Contributions
Abstract: 206
Type: Scientific Session
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Recurrence of disease activity (RDA) after cessation of disease modifying treatments (DMT) is frequently observed in multiple sclerosis (MS). DMTs reducing lymphocyte trafficking into the central nervous system have been associated with a higher risk and severity of RDA after discontinuation.
Aims and Methods: Retrospective analysis of a real-world MS cohort to describe characteristics of RDA within 6 months (m) after fingolimod (FGL) discontinuation. RDA was defined as either clinical and/or MRI activity. Severe RDA was defined as either severe relapse (EDSS increase ≥2 points) and/or pronounced MRI activity.
Results: Out of 433 patients who initiated FGL treatment in our MS center we identified 110 who discontinued FGL after a mean treatment duration of 26,2±18,9m (83% RRMS, 17% SPMS, 72% female, mean disease duration at discontinuation 9,6±7 years (y)). As 7 patients discontinued FGL more than once, a total of 118 discontinuation events were registered (37 with no subsequent DMT within 6m, 10 after FGL break < 6m, and 71 with switch to another DMT (median interval 4 weeks (w) (IQR 4-6): 39 switched to rituximab (RTX) or ocrelizumab (OCZ), 11 to Natalizumab (NTZ), 10 to dimethylfumarate (DMF), 3 to teriflunomide, 7 to platform injectables (PI) and 1 to Azathioprine).
Within 6m after FGL discontinuation (median time until relapse 8w (IQR 4-16) we observed 41 events of RDA (23 both clinical and radiological, 12 clinical only, 6 MRI activity only) in 39 patients (36 RRMS, 3 SPMS)). 15 RDA events occurred in patients with no subsequent DMT, 4 in patients who discontinued FGL < 6m and 22 in patients who switched to another DMT (11 to RTX/OCZ, 4 to NTZ, 2 to DMF, 5 to PI). Patients with RDA had more frequently experienced disease activity in the year before stopping FGL (relapses 52,4% vs. 37,7%; MRI activity 54,8% vs. 39%), were younger at time of discontinuation (34,4±10y vs. 43±10,7y) and had a shorter disease duration (6,6±5,5y vs. 10,6±7,4y). In 12 patients we observed 14 severe RDA events (2 with no subsequent DMT, 12 after switching DMT (6 to RTX/OCZ, 2 to NTZ, 3 to PI, 1 to DMF)). 4/14 severe and none of the other RDA events had a confirmed disability worsening of ≥1 EDSS point after a median follow-up of 6m since relapse.
Conclusion: RDA after FGL discontinuation occurred in around 30% of all cases. Younger MS patients with shorter disease duration and evidence of disease activity on treatment with FGL carried a higher risk of RDA.
Disclosure: - Nuria Cerda: no disclosures. NC received ECTRIMS MS clinical training fellowship programme 2017.
- Sara Nagy: no disclosures
- Tim Sinnecker: has received travel support from Actelion and Roche, and speaker fees from Biogen. He is employee of the Medical Image Analysis Center AG in Basel.
- Jens Würfel: CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministeries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI).
- Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
- Özgür Yaldizli received for his institution (University Hospital Basel) grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.
- Ludwig Kappos´ institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
- Tobias Derfuss received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme; he received research support from Biogen, Novartis, Swiss National Research Foundation, University of Basel, and Swiss MS Society.
Bernhard Décard received for the institution (University Hospital Basel) travel support and / or fees from advisory boards or speaker fees from Allmirall, Biogen, Genzyme, Roche, Teva and Novartis, that were used exclusively for research support.
Abstract: 206
Type: Scientific Session
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Recurrence of disease activity (RDA) after cessation of disease modifying treatments (DMT) is frequently observed in multiple sclerosis (MS). DMTs reducing lymphocyte trafficking into the central nervous system have been associated with a higher risk and severity of RDA after discontinuation.
Aims and Methods: Retrospective analysis of a real-world MS cohort to describe characteristics of RDA within 6 months (m) after fingolimod (FGL) discontinuation. RDA was defined as either clinical and/or MRI activity. Severe RDA was defined as either severe relapse (EDSS increase ≥2 points) and/or pronounced MRI activity.
Results: Out of 433 patients who initiated FGL treatment in our MS center we identified 110 who discontinued FGL after a mean treatment duration of 26,2±18,9m (83% RRMS, 17% SPMS, 72% female, mean disease duration at discontinuation 9,6±7 years (y)). As 7 patients discontinued FGL more than once, a total of 118 discontinuation events were registered (37 with no subsequent DMT within 6m, 10 after FGL break < 6m, and 71 with switch to another DMT (median interval 4 weeks (w) (IQR 4-6): 39 switched to rituximab (RTX) or ocrelizumab (OCZ), 11 to Natalizumab (NTZ), 10 to dimethylfumarate (DMF), 3 to teriflunomide, 7 to platform injectables (PI) and 1 to Azathioprine).
Within 6m after FGL discontinuation (median time until relapse 8w (IQR 4-16) we observed 41 events of RDA (23 both clinical and radiological, 12 clinical only, 6 MRI activity only) in 39 patients (36 RRMS, 3 SPMS)). 15 RDA events occurred in patients with no subsequent DMT, 4 in patients who discontinued FGL < 6m and 22 in patients who switched to another DMT (11 to RTX/OCZ, 4 to NTZ, 2 to DMF, 5 to PI). Patients with RDA had more frequently experienced disease activity in the year before stopping FGL (relapses 52,4% vs. 37,7%; MRI activity 54,8% vs. 39%), were younger at time of discontinuation (34,4±10y vs. 43±10,7y) and had a shorter disease duration (6,6±5,5y vs. 10,6±7,4y). In 12 patients we observed 14 severe RDA events (2 with no subsequent DMT, 12 after switching DMT (6 to RTX/OCZ, 2 to NTZ, 3 to PI, 1 to DMF)). 4/14 severe and none of the other RDA events had a confirmed disability worsening of ≥1 EDSS point after a median follow-up of 6m since relapse.
Conclusion: RDA after FGL discontinuation occurred in around 30% of all cases. Younger MS patients with shorter disease duration and evidence of disease activity on treatment with FGL carried a higher risk of RDA.
Disclosure: - Nuria Cerda: no disclosures. NC received ECTRIMS MS clinical training fellowship programme 2017.
- Sara Nagy: no disclosures
- Tim Sinnecker: has received travel support from Actelion and Roche, and speaker fees from Biogen. He is employee of the Medical Image Analysis Center AG in Basel.
- Jens Würfel: CEO of MIAC AG Basel, Switzerland. He served on scientific advisory boards of Actelion, Biogen, Genzyme-Sanofi, Novartis, and Roche. He is or was supported by grants of the EU (Horizon2020), German Federal Ministeries of Education and Research (BMBF) and of Economic Affairs and Energy (BMWI).
- Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
- Özgür Yaldizli received for his institution (University Hospital Basel) grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.
- Ludwig Kappos´ institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
- Tobias Derfuss received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme; he received research support from Biogen, Novartis, Swiss National Research Foundation, University of Basel, and Swiss MS Society.
Bernhard Décard received for the institution (University Hospital Basel) travel support and / or fees from advisory boards or speaker fees from Allmirall, Biogen, Genzyme, Roche, Teva and Novartis, that were used exclusively for research support.