Abstract: P1182
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Anti-CD52 IgG ALE provides powerful, long-term (LT), disease-modifying effects with a liability for infusion-related, infectious, and autoimmune side effects; we present a large clinic cohort of highly treatment-refractory, older, higher disability subjects with LT data.
Objectives: Report complications of hospitalization, infection, AI, and malignancy following ALE in highly treatment refractory LT and short-term (ST) cohorts.
Methods: NCT01624714 Retrospective and prospective data collection of subjects in open label phase I clinical trial for treatment refractory MS. 61 subjects were followed for a mean 54 months (254 patient-years (PY)) post-ALE. Baseline median age was 49 (32-68) years. The LT cohort had a mean of 83 months follow up (FU), and ST had mean of 25 months FU.
Results: 41 SAE, nearly entirely hospitalization, occurred at a rate of 0.16 events per PY; only 1 for MS relapse. Serious events differed for LT 0.10/PY and ST 0.35/PY. Serious infections caused 16 hospitalizations (0.063/PY). Major infections included 4 opportunistic infections (fungal osteomyelitis 1, disseminated histoplasmosis 2, granulomatous fish handlers´ disease 1). Other infections included Urinary tract infection 3, 1 with paraparesis pseudorelapse; Pulmonary: pneumonia 2, pneumonia-sepsis 1; Gastroenteritis: C.difficile 1, Rotavirus gastroenteritis 1, fecal impaction with enteritis 1 and Other: post-operative MRSA osteomyelitis 1, and pseudofolliculitis 1. Serious infections also differed in rate between LT 0.04/PY and ST 0.1/PY. AI occurred, not usually requiring hospitalization: 5 Grave´s disease, 5 hypothyroidism, 2 goiter/nodule, 2 hemolytic anemias (HA), 1 ITP, 1 recurrent alopecia totalis. The total thyroid AI rate of 12/61 (20%) subjects or 0.047 events/PY. AI caused 4 hospitalizations (7% of subjects): thyrotoxicosis (2), ITP with mild pancytopenia and HA, and HA. AI rate was similar between the LT 0.061/PY and ST 0.08/PY. One HA resolved but recurrent infections after rituximab led to study withdrawal and death in hospice care. Malignancies other than basal cell carcinoma (BCC) did not occur, 3 BCC were excised (0.01 per PY).
Conclusions: Safety of ALE in this challenging and refractory cohort is similar to prior reports; AI, infections and hospitalizations occur. Histoplasmosis occurred multiple times in our cohort and is an endemic pathogen in our region. Serious infections may be higher than previously reported.
Disclosure: Funded in part by grant support from Sanofi-Genzyme to the Novel Pharmaceutics Institute, a 501(c)3 organization.
SFH receives research funding and honoraria from Sanofi-Genzyme.
DK receives honoraria and consulting payments from Sanofi-Genzyme.
MCM, SRS, RG, RM, LK, MB, JD have no relevant disclosures.
Abstract: P1182
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Anti-CD52 IgG ALE provides powerful, long-term (LT), disease-modifying effects with a liability for infusion-related, infectious, and autoimmune side effects; we present a large clinic cohort of highly treatment-refractory, older, higher disability subjects with LT data.
Objectives: Report complications of hospitalization, infection, AI, and malignancy following ALE in highly treatment refractory LT and short-term (ST) cohorts.
Methods: NCT01624714 Retrospective and prospective data collection of subjects in open label phase I clinical trial for treatment refractory MS. 61 subjects were followed for a mean 54 months (254 patient-years (PY)) post-ALE. Baseline median age was 49 (32-68) years. The LT cohort had a mean of 83 months follow up (FU), and ST had mean of 25 months FU.
Results: 41 SAE, nearly entirely hospitalization, occurred at a rate of 0.16 events per PY; only 1 for MS relapse. Serious events differed for LT 0.10/PY and ST 0.35/PY. Serious infections caused 16 hospitalizations (0.063/PY). Major infections included 4 opportunistic infections (fungal osteomyelitis 1, disseminated histoplasmosis 2, granulomatous fish handlers´ disease 1). Other infections included Urinary tract infection 3, 1 with paraparesis pseudorelapse; Pulmonary: pneumonia 2, pneumonia-sepsis 1; Gastroenteritis: C.difficile 1, Rotavirus gastroenteritis 1, fecal impaction with enteritis 1 and Other: post-operative MRSA osteomyelitis 1, and pseudofolliculitis 1. Serious infections also differed in rate between LT 0.04/PY and ST 0.1/PY. AI occurred, not usually requiring hospitalization: 5 Grave´s disease, 5 hypothyroidism, 2 goiter/nodule, 2 hemolytic anemias (HA), 1 ITP, 1 recurrent alopecia totalis. The total thyroid AI rate of 12/61 (20%) subjects or 0.047 events/PY. AI caused 4 hospitalizations (7% of subjects): thyrotoxicosis (2), ITP with mild pancytopenia and HA, and HA. AI rate was similar between the LT 0.061/PY and ST 0.08/PY. One HA resolved but recurrent infections after rituximab led to study withdrawal and death in hospice care. Malignancies other than basal cell carcinoma (BCC) did not occur, 3 BCC were excised (0.01 per PY).
Conclusions: Safety of ALE in this challenging and refractory cohort is similar to prior reports; AI, infections and hospitalizations occur. Histoplasmosis occurred multiple times in our cohort and is an endemic pathogen in our region. Serious infections may be higher than previously reported.
Disclosure: Funded in part by grant support from Sanofi-Genzyme to the Novel Pharmaceutics Institute, a 501(c)3 organization.
SFH receives research funding and honoraria from Sanofi-Genzyme.
DK receives honoraria and consulting payments from Sanofi-Genzyme.
MCM, SRS, RG, RM, LK, MB, JD have no relevant disclosures.