ABSTRACT
BACKGROUND: Ocrelizumab is an effective anti-CD20 therapy approved for Relapsing Remitting (RRMS) and Primary Progressive Multiple Sclerosis (PPMS). In clinical trials, a proportion of patients developed hypogammaglobulinemia which could contribute to infection risk. This study aimed to identify hypogammaglobulinemia and its risk factors and evaluate potentially associated serious infection risk in a real-world cohort of patients. METHODS: All MS patients treated with ocrelizumab in a Quebec City MS clinic from January 2017 to August 2021 were included and detailed patient characteristics were collected by chart review. Levels of immunoglobulins (IgM, IgA and IgG) were assessed prior to each treatment. Serious infection was defined as an infection requiring hospitalization or emergency room treatment. Association between hypogammaglobulinemia and serious infection was analyzed. RESULTS: A total of 266 patients (average follow-up 2.05 years) were included (87% RRMS). After 6 infusions, 32.8%, 3.5% and 4.2% of patients had at least one IgM, IgA and IgG hypogammaglobulinemia event respectively. Aside from pre-treatment hypogammaglobulinemia, there were no variables associated with on-treatment hypogammaglobulinemia. There was a total of 21 serious infections (3.36 and 12.33 per 100-person-years in RRMS and PPMS). Developing hypogammaglobulinemia during treatment was not associated with serious infection. A regression analysis did not show associations between serious infection and key disease characteristics. CONCLUSION: Similar to ocrelizumab extension studies, our cohort demonstrated a significant rate of hypogammaglobulinemia over time, mostly with IgM. No association was found between hypogammaglobulinemia and serious infection.
ABSTRACT
OBJECTIVEThe aim of this study was to derive a clinically applicable decision rule using clinical, radiological, and laboratory data to predict the development of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients.METHODSPatients presenting over a consecutive 9-year period with subarachnoid hemorrhage (SAH) and at least 1 angiographically evident aneurysm were included. Variables significantly associated with DCI in univariate analysis underwent multivariable logistic regression. Using the beta coefficients, points were assigned to each predictor to establish a scoring system with estimated risks. DCI was defined as neurological deterioration attributable to arterial narrowing detected by transcranial Doppler ultrasonography, CT angiography, MR angiography, or catheter angiography, after exclusion of competing diagnoses.RESULTSOf 463 patients, 58% experienced angiographic vasospasm with an overall DCI incidence of 21%. Age, modified Fisher grade, and ruptured aneurysm location were significantly associated with DCI. This combination of predictors had a greater area under the receiver operating characteristic curve than the modified Fisher grade alone (0.73 [95% CI 0.67-0.78] vs 0.66 [95% CI 0.60-0.71]). Patients 70 years or older with modified Fisher grade 0 or 1 SAH and a posterior circulation aneurysm had the lowest risk of DCI at 1.2% (0 points). The highest estimated risk was 38% (17 points) in patients 40-59 years old with modified Fisher grade 4 SAH following rupture of an anterior circulation aneurysm.CONCLUSIONSAmong patients presenting with aSAH, this score-based clinical prediction tool exhibits increased accuracy over the modified Fisher grade alone and may serve as a useful tool to individualize DCI risk.
