Case Series: Effectiveness and Safety of Telitacicept in Chinese Patients With Primary Sjögren's Disease

Telitacicept is a novel fusion protein developed specifically for treating B cell-mediated autoimmune diseases. Limited data are available on the use of telitacicept in patients with primary Sjögren's disease (pSjD). This case series evaluated the effectiveness and safety of telitacicept in seven female patients with pSjD, suggesting it may be a promising therapeutic option. pSjD is a complex chronic inflammatory autoimmune disease, often presenting clinically with dry mouth and dry eyes due to impaired salivary and lacrimal gland functions, respectively [1]. The pathogenesis of pSjD is intricate, characterized by chronic inflammatory cell infiltration [2]. A key feature of pSjD is the excessive activation of B cells mediated by T cells. B cells are involved in various aspects of pSjD pathogenesis, including the production of autoantibodies, antigen presentation, and cytokine production [3]. Critical players in B cell survival and activation, as well as in the prolonged lifespan of plasma cells, include B cell-activating factor (BAFF/BLyS) and a proliferation-inducing ligand (APRIL), which are produced by a range of innate immune cells [4]. Previous studies have reported elevated serum and saliva levels of BAFF/BLyS and APRIL in pSjD patients, which correlate with disease activity [5-7]. Telitacicept, a recombinant fusion protein, inhibits the maturation of immature B cells by blocking BLyS and prevents mature B cell differentiation into plasma cells by blocking APRIL, thereby reducing the secretion of autoantibodies [8]. In March 2021, telitacicept received its first approval in China for the treatment of patients with active systemic lupus erythematosus (SLE), based on its significant improvement in disease activity and acceptable safety profile in a phase IIb clinical trial [9]. Both SLE and pSjD are B cell-mediated autoimmune diseases characterized by high levels of autoantibodies [10]. The confirmed efficacy of telitacicept in SLE has further driven its expanded application in pSjD. Recently, a phase II clinical trial of telitacicept for pSjD showed promising clinical benefits and a favorable safety profile [11]. A multicenter phase III clinical trial of telitacicept is ongoing in China (NCT05673993). To date, there is limited data on the use of telitacicept in patients with pSjD, both in China and globally [11]. In this case series, the effectiveness and safety of telitacicept were assessed in seven patients with pSjD, whose baseline characteristics and treatment regimens differed from those in clinical trials. Notably, our study included patients with varying disease activity (European League Against Rheumatism Sjögren's Syndrome Disease Activity Index [ESSDAI] scores below 5 in some cases) and allowed continued use of corticosteroids and immunosuppressants, whereas clinical trials typically excluded such patients and required drug washout periods [11]. These differences provide valuable insights into the potential of telitacicept as a therapeutic option for pSjD in real-world clinical settings. This retrospective case series included patients diagnosed with pSjD at the Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, between March 2021 and December 2023. Eligible patients were aged 18 to 65 years and met the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for pSjD. All the included patients tested positive for anti-Sjögren's-syndrome-related antigen A (anti-SSA) antibodies and had been followed up for at least 8 weeks after initiating treatment with telitacicept. Exclusion criteria were use of other biological agents such as rituximab, belimumab, etanercept, or infliximab within 6 months prior to the administration of telitacicept; failure to complete at least one follow-up examination at our institution. The case series adhered to the principles outlined in the Declaration of Helsinki and received approval from the Medical Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (approve no. 2024–0077). As a retrospective study, the requirement for informed consent was waived by the Ethics Committee. All patients received telitacicept in combination with standard treatment regimens [12, 13], including glucocorticoids and/or immunosuppressants such as mycophenolate mofetil (MMF), hydroxychloroquine (HCQ), iguratimod (IGU), and cyclosporine (CsA). Telitacicept treatment was selected through a shared decision-making process between the physician and the patient. Telitacicept was administered subcutaneously at a dose of 80 mg or 160 mg, either once a week or every two weeks. Data were collected in patients with pSjD before and after treatment with telitacicept. Recorded variables included demographic information, concurrent use of immunosuppressants or glucocorticoids, and a range of laboratory tests such as total T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, natural killer (NK) cells, IgE, IgG, IgA, IgM, complement component 3 (C3), and complement component 4 (C4). Peripheral blood samples were collected in patients for the analysis of lymphocyte subset percentages. These subsets were detected by flow cytometry. Disease activity was assessed using the ESSDAI, a 12-domain clinician-reported outcome (ClinRO) instrument evaluating systemic disease activity, and the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), a 3-item patient-reported outcome (PRO) instrument measuring the severity of dryness, fatigue, and joint/muscle pain over the past 2 weeks. Both ESSDAI and ESSPRI scores were recorded at baseline and the last follow-up. In addition, patients achieving minimal clinically important improvement (MCII), defined as an ESSDAI score improvement of at least three points and an ESSPRI score decrease of at least one point or 15%, were counted. Seven cases were ultimately included in the current analysis. All seven patients were female, with ages ranging from 24 to 60 years and disease durations varying from 2 months to 7 years. Before the initiation of telitacicept treatment, all patients had been managed with glucocorticoids and/or immunosuppressants, including MMF, HCQ, IGU, and CsA. Specifically, two patients received combination therapy involving two immunosuppressants (IGU + CsA and HCQ + CsA, respectively), while the remaining five were administered monotherapy with a single immunosuppressant (MMF, HCQ, or IGU) (Table 1). After treatment with telitacicept, six of the seven patients had decreased ESSDAI scores and achieved MCII, while one patient showed an increase in ESSDAI score compared to baseline. All patients exhibited decreased their ESSPRI scores and achieved MCII (Figure 1). Furthermore, glucocorticoid doses could be reduced in all patients, with three cases having their doses reduced to 5 mg or lower (Table S1). Immunological biomarkers were assessed in six of the seven patients before and after telitacicept treatment. Among these six patients, reductions were observed in IgG, IgA, and IgM levels compared to baseline. C3 levels were increased in three patients and decreased in the remaining three. In terms of C4 levels, four patients experienced an increase, while two had a decrease (Table 1 and Figure 1). Case 6 underwent closer monitoring of lymphocyte subset percentages during telitacicept treatment. The patient exhibited a gradual increase in the proportion of CD8+ T cells, while the proportion of CD19+ B cells progressively decreased. In addition, the levels of NK cells showed an upward trend (Figure 1). Immunological testing was performed for five patients following telitacicept treatment. Regarding antinuclear antibody (ANA) titers, two patients experienced a decrease, from 1:3200 to 1:320 in case 4 and from 1:1000 to 1:100 in case 6. Meanwhile, one patient (case 4) showed an increase in the ANA titer, from 1:320 to 1:3200; the remaining patients exhibited no significant changes. Both patients who tested positive for RF showed a marked decrease in the RF titer after using telitacicept, from 49.6 IU/mL to 27.8 IU/mL in case 2 and from 43.3 IU/mL to 14.5 IU/mL in case 5 (Table 1). During the telitacicept treatment period, no serious adverse events were reported in the seven patients. To our knowledge, this is the first case series of pSjD patients treated with telitacicept, summarizing the characteristics and treatment outcomes of seven female patients administered telitacicept. The results demonstrated clinical improvements, with six patients showing decreased ESSDAI scores and all patients exhibiting reduced ESSPRI scores. These improvements were accompanied by reductions in glucocorticoid doses and stable immunosuppressant use. Immunologically, reductions in IgG, IgA, and IgM levels, along with specific changes in lymphocyte subsets observed in six patients, indicated immunomodulatory effects for telitacicept. Importantly, no serious adverse events were reported. These findings support the potential of telitacicept as an effective and safe treatment option for pSjD. In a phase II clinical trial of pSjD, telitacicept administered subcutaneously at 160 mg once a week significantly reduced the ESSDAI score at week 24 compared with placebo, as well as serum IgM, IgG, and IgA levels. In addition, patients reported significant improvement in fatigue symptoms, as assessed by the Multidimensional Fatigue Inventory [11]. These findings are consistent with improved disease activity, patient-reported outcomes, and immunological markers in this case series. Due to their condition, patients in this case series received telitacicept along with glucocorticoids ± immunosuppressants, which differs from the trial. Notably, glucocorticoid doses could be reduced in all patients, maintaining or reducing the doses of immunosuppressants. This is particularly significant considering the 2019 EULAR recommendations to minimize long-term glucocorticoid use in pSjD patients due to the risks of osteoporosis, hyperglycemia, and infections [12]. The ability to taper glucocorticoid use without compromising disease control underscores the potential therapeutic advantage of telitacicept. In addition, case 6, who underwent regular laboratory tests, showed a gradual increase in the proportion of CD8+ T cells and a decrease in CD19+ B cells during treatment, providing detailed insights into the immunomodulatory effects of telitacicept. This finding is in line with the known mechanism of action of telitacicept and corroborates clinical trials involving patients with SLE or pSjD [11, 14]. The therapeutic landscape for pSjD has seen the exploration of several BAFF/BLyS and APRIL-targeted drugs, among which telitacicept, belimumab, and ianalumab are prominent. Belimumab, an anti-BAFF/BLyS monoclonal antibody, is already approved for treating active SLE and lupus nephritis (LN) [15, 16]. The open-label phase II BELISS study demonstrated that belimumab significantly decreased ESSDAI scores at week 28 and reduced serum immunoglobulin and RF levels in patients with SjD [17]. Another phase II study of belimumab combined with rituximab indicated that this combination therapy led to a consistent and significant improvement in ESSDAI scores, accompanied by a sustained reduction in peripheral CD19+ B cells [18]. Ianalumab, a monoclonal antibody targeting the BAFF receptor, exhibited a dose-related reduction in disease activity in patients with pSjD at week 24, as evidenced by ESSDAI scores [19]. Comparatively, the present case series on telitacicept, which targets both BAFF/BLyS and APRIL, also demonstrated substantial therapeutic effects in patients with pSjD. The observed immunomodulatory effects of telitacicept, particularly the reduction in CD19+ B cells and the increase in CD8+ T cells, are consistent with the mechanisms proposed by studies of belimumab and ianalumab. While telitacicept and these other agents share similar therapeutic pathways, the dual-target mechanism of telitacicept might provide additional benefits by more comprehensively inhibiting B cell maturation and autoantibody production. Further studies with larger samples are warranted for head-to-head comparisons of these promising treatments. The safety profile of telitacicept observed in this case series aligns with findings from previous clinical trials. No serious adverse events were reported, consistent with phase II clinical trial data, which indicated similar infection rates between the telitacicept and placebo groups of pSjD patients [11]. The main adverse effect observed in this study was local injection site reactions, indicating that telitacicept may be a safe and well-tolerated treatment option for pSjD. This case series had several limitations. Firstly, the sample size was small, and the duration of telitacicept treatment varied among patients, with some using the drug for a short period due to financial constraints and the impact of the COVID-19 pandemic. Secondly, some patients had incomplete follow-up data, resulting in missing information. In addition, given the placebo effects on ESSDAI and ESSPRI scores in clinical trials of pSjD, it must be acknowledged that this case series lacked a control group, resulting in limited clinical insights. Another limitation is that all the patients in this study were selected from a single center in China, and the findings may not be generalizable to other ethnicities. Despite these limitations, the real-world data presented here provide valuable insights into the application of telitacicept in pSjD patients. Our findings suggest that telitacicept may confer improvements in disease activity and symptom burden, with a favorable tolerability among patients. This case series indicated that the individualized use of telitacicept in real-world settings may achieve similar efficacy and safety as observed in strictly selected trial participants. Despite these encouraging findings, larger and controlled clinical trials are warranted to provide more robust evidence on the efficacy and safety of telitacicept in pSjD treatment, ensuring a comprehensive understanding and validation of these preliminary findings. Jiajia Wu: data curation, writing – original draft, visualization. You Song: data curation, writing – original draft, investigation. Weiwei Wang: data curation, writing – original draft, investigation. Xujing Yuan: data curation, investigation, visualization. Rong Du: project administration, supervision, validation, writing – review and editing. The case series adhered to the principles outlined in the Declaration of Helsinki and received approval from the Medical Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (approve no. 2024–0077). As a retrospective study, the requirement for informed consent was waived by the Ethics Committee. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.