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OBJECTIVE: To investigate the clinical response at week 52 in patients with ankylosing spondylitis (AS) who received secukinumab 300 vs 150 mg after inadequate response to 150 mg at week 16. METHODS: ASLeap (NCT03350815) was a randomized, double-blind, parallel-group, multicentre, phase 4 trial. After 16 weeks of open-label secukinumab 150 mg (Treatment Period 1), patients who did not achieve inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] <1.3) at both Weeks 12 and 16 were considered to have an inadequate response and were randomized 1:1 to receive secukinumab 300 or 150 mg every 4 weeks until week 52 (Treatment Period 2). The primary efficacy variable was achievement of ASDAS <1.3 at week 52 using week 16 as baseline. Safety was evaluated by the incidence of treatment-emergent adverse events through week 52. RESULTS: Of 322 patients treated with secukinumab in Treatment Period 1, 207 (64.3%) had inadequate response. Similar proportions of patients with inadequate response randomized to secukinumab 300 mg (n = 101) and 150 mg (n = 105) in Treatment Period 2 completed the study (83.8% and 84.3%, respectively). At week 52, 8.8% and 6.7% of patients receiving secukinumab 300 and 150 mg, respectively, achieved ASDAS <1.3. The incidence of treatment-emergent adverse events was similar in both groups through week 52. No new safety signals were observed. CONCLUSION: Patients with AS who did not achieve ASDAS <1.3 after receiving secukinumab 150 mg for 16 weeks experienced similar clinical response and safety through week 52 regardless of dose escalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03350815.
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Background: Fingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood. Objective: Investigate fingolimod's temporal effects on immune cell subsets, and safety outcomes. Methods: In FLUENT, a 12-month, prospective, non-randomized, open-label, phase IV study, adult participants received fingolimod 0.5â mg/day. Changes in immune cell subsets, anti-John Cunningham virus (JCV) antibody index, and serum neurofilament levels were assessed. Results: 165 fingolimod-naive and 217 participants treated for 2-12 years in routine clinical practice were enrolled. Levels of all monitored peripheral lymphocyte subsets were reduced from month 3 in fingolimod-naive participants. Greatest reductions occurred in naive and central memory CD4+ and CD8+ T cells, and in naive and memory B cells. Most lymphocyte subset levels remained stable in the continuous fingolimod group. Components of the innate immune system remained within reference ranges. No increase in JCV seropositivity was observed. No single cellular subset correlated with anti-JCV antibody index at any time point. Neurofilament levels remained within healthy adult reference limits throughout. No opportunistic infections were reported; no new or unexpected safety signals were observed. Conclusion: FLUENT provides insights into the utility of immunological profiling to evaluate therapy response and potential infection risk.