Contributions
Abstract: EP1491
Type: ePoster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Tumefactive demyelinating lesions (TDL) are typically defined as large demyelinating plaques (size >2cm) with mass effect, edema and contrast enhancement. According to literature, TDLs are present in about 2% of multiple sclerosis (MS) patients. Occurrence of TDLs under fingolimod treatment has been reported, but systematic studies about TDL frequency, clinical and MRI characteristics in fingolimod treated patients are lacking.
Aim: To report the clinical and magnetic resonance imaging (MRI) characteristics of four MS patients at our centre that developed TDLs during fingolimod treatment and to put this observation into the context of data on TDLs from phase 2 and 3 clinical trials with fingolimod.
Methods: Of approx. 300 fingolimod-treated patients at our centre, four (1.3%) had TDLs (excluding TDLs < 6 months after switching from natalizumab to fingolimod). The clinical trial safety database for the fingolimod phase 2 and the three phase 3 studies (FREEDOMS, FREEDOMS II, TRANSFORMS) was screened for subjects with T2-lesion volume increase >5000mm3 on study MRI to identify potential TDLs. Two neuroradiologists blinded for treatment subsequently reviewed the selected MRIs.
Results: Of the four patients with TDLs at our centre, two developed tumefactive lesions 7 and 10 months after treatment switch from natalizumab, while one patient developed a TDL after 3.5 years on fingolimod with prior interferon treatment and another patient after 10 months of first-line fingolimod treatment. All patients were clinically and/or radiologically active in the year(s) prior to the TDL.
MRI scans available from 3439 patients of the core phase 2 and 3 clinical trials were screened. 17/2317 (0.7%) fingolimod treated and 21/1122 (1.9%) in placebo or interferon beta treated met the 2 cm lesion size criteria. There was no increased risk for patients treated with fingolimod versus comparator (OR=0.77; CI 0.31,1.91; p=0.56) to experience TDLs. Detailed clinical and radiological findings will be presented.
Conclusion: Our data suggest that patients under fingolimod are not at higher risk of TDLs and that TDLs rather represent break through disease. Identification of factors contributing to these rare events would be desirable.
Disclosure:
AKP received research funding from the University of Basel, the Swiss National Science Foundation and Genzyme, travel support from Genzyme, support for educational activities from Baxalta and Merck and consulting fees from Bayer used for research support.
EWR and NML have nothing to disclose.
LZA, DB and MM are employees of Novartis.
JK received research support by an ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Science Foundation, Protagen AG, Roche, Genzyme and Novartis.
LK: institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation.
TD serves on scientific advisory boards for Novartis Pharma, Merck Serono, Biogen Idec, Genzyme, Mitsubishi Pharma, TEVA Pharma, GeNeuro, and Bayer Schering Pharma; has received funding for travel and/or speaker honoraria from Biogen Idec, Novartis, Merck Serono, and Bayer Schering Pharma; and receives research support from the Swiss National Research Foundation, Biogen Idec, Novartis Pharma, the European Union, and the Swiss MS Society. BD has nothing to disclose.
Abstract: EP1491
Type: ePoster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Tumefactive demyelinating lesions (TDL) are typically defined as large demyelinating plaques (size >2cm) with mass effect, edema and contrast enhancement. According to literature, TDLs are present in about 2% of multiple sclerosis (MS) patients. Occurrence of TDLs under fingolimod treatment has been reported, but systematic studies about TDL frequency, clinical and MRI characteristics in fingolimod treated patients are lacking.
Aim: To report the clinical and magnetic resonance imaging (MRI) characteristics of four MS patients at our centre that developed TDLs during fingolimod treatment and to put this observation into the context of data on TDLs from phase 2 and 3 clinical trials with fingolimod.
Methods: Of approx. 300 fingolimod-treated patients at our centre, four (1.3%) had TDLs (excluding TDLs < 6 months after switching from natalizumab to fingolimod). The clinical trial safety database for the fingolimod phase 2 and the three phase 3 studies (FREEDOMS, FREEDOMS II, TRANSFORMS) was screened for subjects with T2-lesion volume increase >5000mm3 on study MRI to identify potential TDLs. Two neuroradiologists blinded for treatment subsequently reviewed the selected MRIs.
Results: Of the four patients with TDLs at our centre, two developed tumefactive lesions 7 and 10 months after treatment switch from natalizumab, while one patient developed a TDL after 3.5 years on fingolimod with prior interferon treatment and another patient after 10 months of first-line fingolimod treatment. All patients were clinically and/or radiologically active in the year(s) prior to the TDL.
MRI scans available from 3439 patients of the core phase 2 and 3 clinical trials were screened. 17/2317 (0.7%) fingolimod treated and 21/1122 (1.9%) in placebo or interferon beta treated met the 2 cm lesion size criteria. There was no increased risk for patients treated with fingolimod versus comparator (OR=0.77; CI 0.31,1.91; p=0.56) to experience TDLs. Detailed clinical and radiological findings will be presented.
Conclusion: Our data suggest that patients under fingolimod are not at higher risk of TDLs and that TDLs rather represent break through disease. Identification of factors contributing to these rare events would be desirable.
Disclosure:
AKP received research funding from the University of Basel, the Swiss National Science Foundation and Genzyme, travel support from Genzyme, support for educational activities from Baxalta and Merck and consulting fees from Bayer used for research support.
EWR and NML have nothing to disclose.
LZA, DB and MM are employees of Novartis.
JK received research support by an ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Science Foundation, Protagen AG, Roche, Genzyme and Novartis.
LK: institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation.
TD serves on scientific advisory boards for Novartis Pharma, Merck Serono, Biogen Idec, Genzyme, Mitsubishi Pharma, TEVA Pharma, GeNeuro, and Bayer Schering Pharma; has received funding for travel and/or speaker honoraria from Biogen Idec, Novartis, Merck Serono, and Bayer Schering Pharma; and receives research support from the Swiss National Research Foundation, Biogen Idec, Novartis Pharma, the European Union, and the Swiss MS Society. BD has nothing to disclose.