A 2023 review describes the use of intravenous immunoglobulin (IVIG) for the treatment of various idiopathic inflammatory myopathies (IIM), including interstitial lung disease (ILD). Evidence from several case reports and a retrospective review suggests that IVIG can improve outcomes in refractory patients with anti-synthetase syndrome (anti-SS)-associated ILD, a type of myositis-associated ILD. In the retrospective review, 7 of 17 patients (41%) achieved a forced vital capacity increase of >10% (see Table 1). [1]
Additionally, patients with anti-melanoma-differentiation-associated-gene-5 (MDA5) dermatomyositis associated with rapidly progressive ILD (RP-ILD) may benefit from a combined regimen of immunosuppressive therapy and IVIG, according to a retrospective study in China (see Table 2). This study reported a lower 6-month mortality rate compared to non-IVIG groups (23% vs 53%), suggesting that incorporating IVIG as first-line adjunct therapy may improve survival and remission, as well as reduce proxy markers of disease activity such as ferritin concentration, anti-MDA5 titer, and ground-glass opacity score. Based on these findings, the review authors recommend considering IVIG as a potential adjuvant treatment for patients with IIM-associated ILD, particularly those with MDA5 autoantibodies, RP-ILD, or a high early disease burden. [1]
A 2016 review described the off-label use of IVIG for refractory cases of ILD if patients fail to respond to standard immunosuppression. Despite the increased cost of IVIG, its use may confer less systemic toxicity, global immunosuppression, and risk of infection compared to traditional treatments. Based on data available at the time, the benefit of IVIG for ILD was extrapolated from its mechanism of action and use for various other inflammatory and autoimmune conditions, as well as anecdotal evidence and case series finding efficacy in ILD. In cases of severe myositis, which is associated with a high incidence of pulmonary involvement, findings from case reports, case series, and retrospective studies have observed a favorable response to IVIG therapy for outcomes related to muscle strength, creatine kinase levels, and skin lesions; randomized trials have also observed efficacy of IVIG for improvement of rash, muscle strength, and neurological symptoms in steroid-resistant myositis. Still, although myositis appears to overlap with ILD, data are less clear to indicate the role of IVIG for pathological mechanisms associated with concurrent pulmonary disease in cases of ILD. [2]
Due to IVIG use in ILD being based on anecdotal evidence, establishing causation is challenging without the ability to control for confounding variables, additional treatments, and patient-specific factors. In the cited case reports, dosing regimens of IVIG utilized include 2 g/kg monthly x 3 months for a case of severe polymyositis-associated ILD and 0.4 g/kg/day x 5 days for rapidly progressive ILD associated with either polymyositis or amyopathic dermatomyositis. Current use of IVIG, at the time this article was published, was noted to still be experimental and inconclusive, without evidence to support a well-defined dose. [2]
A 2023 systematic review and meta-analysis investigated the treatment of rapidly progressing ILD in adult patients with DM/polymyositis (PM), including treatments and outcomes. A total of 18 studies were included, comprising 6,058 patients and encompassing various treatment options, including IVIG. The combined prevalence of ILD within DM/PM populations was found to be 8.9%. Remission was achieved in 58.4% of patients (95% confidence interval [CI] 47.3% to 69.4%); treatment with biologic agents (including rituximab, tofacitinib, and tocilizumab) conferred the highest remission rate (74.7%, 95% CI 62.8% to 85.7%), followed by triple therapy (51.5%, 95% CI 27.6% to 75.4%), and combination disease-modifying antirheumatic drug (cDMARDs; 47.7%, 95% CI 24.8% to 70.6%). Use of IVIG was consolidated within triple therapy, which was defined as the addition of a third intravenous medication, including cyclophosphamide and immunoglobulin. Similarly, survival rates at 6 months were also highest with biologic agents (92.1%), followed by cDMARDs (82.8%), plasma exchange (55.8%), and then triple therapy (40.9%). Survival at 1 year was highest with biologics, followed by cDMARDs, then triple therapy (90.7%, 78.7%, and 66.0%, respectively). While biologic agents demonstrated the greatest efficacy for treatment of rapidly progressing ILD in this patient population, the true efficacy of IVIG is difficult to ascertain, as results were combined with other triple therapy options. [3]
Additional review articles specific to the management of myositis-associated ILD similarly highlight the use of IVIG as adjunctive therapy. Although most evidence for IVIG in inflammatory myositis focuses on skin and muscle involvement, case reports and retrospective studies indicate potential benefits for pulmonary disease, particularly in patients with refractory ILD despite standard immunosuppressive therapy. In these studies, roughly 40% of patients achieved a ≥10% improvement in forced vital capacity, often with substantial reductions in glucocorticoid doses. IVIG is generally well tolerated, though rare serious adverse events, including renal impairment, thrombosis, hemolytic anemia, and transfusion-related acute lung injury, have been reported. Given these observations, IVIG may be considered a salvage or adjunctive option in patients with refractory myositis-associated ILD, providing a potential therapeutic benefit when conventional treatments are insufficient. [4], [5], [6]