Contributions
Abstract: 101
Type: Young Scientific Investigators' Session
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Disease modifying treatment (DMT) is available for early/relapsing MS, however no licensed DMT exists for people with EDSS >6.5. Recently licensed for highly active relapsing MS, cladribine is also a promising candidate DMT for people with MS (pwMS) at all stages of disability.
Aims & objectives: To report our experience using subcutaneous (s.c.) cladribine personalised dosing (cladribine PD) in pwMS.
Methods: Cladribine PD was offered to pwMS meeting NHS England (NHSE) criteria for licensed DMT, but chose cladribine PD instead, and as a compassionate treatment in pwMS not eligible for NHSE DMT. Disease activity was based on the clinical course and either (i) new lesions on MRI and/or (iii) elevated CSF neurofilament light chain levels. Safety assessments ruled out latent infections, and compliance with regular cervical cancer screening was mandatory. Cladribine 10mg s.c. was administered on three consecutive days (four in pwMS >90kg) during week 1. Based on total lymphocyte count at week 4, patients were given another 0-3 injections in week 5. A second course of treatment was given after 48 weeks. Follow-up included annual MRI head and three monthly blood counts.
Results: Over 200 pwMS (median age: 46 years) were screened; 171 (107 women, 64 men) underwent at least one treatment course; disease duration was 11 (SD=±8) years. At baseline 80/171 pwMS were treatment naive; 91/171 switched from a different DMT; 83/171 did not fulfill NHSE DMT criteria. 128/171 received full dose (60-70mg) at first course; in 43/171 dose was reduced due to lymphopenia (WHO grade ≤2 in 50%; grade 3 in 2%). 75/171 patients completed a second course; 33/75 received full dose; in 42/75 dose was reduced. Cladribine PD was well tolerated. Adverse events included mild injection site reactions (3), skin rash (3), shingles (2), aspiration pneumonia (2), allergic reaction (1), stye (1), dental infection (1), UTIs, and pain (chest, musculo-skeletal, head). Baseline EDSS was 4.7 (SD=±2.2). In 75 pwMS completing two courses of cladribine PD, median EDSS improved in 9 (12%), remained stable in 42 (56%) and worsened in 24 (32%).
Conclusion: Cladribine PD was generally safe and prevented grade 3 lymphopenia in all but 2% of pwMS. It offers an alternative in pwMS eligible for NHSE-funded DMT, and for pwMS not eligible for NHSE-funded DMT with MRI and/or CSF detectable disease activity. Follow-up of this cohort continues to further assess safety and long-term efficacy.
Disclosure: None considered relevant. However ZM, CAG, KAP, SDT, OY, TC, AA, ME and JM have nothing to declare; BJP has received honoraria from Roche, Teva, Novartis, Merck-Serono, Sanofi-Genzyme and Biogen; MM has received honoraria or meeting support from Novartis, Genzyme and AbbVie; DB is a founder and consultant to Canbex therapeutics and has received research funds from Canbex therapeutics, Sanofi-Genzyme and Takeda. GG has received fees for participation in advisory board for AbbVie Biotherapeutics, Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, Roche, Sanofi Genzyme, Synthon, Teva and Vertex; speaker fees from AbbVie, Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis and Teva. Research support from Biogen, Genzyme, Ironwood, Merck, Merck Serono and Novartis; SG has received honoraria and meeting support from Biogen, Novartis, Teva, Genzyme and research funds from Genzyme. KS has been a PI of trials sponsored by Novartis, Roche and Teva and involved in trials sponsored by Biogen, Sanofi-Genzyme, BIAL, Cytokinetics, and Canbex and has received honoraria and meeting support from Biogen, Lipomed, Merck, Merck Serono, Novartis and Teva.
Abstract: 101
Type: Young Scientific Investigators' Session
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Disease modifying treatment (DMT) is available for early/relapsing MS, however no licensed DMT exists for people with EDSS >6.5. Recently licensed for highly active relapsing MS, cladribine is also a promising candidate DMT for people with MS (pwMS) at all stages of disability.
Aims & objectives: To report our experience using subcutaneous (s.c.) cladribine personalised dosing (cladribine PD) in pwMS.
Methods: Cladribine PD was offered to pwMS meeting NHS England (NHSE) criteria for licensed DMT, but chose cladribine PD instead, and as a compassionate treatment in pwMS not eligible for NHSE DMT. Disease activity was based on the clinical course and either (i) new lesions on MRI and/or (iii) elevated CSF neurofilament light chain levels. Safety assessments ruled out latent infections, and compliance with regular cervical cancer screening was mandatory. Cladribine 10mg s.c. was administered on three consecutive days (four in pwMS >90kg) during week 1. Based on total lymphocyte count at week 4, patients were given another 0-3 injections in week 5. A second course of treatment was given after 48 weeks. Follow-up included annual MRI head and three monthly blood counts.
Results: Over 200 pwMS (median age: 46 years) were screened; 171 (107 women, 64 men) underwent at least one treatment course; disease duration was 11 (SD=±8) years. At baseline 80/171 pwMS were treatment naive; 91/171 switched from a different DMT; 83/171 did not fulfill NHSE DMT criteria. 128/171 received full dose (60-70mg) at first course; in 43/171 dose was reduced due to lymphopenia (WHO grade ≤2 in 50%; grade 3 in 2%). 75/171 patients completed a second course; 33/75 received full dose; in 42/75 dose was reduced. Cladribine PD was well tolerated. Adverse events included mild injection site reactions (3), skin rash (3), shingles (2), aspiration pneumonia (2), allergic reaction (1), stye (1), dental infection (1), UTIs, and pain (chest, musculo-skeletal, head). Baseline EDSS was 4.7 (SD=±2.2). In 75 pwMS completing two courses of cladribine PD, median EDSS improved in 9 (12%), remained stable in 42 (56%) and worsened in 24 (32%).
Conclusion: Cladribine PD was generally safe and prevented grade 3 lymphopenia in all but 2% of pwMS. It offers an alternative in pwMS eligible for NHSE-funded DMT, and for pwMS not eligible for NHSE-funded DMT with MRI and/or CSF detectable disease activity. Follow-up of this cohort continues to further assess safety and long-term efficacy.
Disclosure: None considered relevant. However ZM, CAG, KAP, SDT, OY, TC, AA, ME and JM have nothing to declare; BJP has received honoraria from Roche, Teva, Novartis, Merck-Serono, Sanofi-Genzyme and Biogen; MM has received honoraria or meeting support from Novartis, Genzyme and AbbVie; DB is a founder and consultant to Canbex therapeutics and has received research funds from Canbex therapeutics, Sanofi-Genzyme and Takeda. GG has received fees for participation in advisory board for AbbVie Biotherapeutics, Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, Roche, Sanofi Genzyme, Synthon, Teva and Vertex; speaker fees from AbbVie, Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis and Teva. Research support from Biogen, Genzyme, Ironwood, Merck, Merck Serono and Novartis; SG has received honoraria and meeting support from Biogen, Novartis, Teva, Genzyme and research funds from Genzyme. KS has been a PI of trials sponsored by Novartis, Roche and Teva and involved in trials sponsored by Biogen, Sanofi-Genzyme, BIAL, Cytokinetics, and Canbex and has received honoraria and meeting support from Biogen, Lipomed, Merck, Merck Serono, Novartis and Teva.