical Endpoint | Up to Week 52 (±2 Weeks) | Composite clinical endpoint defined as the occurrence of at least one of the following events: all-cause mortality, hospitalization for any cause, hospitalization due to progression of respiratory disease, or death due to progression of respiratory disease. |
| Change in mMRC Dyspnea Scale Score from Baseline | Baseline to Week 52 (±2 Weeks) | Change in Modified Medical Research Council (mMRC) Dyspnea Scale Score from Baseline to Week 52 (±2). The mMRC Dyspnea Scale is scored from 0 to 4, with higher scores indicating more severe dyspnea. |
| Change in DLCO from Baseline | Baseline to Week 52 (±2 Weeks) | Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) from Baseline. |
| Change in DLCO % Predicted from Baseline | Baseline to Week 52 (±2 Weeks) | Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO % Predicted) from Baseline |
| Change in Chest HRCT Score from Baseline | Baseline to Week 52 (±2 Weeks) | Change in the total chest high-resolution computed tomography (HRCT) score, inflammatory activity score, and fibrosis score. |
| Change in FVC % Predicted from Baseline | Baseline to Week 52 (±2) | Change in Percent Predicted Forced Vital Capacity (FVC % Predicted) from baseline to week 52 (±2). |
Countries
China
Contacts
CONTACTXinping Tian
CONTACTShangyi Jin
PRINCIPAL_INVESTIGATORXinping Tian
Peking Union Medical College Hospital
Outcome results
None listed