Table 2.

Ongoing and unpublished randomized clinical trials with immunosuppressive agents in CTD-ILD.

Study/Phase Study Identifier	Patients (n) Duration (Weeks)	Criteria for Defining CTD, ILD and Severity/Progression	Use of Immunosuppressive Agents	Primary Outcome
PULMORA Effects of Tofacitinib vs. MTX on RA-ILD Phase 4 NCT04311567	n = 48 24 weeks	- CTD: diagnosis of seropositive RA within 24 months prior to inclusion - ILD: pulmonary abnormalities suggestive of RA-ILD -severity/progression:/	Previous treatment with DMARDs is not allowed. History of prednisone use is allowed but should have been discontinued two weeks before baseline visit.	Change in total interstitial disease score of pulmonary abnormalities by HRCT
APRIL AbatacePt in RA-ILD Phase 2 NCT03084419	28 weeks n = 30	- CTD: diagnosis of RA - ILD: ILD associated with RA with supportive findings on PFT and HRCT - Progression: a decrease in FVC >5% within 24 months prior to inclusion or progression of lung fibrosis on HRCT as reported by a chest radiologist.	Treatment with other immunosuppressive agents, e.g., MMF—unless this has been discontinued with an adequate washout period—is not allowed. A stable dose of MTX and hydroxychloroquine for at least six weeks prior to baseline visit is permitted. Treatment with >10 mg prednisolone daily within six weeks or rituximab within 24 weeks prior to baseline visit is not allowed.	Change in FVC
SCLEROCYCCYC in SSc-ILD Phase 3 NCT01570764	n = 40 52 weeks	- CTD-ILD: SSc-ILD - Progression: worsening of ILD on HRCT and worsening of FVC and/or TLC ≥10% and/or worsening of DLCO ≥ 15% as compared to values obtained within 3–18 months preceding inclusion	Treatment with CS >15 mg/d during the last three months, CYC during the last 12 months or rituximab during the last six months prior to inclusion is not allowed. Treatment with MTX or MMF at inclusion is not allowed.	Change in FVC
EvER-ILD Evaluation of Efficacy and Safety of Rituximab With MMF in Patients With ILD [105] Phase 3 NCT02990286	n = 122 26 weeks	- (CTD-)ILD: diagnosis of NSIP on histopathology or HRCT (basal predominant reticular abnormalities with traction bronchiectasis, peri-bronchovascular extension and subpleural sparing, frequently associated with ground-glass attenuation) and associated with differentiated CTD of IPAF or idiopathic ILD - Progression: patients who did not respond, relapsed or were not able to continue at least one first-line immunosuppressive treatment of ILD. The absence of response was defined as either a decrease or an increase, but < 10% in FVC%pred.	Treatment with immunosuppressive agents other than CS (AZA, CYC, MTX, cyclosporine, tacrolimus, leflunomide) within two weeks prior to inclusion or IVIG, hydroxychloroquine or other monoclonal antibody therapies within six months prior to inclusion are not allowed.	Change in FVC%pred
RECITALR ituximab Versus CYC in CTD-ILD [106] Phase2/3 NCT01862926	n = 116 48 weeks	- CTD-ILD: ILD associated with SSc, idiopathic interstitial myopathy and MCTD-severe and/or progressive ILD: intention of the caring physician to treat the ILD with IV CYC (deteriorating symptoms attributable to ILD, deteriorating PFTs, worsening gas exchange or extent of ILD) and when there is a reasonable expectation that immunosuppressive treatment will stabilize or improve CTD-ILD. In individuals with SSc, it is anticipated that subjects will fulfil the criteria for extensive disease defined by Goh et al.	Immunosuppressive therapy (other than CS) received within two weeks prior to inclusion is not allowed. Previous treatment with rituximab and/or intravenous CYC is not allowed.	Change in FVC
ATtackMy-ILD Abatacept in Myositis-associated ILD Phase 2 NCT03215927	n = 20 24 weeks	- CTD: diagnosis of anti-synthetase syndrome - ILD: reticulation, honeycombing or ground glass opacities (GGO) - Severe and/or progressive ILD (a) baseline FVC <80% or (b) FVC 80–100% with ≥10% decline in FVC in the last 12 months prior to inclusion	Inclusion criterium is the use of a stable dose of steroids, one of the other immunosuppressive agents (MMF or AZA) or a combination of steroid and an immunosuppressive agent. Other immunosuppressive agents, including MTX, cyclosporine, IVIG, tacrolimus, CYC or tofacitinib, are not allowed. Biologicals, i.e., rituximab, anti-TNF agents, tocilizumab, are not allowed.	Change in FVC%pred
CATR-PAT CYC and AZA vs. Tacrolimus in Anti-synthetase Syndrome-related ILD Phase 3 (open label) NCT03770663	n = 76 52 weeks	- CTD-ILD: ILD associated with anti-synthetase syndrome - Moderate to severe ILD: FVC <80% and/or DLCO <70%	Previous use of CYC, AZA or tacrolimus in the last six months prior to inclusion is not allowed. Previous use of three daily IV steroids <3 months before inclusion is not allowed. Patients with worsening or relapse under prednisone >0.5 mg/kg/day are excluded.	Progression-free survival
Basiliximab as a Treatment of Interstitial Pneumonia in Clinical Amyopathic Dermatomyositis Patients Phase 2NCT03192657	n = 100 52 weeks	- CTD-ILD + severity/progression: Dermatomyositis and interstitial pneumonia and meeting at least two of four criteria: (1) interstitial pneumonia images on HRCT, (2) DLCO ≤ 60%, (3) elevated serum KL-6, (4) elevated serum anti-MDA5 (+).	Previous application of immunosuppressive agents or any target treatment for dermatomyositis is not allowed.	Survival

ILD: interstitial lung disease; CTD-ILD: connective tissue disease-associated ILD; NSIP: non-specific interstitial pneumonia; IPAF: idiopathic pneumonia with autoimmune features; SSc-ILD: systemic sclerosis-associated interstitial lung disease; RA-ILD: rheumatoid arthritis-associated interstitial lung disease; MCTD: mixed connective tissue disease; CS: corticosteroids; MMF: mycophenolate mofetil; MTX: methotrexate; DMARD: disease modifying anti-rheumatic drugs; CYC cyclophosphamide; AZA: azathioprine; HRCT: high-resolution computed tomography; PFT: pulmonary function test; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide; TLC: total lung capacity; IV: intravenous; IVIG: intravenous immunoglobulin.