Abstract

Background: Raynaud's phenomenon (RP) represents one of the main features and causes of comorbidity in patients with Systemic Sclerosis (SSc). Dihydropyridine calcium-channel blockers (CCB) are recommended as first-line treatment for SSc-RP; in particular, modified-release (MR)-nifedipine is the most frequently employed. On the other hand, there is a lack of data regarding new-generation dihydropyridine CCBs, such as barnidipine, which has the potential to be an effective alternative to nifedipine in RP, since its long-lasting slow-onset vasodilatative effect. Objectives: The present study aims to assess short-term barnidipine efficacy and tolerability in SSc-RP compared to MR-nifedipine. Methods: Prospective observational study of patients diagnosed with SSc according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria starting barnidipine 10 mg/day between January 2021 and March 2023. RP severity was assessed using Raynaud's Condition Score (RCS) alongside mean blood pressure (MBP) measurement at baseline and 3 months follow-up or discontinuation visit. The control group was made up of retrospectively evaluated patients with SSc who started MR-nifedipine 20 mg/day between January 2019 and March 2023. For both groups, we excluded patients starting another vasoactive drug during the observation period (6 months) and data about CCB discontinuation and adverse events (AEs) related to the CCB in the first six months of treatment, along with relevant clinical data were collected. Differences between groups were assessed using Student's T or Mann Whitney's U tests, or Chi-Square tests with Fisher's exact test when required. Retention rate of the two CCBs was analyzed using Kaplan-Meier survival analysis with the event being CCB discontinuation. The two curves were compared using the log-rank test. Univariate logistic regression was employed to assess possible predictors of barnidipine discontinuation. Results: We enrolled 64 patients, 29 (45.3%) started barnidipine, and 35 (54.7%) started MR-nifedipine. Most patients starting barnidipine had a previous CCB exposure (69%, of which MR-nifedipine 55.2%), most commonly withdrawn for AEs (57.9%). After starting barnidipine, RCS decreased significantly (6.6 ± 1.8 vs 4.4 ± 1.8, p<0.001), while the MBP did not change significantly (86.4 ± 8.4 vs 85 ± 7.3 mmHg; p= 0.36). Overall, nine patients (31%) discontinued barnidipine during the follow-up (AEs 6/9), inefficacy 3/9). The retention rates at 6 months (Figure 1) of barnidipine and MR-nifedipine did not differ significantly (69 vs 80%; log-rank p=0.23), and the two groups had a similar incidence of AEs leading to discontinuation (20.1 vs 17%; p=0.48), the most commonly reported being headache (38.5%), hypotension (30.8%), palpitations, flushing, and edema (7.7% each). No serious AE was reported in any group. In univariate binomial logistic regression, no correlation was found between barnidipine withdrawal and previous CCB failure (β=0.188; 95%CI [0.02-1.8]; p=0.147) or concomitant oral vasoactive drug therapy (β=1.5; 95%CI [0.24-9.44]; p=0.67). No difference was found between patients withdrawing and continuing barnidipine in terms of age, disease duration, female gender, baseline MBP, RCS, and BMI. Conclusion: Barnidipine could be an effective and well-tolerated therapeutic option to treat SSc-RP, even in patients previously failing other CCBs and in combination with PDE5i or ERA. REFERENCES: [1] Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017; 76: 1327–1339. [2] Khouri C, Lepelley M, Bailly S, et al. Comparative efficacy and safety of treatments for secondary Raynaud's phenomenon: a systematic review and network meta-analysis of randomised trials. Lancet Rheumatol 2019; 1: e237–e246. Acknowledgements: NIL. Disclosure of Interests: None declared.