Myasthenia Gravis (MG) is an autoimmune disorder mediated by autoantibodies targeting the acetylcholine receptor (AChR) at the neuromuscular junction, characterized by skeletal muscle weakness and fatigability (1, 2). The core pathological mechanism involves antibody-mediated blockade of neuromuscular signal transmission. The annual incidence of MG is estimated at 8–10 per million person-years, with a global prevalence of approximately 150–250 per million (3). While corticosteroids and azathioprine remain foundational immunosuppressants in myasthenia gravis (MG) management, their broad immunomodulatory mechanisms contribute to dose-limiting toxicities and cumulative organ damage in chronic use (4).

Building upon an enhanced understanding of MG pathogenesis, novel immunotherapeutic strategies are continuously emerging. Novel biologic agents now offer targeted alternatives: B-cell depletion therapies (anti-CD20 rituximab and anti-CD19 inebilizumab), FcRn antagonists (efgartigimod/rozanolixizumab), and complement inhibitors (eculizumab/ravulizumab) have demonstrated clinical efficacy with distinct safety profiles (5, 6). However, current B-cell-depleting agents still face challenges related to therapeutic fluctuations and long-term safety profiles (7, 8).

Telitacicept is a novel recombinant fusion protein that ameliorates symptoms by simultaneously blocking two key ligands regulating B-cell development—B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL). This dual inhibition suppresses aberrant B-cell differentiation and pathogenic autoantibody production, especially antibodies targeting AChR (9). This agent has demonstrated efficacy in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and received FDA orphan drug designation for MG treatment in 2022 (10–12).

Preliminary results from a randomized controlled trial (RCT) investigating telitacicept for MG indicated favorable efficacy and safety (13). However, given the substantial heterogeneity inherent in MG, the strictly controlled RCT data require further validation of its effectiveness and safety profile in environments more closely mirroring clinical practice. Real-world studies (RWS) are uniquely positioned to provide comprehensive evidence complementary to RCTs (14).

Therefore, this study aims to analyze the clinical utility of telitacicept in a series of 17 MG patients based on real-world data (RWD), assessing its impact on symptom alleviation, quality of life (QoL) improvement, and safety. This research will provide clinical evidence for the role of telitacicept within the MG therapeutic armamentarium and serve as an important complement to prior RCT findings.

In this real-world investigation of patients with myasthenia gravis (MG), telitacicept demonstrated significant clinical efficacy and a favorable safety profile. A key methodological strength underpinning these conclusions is the application of a Bayesian analytical framework. This approach was deliberately chosen to enhance statistical power and mitigate the inherent limitations of a small sample size, a common challenge in real-world evidence generation (19). By formally integrating robust prior evidence from registrational trials with our contemporary data, the Bayesian model yields more precise and credible efficacy estimates (20, 21). To formally integrate prior knowledge, we established a conservative Beta (10,8) prior distribution based on historical data where the response rate was 56.25%. Upon updating with our compelling observed data—wherein 12 of 15 patients (80.00%) met the primary composite endpoint—the model yielded a posterior mean response rate of 66.67% with a 95% credible interval of [49.99, 81.43%]. Crucially, this translates into a 97.49% posterior probability that the true response rate exceeds the clinically significant 50% threshold, and a 79.54% probability of it exceeding 60%. This probabilistic conclusion offers a more nuanced and clinically informative alternative to conventional frequentist analysis. Furthermore, sensitivity analyses confirmed that these efficacy estimates remained robust across various prior specifications, bolstering the reliability of our findings (22). Notably, since 37% of patients in the historical placebo cohort had thymoma (vs. 0% in our cohort), we rigorously addressed this heterogeneity through Bayesian sensitivity analyses. When replacing the historical-data prior with a non-informative prior (Beta (1,1)) and a skeptical prior (centered at θ < 0.3 with equivalent sample size), the posterior probability of an efficacy rate exceeding 50% remained consistently high (>90% in all scenarios, Figure 3). This demonstrates that the conclusions are robust across different prior assumptions. Per FDA Bayesian guidance (23, 24), such insensitivity to prior specification confirms that our findings are predominantly driven by the observed study data rather than external sources. Clinical interpretations should therefore prioritize the current trial’s evidence. Therefore, the substantial symptomatic improvements observed in our cohort are supported by a rigorous and intentionally chosen analytical strategy.

Efficacy assessments revealed significant improvements in myasthenic symptoms. The substantial decline in MG-ADL scores (mean reduction: 3.8 points from baseline 8.0 ± 4.4 to 4.2 ± 3.1) demonstrated telitacicept’s capacity to alleviate functional impairment in daily activities. This reduction exceeded the minimum clinically important difference (MCID) threshold (≥2 points), effectively transitioning patients from “mild functional limitation” (MG-ADL > 5) to “near-normal daily living” (MG-ADL < 5). The objective clinical response rate (80.0% achieving ≥5-point QMG reduction—meeting guideline-defined moderate improvement) closely approached outcomes from registrational Phase II trials (92.9% at 160 mg; 100% at 240 mg achieving ≥3-point QMG reduction), underscoring telitacicept’s applicability despite the heightened complexity of our cohort (45% post-thymectomy; 70.6% requiring multi-drug immunosuppressive regimens). And our core efficacy data demonstrate that telitacicept broadly improves function across multiple muscle groups, with the most pronounced improvement observed in limb and bulbar muscles. This finding is consistent with the comprehensive enhancement in patients’ daily living activities (as measured by the MG-ADL score) and the significant steroid-sparing effect.

Critically, glucocorticoid burden markedly decreased during telitacicept therapy. The mean daily prednisone dosage declined by 76.0% (10.41 ± 7.30 mg to 2.50 ± 3.21 mg), with three patients achieving sustained zero-dose maintenance. This steroid-sparing effect carries profound implications: It mitigates exposure to endocrine-related comorbidities such as osteoporosis (prednisone >7.5 mg/day increases fracture risk by 2-fold) while enhancing treatment adherence and quality of life. Telitacicept’s metabolic safety advantages over conventional immunosuppressants (e.g., tacrolimus-associated hyperglycemia and nephrotoxicity) further position it as an optimal complement to glucocorticoid minimization strategies (25, 26). Reduced dependence on traditional agents may benefit patients with treatment-refractory profiles (27).

Notably, the profound clinical amelioration observed in our MuSK antibody-positive patient (MG-ADL: 9 → 3; QMG: 17 → 8) provides critical mechanistic insights into managing this distinct serotype. Unlike AChR-MG, MuSK-MG is characterized by IgG4 autoantibodies which exert pathogenicity by blocking MuSK-LRP4 interaction independent of complement activation, thereby rendering C5 inhibitors ineffective. Furthermore, recent evidence suggests MuSK-MG is predominantly driven by high-turnover short-lived plasmablasts rather than long-lived plasma cells (9, 28). The observed efficacy likely stems from telitacicept’s dual BLyS/APRIL blockade: by suppressing nascent plasma cell generation and depriving cells of APRIL—a critical survival factor—it accelerates the apoptosis of these short-lived IgG4-secreting plasmablasts inherent to MuSK-MG. This upstream suppression directly halts pathogenic antibody production, bypassing the irrelevant complement pathway and providing a precise therapeutic rationale for this often-refractory subtype (29–31).

Interindividual efficacy variation observed in our cohort, potentially modulated by disease chronicity and immunophenotypic factors, necessitates personalized therapeutic strategies. Dose escalation to 240 mg achieved minimal symptom expression in 2/4 patients, further suggesting the value of protocol individualization (18).

Safety outcomes aligned with telitacicept’s established autoimmune disease profile. All adverse events were mild-to-moderate and manageable without intervention (32). Telitacicept demonstrated a stable and favorable safety profile in this short-term real-world cohort (33, 34) with no severe infections, hypogammaglobulinemia, or autoimmune exacerbations observed. One discontinuation (transient gastric intolerance, possibly mediated via APRIL intestinal signaling) and one self-limiting injection-site reaction were the only tolerability concerns. Vigilance remains warranted regarding latent infection reactivation in high-risk patients (one case involved historical syphilis with preserved serostatus), emphasizing the need for pretreament screening and monitoring.

Emerging molecular therapies delineate distinct management strategies focusing on either rapid rescue or sustained disease modification. FcRn and complement inhibitors are characterized by a rapid onset of action suitable for managing myasthenic crisis by targeting downstream effectors or circulating IgG (35). Conversely, telitacicept targets the upstream survival of plasma cells to address the fundamental source of autoimmunity. This mechanism supports long-term disease stabilization and deep corticosteroid tapering as evidenced by the 76% dose reduction in our cohort. Furthermore, telitacicept offers durable remission without the pulsatile fluctuations or antibody rebound risks associated with cyclic FcRn inhibitor regimens (36). Consequently, telitacicept occupies a critical therapeutic niche as a broad-spectrum and steroid-sparing maintenance agent.

Although our findings are encouraging, several limitations warrant cautious interpretation. Firstly, the retrospective nature of the study carries the potential for selection bias; consequently, prospective studies are required to validate the generalizability of our conclusions (37). Secondly, the current follow-up duration was insufficient to evaluate long-term patterns of relapse, evolution of drug resistance, and sustainability of corticosteroid taper during extended therapy. Thirdly, the limited sample size (n = 15) and inadequate representation of crucial patient subgroups—such as those with ocular myasthenia gravis (MG), elderly patients (>65 years), and a sufficient number of MuSK antibody-positive (MuSK-Ab+) cases (only one was included)—restrict exploration of population heterogeneity. It should also be noted that the current study was limited by its small sample size and relatively short follow-up period (maximum 24 weeks), particularly for assessing rare but serious adverse events (SAEs) such as severe infections and hypogammaglobulinemia. Finally, the lack of systematic monitoring of target biomarkers (e.g., antibody titers, B-cell subset dynamics) limits inferences regarding the drug’s precise mechanisms of action. Future multi-center studies with expanded cohorts are urgently needed to strengthen the evidence base.

Collectively, by employing rigorous Bayesian methodology, this real-world study validates the clinical efficacy and safety of telitacicept in patients with MG, providing a more robust foundation for its broader clinical application. Future research should prioritize exploring personalized treatment strategies and accumulating long-term follow-up data. Efforts should focus on refining subtyping to identify optimal treatment candidates (e.g., thymoma-associated MG) and optimizing combination approaches (e.g., sequential use with FcRn inhibitors) to further enhance MG management.

This Bayesian real-world analysis confirms that telitacicept exhibits a high probability of clinical efficacy in AChR antibody-positive myasthenia gravis (MG) patients (posterior probability of response >50%: 0.9749%) alongside a favorable safety profile. The agent significantly improves daily living function and MG-specific symptom burden in the majority of treated patients, achieves clinically meaningful steroid-sparing effects, and demonstrates mild and manageable adverse events.