
Contributions
Abstract: P1258
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background and goals: The landscape of therapies available to treat relapsing multiple sclerosis (MS) continues to expand. As a result clinicians are faced with significant challenges in deciding optimum treatment strategies for individual patients which is influenced by a number of factors including the degree of clinical and radiological disease activity, JC virus antibody status, potential adverse effects of drugs and sequential treatment risks. We report a case series of 9 patients treated with alemtuzumab after discontinuation of fingolimod with significant early rebound disease activity. We suggest potential underlying mechanisms and highlight the importance of this phenomenon for patient management.
Methods: Patients with relapsing MS treated with fingolimod and subsequently alemtuzumab were identified by personal communication with 6 European neuroscience centres. History was obtained by clinical note review.
Results: 9 patients (5 female, median follow-up 15 months (range 8-22)) were identified who had received alemtuzumab following fingolimod. All patients had undergone a therapeutic escalation strategy prior to treatment with fingolimod with 8/9 also having previously received natalizumab. In 5/9 patients lymphocyte counts had not recovered to normal range prior to alemtuzumab and in 4 patients lymphocytes reconstituted more rapidly than expected. 8/9 patients experienced at least one clinical relapse soon after starting alemtuzumab, with active radiological disease seen in all patients.
Conclusions: We postulate that rebound activity in these patients is caused by a significant number of lymphocytes remaining "hidden" from the usual intravascular therapeutic effects of alemtuzumab as a result of selective lymphoid sequestration. Subsequent CD52 positive lymphocyte egress from lymph nodes then initiates the observed rebound inflammatory disease activity. The repopulating immune repertoire is also likely to be considerably different to that normally observed post alemtuzumab. Further systematic observational studies are required to confirm these phenomena. In addition future trials addressing longer-term outcomes of induction and escalation paradigms need to be designed in order to guide clinicians on strategies for treatment switches. In particular, careful consideration needs to be given to mode of action of individual therapies and sequential treatment effects.
Disclosure: M Willis has nothing to declare.
O Pearson has received honoraria and support to attend scientific meetings, speakers´ fees, and advisory boards from Biogen, Genzyme, Novartis, Teva, Merck Serono and Roche.
Z Illes has nothing to declare.
T Sejbaek"s PhD is supported by Biogen Idec.
C Nielsen has nothing to declare.
M Duddy: Speakers fees, advisory boards, hospitality for educational meetings, participation in collaborative studies: Bayer, Biogen, Genzyme, Merck, Novartis, Roche, Teva
K Petheram: Speaker/meeting fees from Genzyme and Novartis. Travel/hospitality from Genzyme and Biogen.
C van Munster has received travel support from Novartis Pharma AG and Teva, and honoraria for lecturing and consulting from Biogen-Idec and Merck.
J Killestein has accepted speaker and consultancy fees from Merck-Serono, Teva, Biogen, Genzyme and Novartis.
B Uitdehaag has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA.
C Malmestrom has recived lecture honoraria and served at ad-boards for Biogen, Genzyme, Merck and Novartis.
E Tallantyre has received salary from Biogen Idec as part of a fellowship in addition to a travel bursary.
N Robertson has received funding from Novartis and from Genzyme for a neuroimmunology fellow.
Abstract: P1258
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background and goals: The landscape of therapies available to treat relapsing multiple sclerosis (MS) continues to expand. As a result clinicians are faced with significant challenges in deciding optimum treatment strategies for individual patients which is influenced by a number of factors including the degree of clinical and radiological disease activity, JC virus antibody status, potential adverse effects of drugs and sequential treatment risks. We report a case series of 9 patients treated with alemtuzumab after discontinuation of fingolimod with significant early rebound disease activity. We suggest potential underlying mechanisms and highlight the importance of this phenomenon for patient management.
Methods: Patients with relapsing MS treated with fingolimod and subsequently alemtuzumab were identified by personal communication with 6 European neuroscience centres. History was obtained by clinical note review.
Results: 9 patients (5 female, median follow-up 15 months (range 8-22)) were identified who had received alemtuzumab following fingolimod. All patients had undergone a therapeutic escalation strategy prior to treatment with fingolimod with 8/9 also having previously received natalizumab. In 5/9 patients lymphocyte counts had not recovered to normal range prior to alemtuzumab and in 4 patients lymphocytes reconstituted more rapidly than expected. 8/9 patients experienced at least one clinical relapse soon after starting alemtuzumab, with active radiological disease seen in all patients.
Conclusions: We postulate that rebound activity in these patients is caused by a significant number of lymphocytes remaining "hidden" from the usual intravascular therapeutic effects of alemtuzumab as a result of selective lymphoid sequestration. Subsequent CD52 positive lymphocyte egress from lymph nodes then initiates the observed rebound inflammatory disease activity. The repopulating immune repertoire is also likely to be considerably different to that normally observed post alemtuzumab. Further systematic observational studies are required to confirm these phenomena. In addition future trials addressing longer-term outcomes of induction and escalation paradigms need to be designed in order to guide clinicians on strategies for treatment switches. In particular, careful consideration needs to be given to mode of action of individual therapies and sequential treatment effects.
Disclosure: M Willis has nothing to declare.
O Pearson has received honoraria and support to attend scientific meetings, speakers´ fees, and advisory boards from Biogen, Genzyme, Novartis, Teva, Merck Serono and Roche.
Z Illes has nothing to declare.
T Sejbaek"s PhD is supported by Biogen Idec.
C Nielsen has nothing to declare.
M Duddy: Speakers fees, advisory boards, hospitality for educational meetings, participation in collaborative studies: Bayer, Biogen, Genzyme, Merck, Novartis, Roche, Teva
K Petheram: Speaker/meeting fees from Genzyme and Novartis. Travel/hospitality from Genzyme and Biogen.
C van Munster has received travel support from Novartis Pharma AG and Teva, and honoraria for lecturing and consulting from Biogen-Idec and Merck.
J Killestein has accepted speaker and consultancy fees from Merck-Serono, Teva, Biogen, Genzyme and Novartis.
B Uitdehaag has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA.
C Malmestrom has recived lecture honoraria and served at ad-boards for Biogen, Genzyme, Merck and Novartis.
E Tallantyre has received salary from Biogen Idec as part of a fellowship in addition to a travel bursary.
N Robertson has received funding from Novartis and from Genzyme for a neuroimmunology fellow.