Background

Ocrelizumab (OCR), an anti-CD20 antibody, was approved in the US in March 2017 for treating relapsing (RMS) and primary progressive MS (PPMS). Infections were more commonly seen in patients receiving OCR in earlier trials. Last year European Medicines Agency updated the OCR prescribing information to include the association between a reduction in immunoglobulins especially IgG and serious infections.

Objectives

To determine if there is a relationship in baseline and follow up immunoglobulins levels and the risk of having an infection

Methods

MS patients in our OCR registry with at least one IgM/IgG value and who received ≥2 doses of OCR were included. IgG/IgM levels were obtained within a month of each infusion. Wilcoxon rank-sum tests and linear models were used to examine the relationships between IgM/IgG and infections.

Results

337 patients were included. 72.4% were female; median age was 53.2 [IQR = 19.8] years with a median disease duration of 13.5 [IQR = 11.8] years. 78% had RMS, 13.4% had SPMS, and 8.6% had PPMS. 27% of patients were treatment naïve. Median time on OCR was 26 [IQR = 8.9] months. 88.7% of patients had more than one IgG and IgM value. Infections were seen in 226 (67.1%) patients. The median age of patients who did and did not have an infection was 53.5 [IQR =20.2] and 53 [IQR = 18.1] respectively. Prior natalizumab use was associated with a higher rate of infection, 46 of 62 (74%). No significant differences were found between IgM levels nor IgG levels for cases of infection (56 [IQR = 53], 792 [IQR = 294.5] mg/dL) and non-infection (52 [IQR = 51], 828.5 [IQR = 310.2]) mg/dL) (

Conclusions

Older patients with longer duration of disease and OCR therapy have been found to have more infections, but we did not observe age as a risk factor for infection in this cohort. Furthermore, neither baseline nor follow up IgM or IgG levels predicted infections in this study. However, the median time on OCR was a little over 2 years which may be too soon to see a difference in the rate of infection and immunoglobulin levels.

Background

Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, was approved in the US in 2017 for the treatment of relapsing MS (RMS) and primary progressive MS (PPMS). The Providence OCR Registry (POR) was established to monitor long-term treatment and safety outcomes.

Objectives

To evaluate OCR treatment outcomes including clinical and radiographic changes as well as safety issues using real-world data from a diverse, community-based MS population.

Methods

Adult MS patients who have been prescribed OCR were eligible. Chart reviews at OCR start date and every 6 months thereafter were done by a trained RN. Expanded Disability Status Scale (EDSS) scores were determined by the treating provider on the start date and then yearly. Descriptive statistics and paired t-tests were used.

Results

Of the 355 patients enrolled from March 2017 to March 2020, 71.9% were female; mean (SD) age was 51.8 (12.5) years; 78.3% had RMS, 13.2% had SPMS, and 8.5% had PPMS. Median baseline EDSS [interquartile range (IQR)] was 3.0 [2.0, 4.0], 6.5 [6.0, 7.5], and 6.5 [6.0, 7.0] respectively. The RMS cohort had an annualized relapse rate (ARR) of 0.34 prior to starting OCR. Among all patients who had > 1 dose of OCR (n=332), ARR was 0.09 with 4 patients having 2 relapses and 1 patient having 3 relapses. Median EDSS scores at 12 months were 3.0 [2.0, 5.5] (n=151) for RMS patients, 6.5 [6.5, 7.5] (n=31) for SPMS, and 6.5 [5.6, 7.5] (n=16) for PPMS. Infusion reactions occurred in 32.9% of patients during dose one, becoming less frequent with subsequent doses. Respiratory infections occurred in 40.1% of patients followed by urinary tract infections (UTI) (33.1%). Of 34 patients hospitalized, 11 patients had multiple hospitalizations. 25 hospitalizations were due to infections, 14 (56%) of which were due to UTIs. Sixty-five percent of these patients were 55 years or older. Forty-three (12.0%) patients have stopped OCR with a median time to discontinuation [IQR] of 10.8 [6.1,18.9] months; 24 patients stopped due to side effects, 15 patients stopped due to a relapse or clinical progression, and four patients died one each due to septic shock from pneumonia, urosepsis, suicide, and respiratory distress. There were no significant changes in Beck Depression Inventory (BDI), but 87 patients who had baseline and 12 month Modified Fatigue Inventory (MFIS), had significant improvement at 12 months (mean difference -3.7 (±14.1), (p=0.02).

Conclusions

Our study showed that OCR was effective in controlling relapse and disability worsening and reported similar rates of infusion reactions compared to earlier phase III clinical trials. Although only a small percentage of patients have stopped OCR, infections resulting in hospitalization are a concern, especially in older patients.

Background

The management of GI symptoms associated with the initiation of DMF has evolved over time with real world experience. The combined effect of GI management strategies has not been assessed in randomized studies and their overall impact on the incidence of GI symptoms and therapy discontinuation due to GI events is currently unclear.

Objectives

To compare discontinuation rate due to gastrointestinal (GI) symptoms in the first year after initiating dimethyl fumarate (DMF) between an early (post launch) and recent DMF cohort of multiple sclerosis (MS) patients at two MS centers.

Methods

Data were collected through chart reviews at Rocky Mountain MS Center and Providence MS Center. The cutoff for Early versus Recent cohort was April 1, 2014. Chi-square, non-parametric, and t-tests were used to determine differences between the two cohorts. Differences in discontinuation due to a GI event for the two cohorts were compared with a Cox proportional hazards model adjusted for baseline characteristics.

Results

Medical records of 700 patients who initiated DMF between March 2013 and December 2017 were reviewed- 302 were Early and 398 Recent. At baseline, Early patients were older (50.30 vs 48.50, p=0.049), had longer disease duration [11.09 (IQR: 7.88, 16.77) vs 6.72 (4.35, 13.72), p<0.001], more history of GI disease (27.8% vs. 22.1%, p=0.099) but lower percent of seasonal allergy (17.9 vs. 24.4, p=0.048). Discontinuation for any reason was higher in Recent patients (37.4% vs. 22.2%, p<0.001). Discontinuation due to GI symptom were 8.6% in the Early patients and 12.1% in the Recent patients (p=0.178). Females [HR: 2.27 (1.12-4.60)] and patients with a history of GI condition [HR: 2.14, (1.32-3.47)] were more likely to discontinue. No significant associations were found between discontinuation and any GI events or previous exposure to natalizumab or other medications. None of the baseline or patient characteristics were found to be risk factor of GI events except study site.

Conclusions

Overall, the discontinuation rate due to GI symptoms was no different between the Early and Recent patient cohorts. However, the odds of having a GI symptom at the Rocky Mountain site were higher although discontinuation for this site was lower suggesting there may be differences in symptom reporting, data abstraction, and GI mitigation strategies between the two centers. Further research with prospective study design and standard documentation and data abstraction tool are needed.

Support: Biogen