KD-023

Compare the efficacy of tofacitinib and BAFF inhibitor (belimumab and telitacicept) in mild to moderate systemic lupus erythematosus patients.

Overall, 33 patients treated with tofacitinib and 34 patients treated with BAFF inhibitor (23 patients underwent belimumab and 11 patients underwent telitacicept) were enrolled in this study. The patients were evaluated at 1, 3, 6, and 12 months after the baseline. The primary endpoint was set as the proportion of patients who achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response.

At 3 months, BICLA responses were achieved in 27 (81.8%) patients treated with tofacitinib and 18 (52.9%) individuals treated with BAFF inhibitor. The BICLA response rate of tofacitinib is significantly higher than that of BAFF inhibitor (p = 0.012). Meanwhile, there was no discernible difference between the patients in the tofacitinib-treated group and the BAFF inhibitor-treated group in terms of the 3-month arthritis resolution rate (p = 0.117) or the mucocutaneous resolution rate (p = 0.175). Only one patient reported adverse events in the TOFA group during the 1-year follow-up. No severe adverse events, including infections, thromboembolic events, or deaths, were reported in both groups.

Compared to BAFF inhibitors, tofacitinib showed the potential efficacy in individuals with mild to moderate SLE. The results paved the way to optimal utilization of tofacitinib in SLE patients. Key Points • BAFF inhibitor is recommended as first-/second-line therapy for mild to moderate SLE patients. • The rapid efficacy of tofacitinib in treating mucocutaneous involvement and arthritis in lupus has been demonstrated. • This study firstly compares tofacitinib with BAFF inhibitor in SLE patients, suggesting that tofacitinib can faster achieve promising therapeutic effects in mild to moderate SLE patients.

Organic acids are often used as pH modifiers in extended-release (ER) formulations to achieve pH-independent release of weakly basic drugs. These acids are intended to enhance drug release at intestinal pH by modifying the microenvironmental pH within the tablet matrix, thus reducing the pH-dependence of the drug release. However, the effectiveness of this approach depends on multiple factors, including the physicochemical properties of both the drug and the pH modifiers, formulation compositions, and drug loading. This study investigates the influence of pH modifiers on the pH-dependent release from ER hydrophilic matrix tablets containing four highly soluble acidic excipients using to facitinib (TOFA) as a model drug. The results demonstrated that the pH-dependence of TOFA release could be reduced to varying degrees depending on the specific acid used. Analysis of both drug and polymer release profiles indicated that the reduced pH-dependence was due not only to localized pH modulation, but also interactions between the acids and TOFA, as well as between acids and rate-controlling polymers. These findings provide valuable insights into the key factors that can influence the design of pH-independent ER hydrophilic matrix tablets for drugs with pH-dependent solubility.