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Introduction: Ozanimod is a sphingosine 1-phosphate receptor 1 and 5 modulator approved in multiple countries for treatment of adults with relapsing forms of MS (RMS) or moderately to severely active ulcerative colitis. Objective(s): To describe incidence rates (IRs) of treatmentemergent adverse events (TEAEs) in patients with RMS treated with ozanimod 0.92 mg in phase 3 and open-label extension (OLE) trials. Method(s): In phase 3 trials, adults with RMS were randomised to oral ozanimod 0.46 or 0.92 mg/d or intramuscular interferon beta-1a 30 mug/wk for >=12 months (SUNBEAM-NCT02294058) or 24 months (RADIANCE-NCT02047734). Completers were eligible to enrol in the ongoing OLE trial (DAYBREAK-NCT02576717) of ozanimod 0.92 mg/d. IRs and 95% confidence intervals (CI)/1000 person years (PY;100,000 PY for malignancies) were calculated for TEAEs during the pooled phase 3 trials and at yearly intervals during the OLE (2 Feb 2021 cutoff). Result(s): In patients treated with continuous ozanimod 0.92 mg (n=882), the IR [95%CI]/1000 PY decreased over time (from phase 3 to OLE >36 months) for overall TEAEs (896.1 [826.8-971.3] vs 259.1 [180.0-372.8]);infections (300.5 [268.9-335.9] vs 144.9 [109.2-192.3]);opportunistic infections (12.0 [7.4-19.6] vs 4.3 [1.4-13.3]);cardiac disorder TEAEs (22.8 [16.0-32.7] vs 4.2 [1.4-13.0]);and hepatic disorder TEAEs (77.0 [63.1-94.0] vs 15.1 [8.1-28.1]). The most common opportunistic infections in phase 3 trials and the OLE were oral herpes and herpes zoster (including varicella zoster virus). IRs remained relatively stable for serious TEAEs (31.2 [23.0-42.4] vs 30.5 [19.7-47.3]), malignancies (372.2 [120.8-868.5] vs 276.7 [33.5-999.6]/100,000 PY), confirmed macular edema (n/N, 1/882;0.7 [0.1-5.3] vs n/N, 1/687;1.4 [0.2-9.8]), and pulmonary TEAEs (11.3 [6.8-18.7] vs 0.0 [0.0-9.9]). The IR for serious infections remained relatively stable until OLE >36 months, at which time the IR increased (6.7 [3.5-12. 9] vs 9.8 [4.7-20.6]), which may be partially due to the COVID-19 pandemic. The most common serious infections were appendicitis (n/N, 3/882) and pyelonephritis acute (n/N, 1/882) (phase 3), and pneumonia (n/N, 4/762) and coronavirus infection (n/N, 3/762) (OLE). Most coronavirus infections were nonserious (31/34 [91.2%]). Conclusion(s): In this post hoc analysis, IRs of TEAEs in patients with RMS treated with continuous ozanimod 0.92 mg in phase 3 and OLE trials generally declined or remained stable over up to 5 years of observation time.
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Objective(s): Gaps in current evidence and guidance leave clinicians with unanswered questions on the use of cladribine tablets for the treatment of multiple sclerosis (MS) during the COVID-19 pandemic, particularly relating to COVID-19 vaccination. We describe a consensus-based program led by international MS experts with the aim of supplementing current guidelines and treatment labels by providing timely recommendations relating to COVID-19 vaccination and the use of cladribine tablets in clinical practice. Material(s) and Method(s): A steering committee (SC) of 10 international MS experts identified seven clinical questions to answer concerning the use of cladribine tablets and COVID-19 vaccination, which addressed issues relating to patient selection, timing and efficacy, and safety. Clinical recommendations addressing each question were drafted using available evidence combined with expert opinion from the SC. An extended faculty of 28 MS experts, representing 19 countries, in addition to the SC members, voted on the recommendations. Consensus on recommendations was achieved when ≥75% of respondents expressed an agreement score of 7–9, on a 9-point scale. Result(s): Consensus was achieved on all 13 recommendations. Clinical recommendations are provided on whether all patients with MS receiving cladribine tablets should be vaccinated against COVID-19, and whether they should be prioritized;the timing of vaccination around dosing of cladribine tablets (i.e., before and after a treatment course);and the safety of COVID-19 vaccination for these patients. Conclusion(s): There was overwhelming consensus that the risks of COVID-19 outweigh risks of vaccination in people with MS who are being treated with cladribine tablets, and all people with MS treated with cladribine tablets should be vaccinated against COVID-19 as soon as possible, unless they have a contraindication. The consensus provides timely guidance on patient selection, timing, efficacy, and safety of COVID-19 vaccination in patients receiving cladribine tablets, which is relevant to decision-making in everyday clinical practice.
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Introduction: Multiple sclerosis is the major cause of non-traumatic disability in young people, reducing their ability to work. Natalizumab has been shown to improve productivity in previous European observational studies. Objectives: To assess natalizumab impact on the productivity at work in employed patients with Relapsing-Remitting Multiple Sclerosis (RR-MS) in France, by comparing the year before and after treatment initiation. Methods: TITAN is an observational, open-label, multicenter and national study. Patients were included between June 2017 and December 2019. Phone interviews were held at baseline and 12 months after treatment initiation with the patients to collect information on their professional situation, work stoppages and daily discomfort. An additional survey was carried out to collect changes during the COVID19 lockdown. This interim analysis mainly assessed changes in productivity at 12 months (M12) (number of worked hours before and after study enrollment), in the WPAI and the MSIS29. Results: Out of the 185 included patients, 140 (75.7%) were women, aged of 36.4 (+/- 9.5) years. The median EDSS score was of 2.0 and the median time since MS diagnosis of 3 years. Most patients had permanent contracts (82%), worked a high number of hours/year at baseline (mean: 1295 +/- 495) and 67% of them had at least one work stoppage in the previous year. At M12, 77% of patients remained in an equivalent employment status. The annualized worked hours remained stable (median = 1389 h/y at M0 vs. 1348 h/y at M12;p-value: 0.12), regardless the type of contract. During the pandemic period, the annualized median productivity dropped from 1384 h/y (between M0 and the lockdown) to 566 h/y (after the lockdown), regardless the type of contract. The ability to perform daily activities has improved significantly within 12 months after natalizumab initiation (WPAI;p-value: <0.01 38% of discomfort at M0 vs. 29% at M12). The MSIS29 highlights a significant reduction in the physical impact (19.7% at M0 to 16.8 % at M12;p-value: 0.01) and psychological impact of MS (32.2% at M0 to 26.7% at M12;p-value: 0.001). Conclusions: While the number of hours worked did not change significantly, patients treated with natalizumab had a significant qualitative improvement in work discomfort and impact of MS.