Ocrelizumab initiation in patients with MS: A multicenter observational study

Abstract

Objective: To provide first real-world experience on patients with MS treated with the B cell-depleting antibody ocrelizumab.

Methods: We retrospectively collected data of patients who had received at least 1 treatment cycle (2 infusions) of ocrelizumab at 3 large neurology centers. Patients' characteristics including premedication, clinical disease course, and documented side effects were analyzed.

Results: We could identify 210 patients (125 women, mean age ± SD, 42.1 ± 11.4 years) who had received ocrelizumab with a mean disease duration of 7.3 years and a median Expanded Disability Status Scale score of 3.75 (interquartile range 2.5-5.5; range 0-8). Twenty-six percent of these patients had a primary progressive MS (PPMS), whereas 74% had a relapsing-remitting (RRMS) or active secondary progressive (aSPMS) disease course. Twenty-four percent of all patients were treatment naive, whereas 76% had received immune therapies before. After ocrelizumab initiation (median follow-up was 200 days, range 30-1,674 days), 13% of patients with RRMS/aSPMS experienced a relapse (accounting for an annualized relapse rate of 0.17, 95% CI 0.10-0.24), and 5% of all patients with MS experienced a 12-week confirmed disability progression. Treatment was generally well tolerated, albeit only short-term side effects were recorded, including direct infusion-related reactions and mild infections.

Conclusions: We provide class IV evidence that treatment with ocrelizumab can stabilize naive and pretreated patients, indicating that ocrelizumab is an option following potent MS drugs such as natalizumab and fingolimod. Further studies are warranted to confirm these findings and to reveal safety concerns in the longer-term follow-up.

Classification of evidence: This study provides Class IV evidence that for patients with MS, ocrelizumab can stabilize both treatment-naive and previously treated patients.

Figure 1. Pretreatment before ocrelizumab initiation and clinical assessment during treatment-free interval (washout period)

(A) Twenty-four percent of patients were treatment naive, whereas 76% of patients had received a previous medication such as interferon-beta or natalizumab (number of patients treated with MS drug before ocrelizumab in (B). (C) Clinical disease course during the washout interval and length of washout interval for the depicted conditions. N (all) = 100 patients, n (natalizumab) = 32, n (fingolimod) = 17, and n (dimethyl fumarate) = 15. We observed significant higher washout intervals in patients who experienced a relapse (***p < 0.001, 1-way ANOVA, mean ± SEM); black symbols indicate stable patients and red symbols refer to patients with a relapse during the washout period. IVMPS = IV methylprednisolone every 3 months.

Figure 2. Clinical assessment after treatment initiation

(A) Overall, 15% of patients experienced a relapse (10%, n = 14) or 12-week confirmed disability progression (5%, n = 7) after ocrelizumab treatment initiation, with, e.g., 8% for natalizumab-pretreated patients (2 relapse/0 progression in 26 patients). N (all) = 136 patients, n (natalizumab) = 26, n (fingolimod) = 15, n (dimethyl fumarate) = 15, n (naive) = 31, n (PPMS) = 31, and n (RRMS) = 105. (B) Follow-up in days of the patients (mean ± SEM). (C) The mean occurrence of a relapse (n = 14 events) was 136 days after the first ocrelizumab infusion (mean ± SEM). Each point is labeled with the pretreatment. (D) Annualized relapse rate of our cohort compared with the ocrelizumab group and interferon beta-1a group of the OPERA 1 trial (mean with 95% CI). (E) Confirmed disability progression after 12 weeks of our cohort (mean with 95% CI). ALEM = alemtuzumab; DAC = daclizumab; DMF = dimethyl fumarate; FIN = fingolimod; GA = glatiramer acetate; IFN = interferon beta-1a; NAT = natalizumab; OCR = ocrelizumab; PPMS = primary progressive MS; RRMS = relapsing-remitting MS; TER = teriflunomide.