Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune diseases primarily involving skeletal muscles of the limbs and the skin (Lundberg et al., 2017). The clinical manifestations of IIMs are diverse and highly heterogeneous. They can be classified into several subtypes, including dermatomyositis (DM), antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), polymyositis (PM), and sporadic inclusion body myositis (sIBM); of them, DM, ASS, and IMNM are the most prevalent (Lundberg et al., 2017; Tanboon and Nishino, 2019).

Interstitial lung disease (ILD) is the most prevalent complication associated with IIMs and the leading cause of hospitalization and mortality in patients with IIMs. Based on the onset pattern of ILD, ILD can be categorized into acute/subacute and chronic types. Patients with acute/subacute ILD exhibit a lower survival rate than those with chronic ILD (Fujisawa, 2021; Vu et al., 2023).

Thus far, no standard treatment has been recommended for IIM-associated ILD (IIM-ILD). Research on supporting optimal treatment options for IIM-ILD has been limited; most relevant studies have used a retrospective nonrandomized observational or case series design. Treatment approaches primarily include glucocorticoids (GCs), immunosuppressants [e.g., cyclophosphamide (CTX), mycophenolate mofetil (MMF), calcineurin inhibitors (CNIs), and azathioprine], rituximab (RTX), tofacitinib, and plasma exchange (Fujisawa, 2021; Thong et al., 2023). In this study, we assessed the outcomes of telitacicept treatment in 10 IIM-ILD cases. Our results may offer a novel therapeutic option for IIM-ILD management.

Among the 10 patients included in this study, four were male and six were female; their ages ranged from 45 to 75 years. Of them, seven patients had ASS-associated ILD, one had anti-MDA5 antibody-positive DM-associated ILD, and two had DM-associated ILD. Table 1 presents the baseline data of all patients.

Of all patients, one experienced hoarseness, difficulty drinking water, and choking, in addition to involvement of the skin, muscles, joints, and lungs. Four patients with severe ILD and PaO2/FiO2 ratio <300 were treated with GCs and RTX, followed by telitacicept. Six patients with a poor response to conventional immunosuppressants were classified as having refractory IIM-ILD. Of them, two patients received treatment with RTX combined with telitacicept, whereas four were treated only with telitacicept because they had an increased risk of infection.

During treatment, all patients were monitored for 24 weeks. Over the course of this treatment, prednisone acetate dosage was gradually reduced to 5–7.5 mg/day, whereas that of telitacicept was increased to 160 mg every 2 weeks. No patient experienced muscle pain, weakness, rash, or joint pain, and all reported considerable relief from dyspnea. Laboratory indicators, including CK, LDH, ALT, AST, ferritin, ESR, and CRP, returned to normal levels (Table 1). The PaO2/FiO2 ratio improved by 28.2% compared with baseline (Figure 1A), whereas the 6MWT outcomes improved by 34% (Figure 1C). In all patients with muscle involvement, the MMT-8 score increased by 25.1% (Figure 1B). All patients’ chest HRCT scans revealed varying degrees of reduction in bilateral lung lesions (Figure 2), and lung function demonstrated considerable improvements (Figure 3); in particular, compared with baseline, FVC% and DLCO% increased by 20.4% and 30.2%, respectively (Figure 4). Only one patient received additional treatment with nintedanib for pulmonary fibrosis due to insufficient improvement in lung function.

Regarding adverse events, one patient experienced a mild lung infection; nevertheless, no further infection occurred after telitacicept dosage was reduced. Two patients experienced pruritus at the injection site, lasting for 1–2 days, which resolved spontaneously. None of the patients exhibited leukopenia, gastrointestinal disorders, or neurological diseases; moreover, they demonstrated minimal IgG-related adverse reactions during treatment, indicating good safety.

The current recommendations for IIM-ILD treatment have been primarily based on empirical research; moreover, definitive guidelines for the optimal treatment of IIM-ILD remain unavailable. Recommendations suggest that treatment decisions should be tailored to a patient’s specific form of ILD and myositis antibody profile (Fujisawa, 2021). For patients with acute and subacute ILD, including those with anti-MDA5 antibody-positive DM and ASS, high-dose GCs should be combined with CNIs (Fujisawa, 2021; Fujisawa et al., 2021; Chen et al., 2022). A triple therapy regimen comprising GCs, CNIs, and CTX may be administered to patients with rapid ILD progression and multiple adverse prognostic factors (Tsuji et al., 2020; Fujisawa, 2021). For patients with refractory ILD, options such as RTX, plasma exchange, and tofacitinib may be considered. Additionally, intravenous immunoglobulin has the functions of regulating immune cell activity, neutralizing autoantibodies, and downregulating chemotactic cytokines. Therefore, for patients with recurrent or refractory IIMs-ILD, intravenous immunoglobulin therapy can be administered (Gandiga et al., 2023). For those with chronic ILD, GCs and immunosuppressants, including CTX, azathioprine, MMF, and CNIs, may be administered (Mecoli and Christopher-Stine, 2018; Fujisawa, 2021; Moda et al., 2025).

IIM-ILD pathogenesis remains unclear. Nevertheless, in locally inflamed tissue of patients with DM, B-cell infiltration occurs around blood vessels and the muscle endometrium (Saketkoo et al., 2010). Moreover, JO-1 antibodies have recently been isolated from the alveolar lavage fluid of patients with IIM-ILD (Galindo-Feria et al., 2020). Activated B cells differentiate into plasma cells, which produce various antibodies such as antisynthetase and MDA5 antibodies; these antibodies bind to lung autoantigens and trigger tissue damage (Moda et al., 2025). Furthermore, studies have reported that follicular dendritic, T, and B cells contribute to the formation of inducible bronchus-associated lymphoid tissue (iBALT) at pulmonary interstitial lesion sites. iBALT exhibits germinal center activity, facilitating the induction of plasma cells that produce high-affinity antibodies, release neutrophil extracellular traps, and contribute to pulmonary fibrosis development (Akiyama and Kaneko, 2022). These findings indicate that B cells and plasma cells may be pivotal in IIM-ILD pathogenesis.

RTX, a chimeric CD20 monoclonal antibody, targets B cells and induces B-cell depletion; it is thus used in salvage treatment for refractory ILD (Reff et al., 1994; Ogawa et al., 2017; Liossis and Bounia, 2022). RTX exhibits substantial efficacy in patients with refractory ASS-ILD, severe ASS-ILD, recurrent or progressive ASS-ILD, and clinically amyopathic DM characterized by rapidly progressive (RP) ILD, as well as in patients with MDA5 antibody-positive DM-ILD (Allenbach et al., 2015; Doyle et al., 2018; So et al., 2018; Ge et al., 2021). However, RTX treatment can increase B-lymphocyte stimulator (BLyS) levels, possibly promoting reemergence of autoreactive B cells and contributing to disease recurrence over time (Cambridge et al., 2008; Ehrenstein and Wing, 2016).

BLyS, a type II membrane-bound protein from the tumor necrosis factor family, is mainly secreted by monocytes and macrophages (Mockel et al., 2021). BLyS is essential for B-cell survival, maturation, and class-switching, as well as plasma cell survival (Vincent et al., 2013). It also plays a major role in the pathogeneses of various autoimmune diseases. Patients with DM exhibiting elevated BLyS levels have an increased ILD risk (Matsushita et al., 2019). Furthermore, serum BLyS levels are correlated with ILD severity (Hamada et al., 2015). Notably, serum BLyS levels are positively associated with rapidly progressive ILD (RP-ILD) occurrence in patients with MDA5-positive DM (Shi et al., 2024). Therefore, BLyS may be strongly associated with IIM-ILD pathogenesis.

Telitacicept is a novel recombinant fusion protein, comprising the ligand-binding domain of the TACI receptor and the Fc segment of human IgG. It can effectively bind to and inhibit BLyS and proliferation-inducing ligand (APRIL) activities, thereby suppressing the development and survival of plasma cells and mature B cells (Dhillon, 2021; Shi et al., 2021; Fan et al., 2022). This drug has recently demonstrated favorable clinical efficacy and safety in Sjögren’s syndrome (Xu et al., 2024), systemic lupus erythematosus (SLE) (Jin et al., 2023; Wu et al., 2024), and rheumatoid arthritis (RA) (Dhillon, 2021). However, its therapeutic effect on IIM-ILD has not been reported thus far.

A combination of RTX and telitacicept can effectively neutralize elevations in BLyS levels, thereby delaying B-cell reactivation, improving remission rates, and reducing recurrence rates in patients with refractory lupus nephritis (Chen et al., 2025a; 2025b). Furthermore, sequential treatment with RTX and telitacicept can significantly reduce recurrence rates in patients with refractory anti-NMDA receptor encephalitis and MOG-associated demyelination (Zhang et al., 2025). However, the therapeutic effects of this combination in IIM-ILD have not yet been reported.

In the current study, we included 10 IIM-ILD cases; of them, four, who were newly diagnosed as having severe ILD, were treated with a combination of RTX and telitacicept. Six patients exhibited refractory IIM-ILD. Of them, four were treated with telitacicept because they had a high risk of infection associated with RTX; the remaining two patients were administered a combination of RTX and telitacicept. All 10 patients demonstrated symptom relief and considerable improvements in laboratory and imaging indicators, thereby providing the dual treatment effects for idiopathic inflammatory IIM-ILD. Telitacicept demonstrated favorable clinical efficacy and safety in our patients with anti-MDA5 antibody-positive DM-associated ILD and ASS-ILD.

Our results indicated that telitacicept can be used as a novel therapeutic for IIM-ILD treatment. However, because we did not include a control group, our results and conclusions may be constrained. Future studies should employ a prospective, controlled design to further validate the efficacy of telitacicept, both alone and in combination with RTX, in managing IIM-ILD. In addition, further extensive multicenter clinical studies are necessary to confirm the safety and efficacy of telitacicept in patients with connective tissue diseases and interstitial lung lesions, such as Sjögren’s syndrome, systemic sclerosis, and antineutrophil cytoplasmic antibody–associated vasculitis.