Serious Adverse Events, Autoimmunity, and Infections Following Alemtuzumab Therapy in a Large, High Disability, Treatment-Refractory MS Clinic Cohort
Objectives: Report rates of complications of hospitalization, infection, autoimmunity, and malignancy following ALE in highly treatment refractory long-term and short-term cohorts.
Methods: NCT01624714 Retrospective and prospective data collection of subjects in open label phase I clinical trial for treatment refractory MS. Total of 61 subjects were follow for a mean 54 months, or total of 254 patient-years (PY) post-ALE. Treatment was received at a median age of 49 (32-68) years. The long-term (LT) cohort had a mean of 83 months follow up (FU), and short-term (ST) mean of 25 months FU.
Results: 41 Serious adverse events, nearly entirely hospitalizations, 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: UTI (2), UTI with paraparesis pseudorelapse (1); Pulmonary: pneumonia (2), pneumonia and 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 long-term 0.04/PY and short-term 0.1/PY.
Autoimmunity occurred, not usually needing hospitalization: 5 Grave's disease, 5 hypothyroidism, 2 goiter/nodule, 2 hemolytic anemias, 1 ITP, 1 recurrent alopecia totalis. The total thyroid autoimmunity rate of 12/61 (20%) subjects or 0.047 events/PY. Autoimmunity caused 4 hospitalizations (7% of subjects), and were thyrotoxicosis (2), ITP with mild pancytopenia and hemolytic anemia, and hemolytic anemia. Autoimmunity rate was similar between the LT 0.061/PY and ST 0.08/PY. One anemia resolved but recurrent infections after rituximab led to study withdrawal, hospice care, and death.
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 previously reported, but infections and hospitalizations occur. Histoplasmosis occurred multiple times in our cohort and is an endemic pathogen in our region. Serious infection rate is likely higher than expected and weighted towards the first two years of treatment. Thyroid autoimmunity appears less common overall, judging from the thyroid complication rate over a very long follow up period.