Efficacy and safety of pharmacological treatments for autoimmune disease-associated interstitial lung disease: A systematic review and network meta-analysis.

BACKGROUND: Immunosuppressants, biologic agents, antifibrotic drugs, and other drugs can be used to treat autoimmune disease-associated interstitial lung disease (ILD), but the preferred treatment is uncertain. We aimed to evaluate the efficacy and safety of multiple drugs in the treatment of autoimmune disease-associated ILD. METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to July 2023. Primary outcomes were percentage of predicted forced vital capacity (FVC% predicted) and discontinuations for adverse events (AEs). We estimated summary mean differences (MDs) and odds ratios (ORs) using network meta-analysis with fixed effects. RESULTS: The analysis is based on 15 RCTs involving 1832 patients. In terms of FVC% predicted, mycophenolate mofetil (MMF) (MD 1.27, 95 % credible interval [CrI] 0.08 to 2.43), cyclophosphamide (1.89, 0.10 to 3.68), rituximab (9.29, 2.79 to 15.80), tocilizumab (6.30, 3.27 to 9.34), nintedanib (1.71, 0.54 to 2.88), pirfenidone (2.03, 0.65 to 3.40) and nintedanib+MMF (2.43, 0.95 to 3.89) were more effective than placebo. Analysis based on a small sample size showed that riociguat also had good therapeutic potential when compared with placebo. By contrast, bosentan and pomalidomide showed no significant difference compared with placebo. Regarding discontinuations for AEs, nintedanib (OR 2.09, 95 %CrI 1.20 to 3.73) and pirfenidone (3.46, 1.31 to 10.56) were associated with higher dropout rates than placebo, and the combination therapy of nintedanib+MMF did not increase the risk of AEs compared with nintedanib monotherapy. CONCLUSIONS: MMF, cyclophosphamide, rituximab, tocilizumab, nintedanib and pirfenidone are effective in the treatment of autoimmune disease-associated ILD. The efficacy of riociguat and the superiority of combination therapy need to be demonstrated in more RCTs. The tolerance of nintedanib and pirfenidone is a concern, but most of their AEs are mild and controllable.

Clinical Characteristics of Dermatomyositis with Interstitial Lung Disease: A Retrospective Case-Control Study.

INTRODUCTION: Interstitial lung disease (ILD) is a common complication of dermatomyositis (DM) and one of the main risk factors for poor prognosis in DM patients. The aim of this study was to reveal the clinical characteristics of DM patients with ILD. METHODS: Clinical data from the Second Affiliated Hospital of Soochow University were used to conduct a retrospective case-control study. Univariate and multivariate logistic regression analysis were performed to identify risk factors for ILD in DM. RESULTS: A total of 78 DM patients were included in this study, including 38 DM patients with ILD and 40 DM patients without ILD. Compared with patients without ILD, patients with ILD were older (59.6 vs. 51.2 years, P = 0.004), and had higher rates of clinically amyopathic DM (CADM) (45 vs. 20%, P = 0.019), Gottron's papules (76 vs. 53%, P = 0.028), mechanic's hands (13 vs. 0%, P = 0.018), myocardial involvement (29 vs. 8%, P = 0.014), and higher positive rates of anti-SSA/Ro52 (74 vs. 20%, P < 0.001) and anti-melanoma differentiation-associated gene-5 (MDA5) (24 vs. 8%, P = 0.048) antibodies, while albumin (ALB) (34.5 vs. 38.0 g/l, P = 0.006), prognostic nutritional index (PNI) (40.3 vs. 44.7, P = 0.013), the rates of muscle weakness (45 vs. 73%, P = 0.013) and heliotrope rash (50 vs. 80%, P = 0.005) were lower. In addition, the five patients who died were all DM patients with ILD (13 vs. 0%, P = 0.018). Multivariate logistic regression showed that old age (odds ratio [OR] = 1.119, 95% confidence interval [CI] = 1.028-1.217, P = 0.009), Gottron's papules (OR = 8.302, 95% CI = 1.275-54.064, P = 0.027) and anti-SSA/Ro52 (OR = 24.320, 95% CI = 4.102-144.204, P < 0.001) were independent risk factors for ILD in DM. CONCLUSIONS: DM patients with ILD usually present with older age, higher rates of CADM, Gottron's papules, mechanic's hands, myocardial involvement, higher positive rates of anti-MDA5 and anti-SSA/Ro52 antibodies, lower ALB, PNI, and lower rates of muscle weakness and heliotrope rash. Old age, Gottron's papules, and anti-SSA/Ro52 were independent risk factors for ILD in DM.

Comparative efficacy and safety of Janus kinase inhibitors and biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and network meta-analysis.

OBJECTIVE: To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD). METHODS: PubMed, Embase, Cochrane library and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to April 2020. The active drugs included three JAK inhibitors and eight bDMARDs while the control drugs included placebo or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Outcomes include American College of Rheumatology 20% response (ACR20), Disease Activity Score in 28 joints (DAS28), Health Assessment Questionnaire-Disability Index (HAQ-DI) and discontinuations for adverse events (AEs). We estimated summary odds ratios (ORs) and weighted mean differences (WMDs) using network meta-analysis with random effects. RESULTS: Eighty-eight RCTs with 31,566 patients were included. All JAK inhibitors and bDMARDs were more effective than placebo in ACR20 (ORs ranging between 3.05 and 5.61), DAS28 (WMDs ranging between -1.91 and -0.80) and HAQ-DI (WMDs ranging between -0.34 and -0.21). Tocilizumab, certolizumab pegol and upadacitinib showed relatively good efficacy in these three outcomes according to their relative ranking. Notably, tocilizumab was more effective than other active drugs in DAS28 (WMDs ranging between -1.11 and -0.49). Compared with the lower recommended doses, increasing the doses of JAK inhibitors (baricitinib 4 mg versus 2 mg, tofacitinib 10 mg versus 5 mg and upadacitinib 30 mg versus 15 mg) cannot provide significant additional benefits. In terms of discontinuations for AEs, all active drugs showed no significant difference compared with placebo except certolizumab pegol [OR 1.65, 95% credible interval (CrI) 1.06-2.61] and rituximab (3.17, 1.11-10.80). CONCLUSIONS: Tocilizumab, certolizumab pegol and upadacitinib may have relatively good efficacy in patients with RA after treatment failure with csDMARDs. RA patients taking a JAK inhibitor may have a preference for a lower recommended dose.

Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: In recent years, an increasing number of drugs have been proved to be associated with the induction of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This article reviews the latest research progress on drug-induced AAV. DATA SOURCES: We conducted a comprehensive and detailed search of the PubMed database. The search terms mainly included drug-induced, ANCA, and vasculitis. STUDY SELECTION: We summarized the original articles and reviews on drug-induced AAV in recent years. The extracted information included the definition, epidemiology, associated drugs, pathogenesis, clinical features, diagnosis, treatment, and prognosis of drug-induced AAV. We also focused on the differences between drug-induced AAV and primary vasculitis. RESULTS: The offending drugs leading to drug-induced AAV are almost from pharmacologic categories and we need to be vigilant when using these drugs. The pathogenesis of drug-induced AAV might be multifactorial. The formation of neutrophil extracellular traps is an important mechanism for the development of drug-induced AAV. The clinical features of drug-induced AAV are similar to those of primary AAV. Understanding the difference between drug-induced AAV and primary AAV is helpful to identify drug-induced AAV. Stopping the offending drug at once after diagnosis may be sufficient for those patients with mild symptoms. Immunosuppressive therapy should only be used in patients with vital organs involvement. CONCLUSIONS: Patients with drug-induced AAV usually have a good prognosis if they stop using the offending drug immediately. Recent advances in research on AAV are expected to help us better understand the pathogenesis of drug-induced AAV.