Longitudinal Clinical and MRI Outcomes in Relapsing Multiple Sclerosis (RMS) Patients After Short-term Ponesimod Treatment Interruption and Re-initiation
Alexander Keenan1, Ludwig Kappos2, Maria Ait-Tihyaty3, Kavita Gandhi3, Ibrahim Turkoz3, Janice Wong3, Tatiana Sidorenko4, Fred Lublin5
1Janssen Global Services, LLC, NJ, USA, 2StatesNeurology and Research Center for Clinical Neuroimmunology and Neuroscience Basel, Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine and Biomedical Engineering University Hospital and University of Basel, Basel, Switzerland, 3Janssen Research & Development, LLC, Titusville, NJ, USA, 4Actelion Pharmaceuticals, Part of the Janssen Pharmaceutical Companies of Johnson & Johnson, Allschwil, Switzerland, 5Icahn School of Medicine at Mount Sinai, New York, NJ, USA
Objective:
To assess clinical and magnetic resonance imaging (MRI) outcomes in RMS patients at 48 weeks of follow-up after short-term interruption and re-initiation of ponesimod treatment.
Background:
Current multiple sclerosis (MS) disease-modifying treatments alter patients’ immune system due to different pharmacokinetic/pharmacodynamic profiles. Clinical situations such as pregnancies, infections or live vaccinations may require rapid drug elimination and a fully functioning immune system. Lymphocyte counts return to normal range in >90% of patients within 1 week of stopping ponesimod treatment. It is important to evaluate MS disease activity over time following ponesimod treatment interruption and re-initiation.
Design/Methods:
Patients who completed 108 weeks of ponesimod or teriflunomide treatment in the Phase-3 OPTIMUM study and underwent an accelerated elimination procedure were eligible for the open-label extension (OLE) study and received ponesimod 20mg. Of 567 patients randomized to ponesimod in OPTIMUM, 439 (77.4%) entered the OLE and 239 (42.2%) had ≥48 weeks of follow up. The annualized relapse rate (ARR) and cumulative number of combined-unique-active-lesions (CUALs) following short-term treatment interruption (between OPTIMUM and OLE) and re-initiation (at start of the OLE) were evaluated in 239 patients.
Results:
The mean duration of ponesimod treatment interruption (between the end of OPTIMUM and initiation of OLE) was 17.6 days (range 13-45). The ARR at OLE week 48, and considering treatment interruption and re-initiation, was 0.191 (95% CI:0.140, 0.261). This was numerically lower than the 2-year ARR of 0.234 (95% CI: 0.186, 0.296) with a relative rate reduction (RRR) of 18.4% (RRR: 0.816, 95% CI: 0.595, 1.120). At OLE week 48, patients had 1.73 CUALs/year (95% CI:1.30, 2.31), which was not statistically significantly different from 1.48 CUALs/year (95% CI: 1.19, 1.82) in OPTIMUM.
Conclusions:
Based on clinical and imaging outcomes at 48 weeks following short-term interruption and re-initiation of ponesimod, disease activity remained consistent with that observed prior to interruption.