| Coverage Policy Manual | |
| Policy #: | 2017021 |
| Category: | Pharmacy |
| Initiated: | June 2017 |
| Last Review: | December 2023 |
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| Ocrelizumab (e.g., Ocrevus) | |
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| Description: |
Ocrelizumab is a recombinant human anti-CD20 (a B-cell marker) monoclonal antibody that binds to CD20 epitope (different than but overlaps with rituximab). Modification of the Fc region enhances antibody-dependent cell-mediated cytotoxicity and reduces complement-dependent cytotoxicity optimizing B cell depletion compared with rituximab. Evidence from randomized trials shows that ocrelizumab is more effective than interferon beta-1a for reducing relapses and may slow disability progression in primary progressive multiple sclerosis (PPMS).
Ocrelizumab is contraindicated in patients with active hepatitis B virus infection. Patients must be screened for hepatitis B virus before starting ocrelizumab. Patients should receive all necessary immunizations at least six weeks prior to starting ocrelizumab; live-attenuated and live vaccines are not recommended during ocrelizumab treatment or after discontinuation until B-cell repletion occurs.
There are no data regarding the risk of fetal harm associated with ocrelizumab treatment for pregnant women, but animal data suggest harm with observations of increased perinatal mortality and renal, bone marrow, and testicular toxicity.
Regulatory Status
On March 28, 2017, the U.S. Food and Drug Administration approved Ocrelizumab (e.g., Ocrevus) for the treatment of adult patients with relapsing or primary progressive forms of multiple sclerosis.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
Effective April 15, 2023, prior approval is required for Ocrelizumab (e.g. Ocrevus).
Effective December 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
Ocrelizumab meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of primary progressive multiple sclerosis (PPMS) or relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, provided ALL the following criteria are met (FDA, 2021):
CONTINUED APPROVAL for up to 1 year:
Dosage and Administration
Dosing per FDA Guidelines
NOTE: Per FDA label, counseling regarding avoidance of vaccination with live virus vaccines (FDA 2021) and increased risk of malignancy with use of ocrelizumab (FDA, 2021) is recommended
The recommended dosing of ocrelizumab is 300 mg IV every 2 weeks for the first two doses, followed by 600 mg every 6 months.
Ocrelizumab is available as an injection: 300 mg/10 mL (30 mg/mL) in a single-dose vial.
Ocrelizumab should be administered by a healthcare professional.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Ocrelizumab, for any indication or circumstance not described above, does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For member with contracts without primary coverage criteria, ocrelizumab, for any indication or circumstance not described above, is considered investigational.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective September 1, 2023 to November 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Ocrelizumab meets primary coverage criteria that there be scientific evidence of effectiveness for the treatment of primary progressive multiple sclerosis (PPMS) or relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, provided all the following criteria are met (FDA, 2021):
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 1 year:
Dosage and Administration
Dosing per FDA Guidelines
NOTE: Per FDA label, counseling regarding avoidance of vaccination with live virus vaccines (FDA 2021) and increased risk of malignancy with use of ocrelizumab (FDA, 2021) is recommended
The recommended dosing of ocrelizumab is 300mg IV every 2 weeks for the first two doses, followed by 600mg every 6 months.
Ocrelizumab is available as an injection: 300 mg/10 mL (30 mg/mL) in a single-dose vial.
Ocrelizumab should be administered by a healthcare professional.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Ocrelizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for the following:
For member with contracts without primary coverage criteria, ocrelizumab is considered investigational including the following:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective January 2023 to October 31, 2023
Effective April 15, 2023, prior approval is required for Ocrelizumab (e.g. Ocrevus)
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of ocrelizumab meets primary coverage criteria that there be scientific evidence of effectiveness for the treatment of primary progressive multiple sclerosis (PPMS) or relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, provided all the following criteria are met (FDA, 2021):
Dosage and Administration
NOTE: Per FDA label, counseling regarding avoidance of vaccination with live virus vaccines (FDA 2021) and increased risk of malignancy with use of ocrelizumab (FDA, 2021) is recommended
Dosing per FDA Guidelines
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 300mg IV every 2 weeks for the first two doses, followed by 600mg every 6 months.
Ocrelizumab is available as an injection: 300 mg/10 mL (30 mg/mL) in a single-dose vial.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of ocrelizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for the following:
For member with contracts without primary coverage criteria, ocrelizumab is considered investigational including the following:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective January 2022
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of ocrelizumab meets primary coverage criteria that there be scientific evidence of effectiveness for the treatment of primary progressive multiple sclerosis (PPMS) or relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, provided all of the following criteria are met (FDA, 2021):
Dosage and Administration
Dosing per FDA Guidelines
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 300mg IV every 2 weeks for the first two doses, followed by 600mg every 6 months.
Ocrelizumab is available as an injection: 300 mg/10 mL (30 mg/mL) in a single-dose vial.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of ocrelizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for the following:
For member with contracts without primary coverage criteria, ocrelizumab is considered investigational including the following:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective December 2019 - January 2022
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of ocrelizumab meets primary coverage criteria that there be scientific evidence of effectiveness for the treatment of primary progressive multiple sclerosis (PPMS) or relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease provided all of the following criteria are met:
Dosing
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of ocrelizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for the following:
For member with contracts without primary coverage criteria, ocrelizumab is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective April 2019 to November 2019
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of ocrelizumab meets primary coverage criteria for the treatment of primary progressive multiple sclerosis (PPMS) or relapsing remitting multiple sclerosis (RRMS) provided all of the following criteria are met:
Dosing:
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of ocrelizumab does not meet primary coverage criteria and for members with contracts without primary coverage criteria is considered investigational for the following:
For members with contracts without primary coverage criteria, the use of natalizumab for all other indications and conditions, including but not limited to the above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
EFFECTIVE March 2019
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of ocrelizumab meets primary coverage criteria for the treatment of a) primary progressive multiple sclerosis (PPMS) and b) treatment of relapsing remitting multiple sclerosis (RRMS) that has failed treatment with at least one other approved therapy for RRMS provided all of the following criteria are met:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of ocrelizumab does not meet primary coverage criteria and for members with contracts without primary coverage criteria is considered investigational for the following:
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Dosing:
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 300mg every 2 weeks for the first two doses, followed by 600mg every 6 months.
Ocrelizumab is given as an IV infusion.
EFFECTIVE SEPTEMBER 2017 to February 2019
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of ocrelizumab meets primary coverage criteria for the treatment of a) primary progressive multiple sclerosis (PPMS) and b) treatment of relapsing remitting multiple sclerosis (RRMS) that has failed treatment with at least one other approved therapy for RRMS provided all of the following criteria are met:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of ocrelizumab does not meet primary coverage criteria and for members with contracts without primary coverage criteria is considered investigational for the following:
Dosing:
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 300mg every 2 weeks for the first two doses, followed by 600mg every 6 months.
Ocrelizumab is given as an IV infusion.
EFFECTIVE PRIOR TO SEPTEMBER 2017
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of ocrelizumab for the treatment of primary progressive multiple sclerosis (PPMS) meets coverage criteria provided all of the following criteria are met:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of ocrelizumab does not meet primary coverage criteria and for members with contracts without primary coverage criteria is considered investigational for the following:
Dosing:
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 300mg every 2 weeks for the first two doses, followed by 600mg every 6 months.
Ocrelizumab is given as an IV infusion.
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| Rationale: |
Primary Progressive Multiple Sclerosis (PPMS)
The efficacy and safety of ocrelizumab in primary progressive multiple sclerosis was assessed in a double-blind, placebo-controlled clinical trial in which 732 patients were randomized 2:1 to receive either ocrelizumab (n=488) or placebo (n=244) (Montalban, 2017). Inclusion criteria included a baseline EDSS of 3 to 6.5 and a score of 2 or greater for the EDSS pyramidal functional system due to lower extremity findings. The primary outcome was the time to onset of disability progression attributable to MS confirmed to be present at least 12 weeks later at the next neurological assessment. Disability progression was defined as an EDSS score increase by 1 point or more from baseline if the baseline EDSS score was 5.5 or less, or an EDSS score increase by 0.5 points if the baseline EDSS score was more than 5.5 points. Timed 25-foot walk and percentage change in T2 hyperintense lesion volume were also measured. Proportion of patients with 12-week confirmed disability progression was 32.9% in the ocrelizumab group and 39.3% in the placebo group (P=.0321). The mean change in volume of T2 lesions from baseline to week 120 was -0.39 cm3 for ocrelizumab and 0.79 cm3 for the placebo group (p<0.0001). The most common adverse reactions were upper respiratory tract infections (49% ocrelizumab group versus 43% placebo group), infusion reactions (40% ocrelizumab group versus 26% placebo group), skin infections (14% ocrelizumab group versus 11% placebo group), and lower respiratory tract infections (10% ocrelizumab group versus 9% placebo group). Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo.
Relapsing Remitting Multiple Sclerosis (RRMS)
Two identical randomized, controlled trials (OPERA I and OPERA II) of 821 and 825 adults with relapsing multiple sclerosis compared intravenous ocrelizumab (600 mg every 24 weeks) with subcutaneous interferon beta-1a (44 mcg three times weekly) for 96 weeks (Hauser, 2017). All patients were pretreated with one dose of intravenous methylprednisolone (100 mg) before each infusion. The following observations were reported:
●An earlier phase 2 randomized trial of over 200 patients with RRMS demonstrated that ocrelizumab, compared with placebo, reduced the appearance of gadolinium-enhancing brain lesions on MRI by approximately 90 percent and reduced the annualized relapse rate by 70 to 80 percent [81]. In addition, ocrelizumab was better than interferon beta-1a for reducing the appearance of new gadolinium-enhancing lesions on brain MRI and the annualized relapse rate.
No comparative studies with RRMS therapies—other than beta-interferon—are found. The role of this agent in the treatment of RRMS remains unclear pending comparative studies with other approved RRMS agents and further safety data on rates of neoplasms and infection.
Rheumatoid Arthritis
In an analysis of the double-blind, placebo-controlled periods and long-term follow-up of 4 OCR phase III trials in RA (SCRIPT, STAGE, FILM and FEATURE) (Emery, 2014). Safety data per study and the results of a meta-analysis of serious infectious events (SIEs) including the following:
Overall, 868 patients received placebo, 1064 patients OCR 200 mg×2 (or 400 mg×1) (OCR200), and 827 patients OCR 500 mg×2 (OCR500) plus background methotrexate (MTX) at baseline and 24 weeks. During the double-blind, placebo-controlled periods, the incidence of adverse events and serious adverse events was comparable between the OCR+MTX and placebo +MTX groups. Infusion-related reactions were more common with OCR+MTX and decreased in frequency with subsequent infusions. Serious infusion-related reactions were rare (0.1%). Serious infections occurred more frequently with OCR500+MTX. In the meta-analysis, a statistically significant difference from placebo +MTX in incidence of SIEs per 100 patient-years of 2.4 (95% CI, 0.3–4.5) was observed with OCR500+MTX, but not with OCR200+MTX (0.6; 95% CI, −1.3 to 2.4). Patients recruited in Asia exhibited a higher risk of serious infections (hazard ratio, 1.78; 95% CI, 1.03–3.06). The incidence of human anti-human antibodies was <5%. Long-term follow-up indicated no differences in malignancy rates between the treatment groups. There was no apparent difference in time to B-cell repletion between the OCR dose groups
In placebo-controlled clinical trials of RA, OCR500+MTX was associated with a higher risk of serious infections compared with placebo +MTX. The safety profile of OCR 200+MTX was comparable with placebo+MTX.
Lupus Nephritis
A comparative trial to investigate the efficacy and safety of ocrelizumab in patients with class III/IV lupus nephritis (LN) was published (Mysler, 2013) as summarized below:
Patients were randomized 1:1:1 to receive placebo, 400 mg ocrelizumab, or 1,000 mg ocrelizumab given as an intravenous infusion on days 1 and 15, followed by a single infusion at week 16 and every 16 weeks thereafter, accompanied by background glucocorticoids plus either mycophenolate mofetil (MMF) or the Euro-Lupus Nephritis Trial (ELNT) regimen (cyclophosphamide followed by azathioprine). The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated patients versus placebo-treated patients. We report week 48 efficacy data for patients receiving ≥32 weeks of treatment (n = 223) and safety results for all treated patients (n = 378).
The overall renal response rate was 54.7%, 66.7%, 67.1%, and 66.9% in the placebo-treated, 400 mg ocrelizumab–treated, 1,000 mg ocrelizumab–treated, and combined ocrelizumab-treated groups, respectively. The associated treatment difference versus placebo for the combined ocrelizumab-treated groups was 12.7% (95% confidence interval [95% CI] −0.8, 26.1) (P = 0.065), with similar differences observed for both ocrelizumab-treated groups. Ocrelizumab versus placebo treatment differences were apparent in patients receiving the background ELNT regimen, but not in those receiving background MMF. A numerically greater proportion of ocrelizumab-treated patients had a ≥50% reduction in the urinary protein:urinary creatinine ratio at 48 weeks compared with placebo-treated patients (placebo-treated patients, 58.7%; 400 mg ocrelizumab–treated patients, 70.7%; 1,000 mg ocrelizumab–treated patients, 68.5%). Serious adverse events occurred in 27.2% of placebo-treated patients, 35.7% of 400 mg ocrelizumab–treated patients, and 22.0% of 1,000 mg ocrelizumab–treated patients. Corresponding serious infection rates (events/100 patient-years) were 18.7 (95% CI 12.2, 28.7), 28.8 (95% CI 20.6, 40.3), and 25.1 (95% CI 17.4, 36.1), respectively. The imbalance in serious infections with ocrelizumab occurred with background MMF but not with the background ELNT regimen.
In patients with active LN, overall renal response rates with ocrelizumab were numerically but not statistically significantly superior to those with placebo. Ocrelizumab treatment was associated with a higher rate of serious infections in the subgroup receiving background MMF.
2018 Update
A literature search conducted through December 2018 did not reveal any new information that would prompt a change in the coverage statement.
December 2019 Update
Multiple Sclerosis is an inflammatory and neurodegenerative disease of the central nervous system, and both T and B cells are involved in its pathogenesis. The vast majority of disease-modifying drugs used for MS act on the inflammatory component of the disease and are approved for use in relapsing-remitting (RR) patients. Ocrelizumab has been approved by the US Food and Drug Administration not only for patients with RRMS but also for patients with primary progressive MS. OCR is a humanized anti-CD20 monoclonal antibody that can deplete the targeted B cells through antibody-dependent cellular cytotoxicity. Treatment involves administration by intravenous infusion every 6 months. OCR can cause long-lasting B-cell depletion and change the pool of reconstituted B cells. Phase III clinical trials have confirmed the results of previous Phase II studies. In particular, OPERA I and II trials, which were performed in patients with RRMS, showed a reduction in the annualized relapse rate, the risk of disability progression, and the number of new/enlarging T2 lesions and enhancing lesions measured using brain magnetic resonance. The ORATORIO trial, performed in PP subjects, showed that OCR can reduce disability progression, improve performance on the timed 25-foot walk, and decrease the total volume of T2 lesions and the mean number of new or enlarging T2 lesions. The most frequent adverse events were the infusion-related reactions and infections. Infections were mostly nasopharyngitis, as well as upper respiratory and urinary tract infections. OCR gives no indication for severe or opportunistic infections. There is not a clear increased risk of malignancies. Nevertheless, it could not be excluded. Real-life registries will provide more information about the long-term safety, the risk of exposure during pregnancy, and the risk of rare adverse events. In this review, the evidence was analyzed regarding the efficacy and the safety of OCR.
All clinical trials comparing OCR versus placebo or interferon beta have shown the superiority of this monoclonal antibody in many clinical and neuroimaging aspects. These studies are important for patients with RRMS, as these present a new therapeutic option. However, OCR is even more important for PPMS subjects, as it is the first drug to be approved for use in patients with this phenotype of MS. Given the strict inclusion criteria in the Phase III trial for patients with PPMS, the generalization of OCR treatment usefulness to patients without these features needs further clarification. Moreover, in both PP and RR patients, the impact of OCR in reducing the progression of brain atrophy was very small, and this result once again suggests that its prevalent action is on the inflammatory aspect of the disease, rather than on neurodegeneration itself.
December 2020 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2020. No new literature was identified that would prompt a change in the coverage statement.
2021 Update
A randomized, parallel, placebo‐controlled Phase II study (NCT00676715) in patients with relapsing–remitting MS (RRMS) demonstrated that ocrelizumab is highly efficacious and well tolerated, with pronounced effects on magnetic resonance imaging and relapse‐related outcomes. Two identical, pivotal Phase III studies in patients with RMS, OPERA I (NCT01247324) and OPERA II (NCT01412333), demonstrated the superiority of ocrelizumab 600 mg IV every 6 months over interferon β‐1a on relapse rate, confirmed disability progression, and brain lesion activity over the 2‐year controlled treatment period. In a Phase III study in patients with PPMS, ORATORIO (NCT01194570), ocrelizumab 600 mg IV every 6 months reduced the risk of confirmed disability progression compared with placebo and was superior on other measures of disease progression including the time required to walk 25 feet, the volume of chronic brain lesions and brain volume loss. Based on the outcomes of these pivotal studies, ocrelizumab 600 mg IV every 6 months is indicated for the treatment of RMS and PPMS. (Gibiansky E, Petry C, Mercier F, et.al., 2020)
October 2022 Update
A prospective cohort study in patients with MS receiving ocrelizumab ≥1 year was conducted. Most participants received B-cell guided personalized extended interval dosing to limit ocrelizumab exposure and hospital visits during the COVID-19 pandemic (cut-off ≥ 10 cells/µL). Participants completed questionnaires during ocrelizumab infusion and 2 weeks thereafter. Demographics, clinical and radiological characteristics, CD19 B-cell counts, and serum neurofilament light (sNfL) levels were collected. Data were analyzed using logistic regression analyses.
Seventy-one (61%) out of 117 participants reported the wearing-off phenomenon during ocrelizumab treatment. The most frequently reported symptoms were fatigue, cognitive disability and sensory symptoms. Wearing-off symptoms started < 1 week (11%), 1-4 weeks (49%) or more than 4 weeks (37%) before ocrelizumab infusion. Fifty participants (43%) reported a current wearing-off phenomenon at the first questionnaire. Higher body mass index (threshold BMI ≥ 25) increased the odds of reporting a current wearing-off phenomenon (OR 2.70, 95% CI 1.26 to 5.80, p = .011). Infusion interval, EDSS score, MRI disease activity, clinical relapses, CD19 B-cell counts, and sNfL levels were no predictors. Disappearance of the wearing-off phenomenon occurred in the first week after ocrelizumab infusion in most participants. Participants with a current wearing-off phenomenon significantly improved in self-reported physical and psychological functioning after ocrelizumab infusion. Reporting the wearing-off phenomenon did not influence treatment satisfaction. Forty of 109 participants (37%) reported post-infusion symptoms, such as fatigue, flu-like symptoms or walking difficulties. These post-infusion symptoms started directly or in the first week after ocrelizumab infusion and disappeared within 2 weeks.
The wearing-off phenomenon is reported by more than half of patients with MS using ocrelizumab. Only BMI was identified as a predicting factor. The wearing-off phenomenon was not elicited by extending infusion intervals or higher B-cell counts. The wearing-off phenomenon of ocrelizumab therefore does not seem to reflect suboptimal control of MS disease activity. (Toorop AA, van Lierop ZYGJ, Strijbis EMM, et.al., 2021)
2022 Update
CASTING was a prospective, international, multicenter, single-arm, open-label phase 3 trial (NCT02861014). Patients (Expanded Disability Status Scale [EDSS] score ≤ 4.0, with discontinued prior DMT of ≥6 months duration due to suboptimal disease control) received intravenous ocrelizumab 600 mg every 24 weeks for 96 weeks. The primary endpoint was NEDA (defined as absence of relapses, disability progression, and inflammatory MRI measures, with prespecified MRI re-baselining at Week 8) over 96 weeks.
A total of 680 patients were enrolled, 167 (24.6%) based on MRI activity only. At Week 96, 74.8% (95% confidence interval [CI] 71.3-78.0, n/N = 492/658) of patients had NEDA. NEDA was highest among patients enrolled due to MRI activity alone (80.6% [95% CI 68.6-89.6], n/N = 50/62) versus those enrolled for relapse (75.1% [95% CI 69.0-80.6], n/N = 172/229) or for relapse with MRI (70.5% [95% CI 60.0-79.0], n/N = 74/105). NEDA across subgroups was highest in patients with a baseline EDSS score <2.5 (77.2% [95% CI 72.8-81.2], n/N = 315/408). NEDA was higher in patients receiving one prior DMT (77.6% [95% CI 73.2-81.6], n/N = 312/402) versus two prior DMTs (70.3% [95% CI 64.3-75.8], n/N = 180/256).
In patients switching therapy due to suboptimal disease control, treatment with ocrelizumab led to an overall high NEDA rate across a wide range of disease-related and demographic subgroups, regardless of prior treatment background, with no new safety signals detected. (Vermersch P, Oreja-Guevara C, Siva A, et.al., 2021)
2023 Update
Patients in OPERA I/II and ORATORIO were grouped in exposure quartiles based on their observed individual serum ocrelizumab level over the treatment period. Exposure-response relationships were analyzed for clinical efficacy (24-week confirmed disability progression (CDP), annualized relapse rate [ARR], and MRI outcomes) and adverse events.
Ocrelizumab reduced new MRI lesion counts to nearly undetectable levels in patients with relapsing or primary progressive MS across all exposure subgroups, and reduced ARR in patients with relapsing MS to very low levels (0.13-0.18). A consistent trend of higher ocrelizumab exposure leading to lower rates of CDP was seen (0%-25% [lowest] to 75%-100% [highest] quartile hazard ratios and 95% confidence intervals; relapsing MS: 0.70 [0.41-1.19], 0.85 [0.52-1.39], 0.47 [0.25-0.87], and 0.34 [0.17-0.70] vs interferon β-1a; primary progressive MS: 0.88 [0.59-1.30], 0.86 [0.60-1.25], 0.77 [0.52-1.14], and 0.55 [0.36-0.83] vs placebo). Infusion-related reactions, serious adverse events, and serious infections were similar across exposure subgroups. (Hauser SL, Bar-Or A, Weber MS, 2023)
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| References: |
Emery P, Rigby W, Tak PP et al.(2014) Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. PLoS One. 2014; 9(2) e87379. Frau J, Coghe G, Lorefice L, Fenu G, Cocco E.(2018) New horizons for multiple sclerosis therapeutics: milestones in the development of ocrelizumab. Neuropsychiatr Dis Treat. 2018;14:1093–1099. Published 2018 Apr 23. doi:10.2147/NDT.S147874 Gibiansky E, Petry C, Mercier F, Günther A, Herman A, Kappos L, Hauser S, Yamamoto Y, Wang Q, Model F, Kletzl H.(2020) Ocrelizumab in relapsing and primary progressive multiple sclerosis: Pharmacokinetic and pharmacodynamic analyses of OPERA I, OPERA II and ORATORIO. Br J Clin Pharmacol. 2021 Jun;87(6):2511-2520. doi: 10.1111/bcp.14658. Epub 2020 Dec 7. PMID: 33202059; PMCID: PMC8247316. Hauser SL, Bar-or A, Comi G, et al.(2017) Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017;376(3):221-234. Hauser SL, Bar-Or A, Weber MS, Kletzl H, Günther A, Manfrini M, Model F, Mercier F, Petry C, Wing Q, Koendgen H, Smith T, Kappos L.(2023) Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Feb 15;10(2):e200094. doi: 10.1212/NXI.0000000000200094. Erratum in: Neurol Neuroimmunol Neuroinflamm. 2023 Mar 27;10(3): PMID: 36792367; PMCID: PMC9931184. Montalban X, Hauser SL, Kappos L, et al.(2017) Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209-220. Mysler EF, Spindler AJ, Guzman R, et al.(2013) Efficacy and safety of ocrelizumab in active proliferative lupus nephritis: results from a randomized, double-blind, phase III study. Arthritis & Rheumatism. 2013. 65 (9): 2368-2379. Doi:10.1002/art.38037. Ocrelizumab [Internet]. Elsevier. c2017- [cited 2017 April 24]. Available from: http://www.clinicalpharmacology.com Ocrevus® [package insert]. San Francisco, CA: Genentech, Inc.; 2017 Ocrevus®(2021) [package insert]. San Francisco, CA: Genentech, Inc.; 2021 Ocrevus®(2022) [package insert]. San Francisco, CA: Genentech, Inc.; 2022 Toorop AA, van Lierop ZYGJ, Strijbis EMM, Teunissen CE, Barkhof F, Uitdehaag BMJ, van Kempen ZLE, Killestein J.(2021) The wearing-off phenomenon of ocrelizumab in patients with multiple sclerosis. Mult Scler Relat Disord. 2022 Jan;57:103364. doi: 10.1016/j.msard.2021.103364. Epub 2021 Nov 1. PMID: 35158470. Vermersch P, Oreja-Guevara C, Siva A, Van Wijmeersch B, Wiendl H, Wuerfel J, Buffels R, Kadner K, Kuenzel T, Comi G; CASTING Investigators.(2022) Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis with suboptimal response to prior disease-modifying therapies: A primary analysis from the phase 3b CASTING single-arm, open-label trial. Eur J Neurol. 2022 Mar;29(3):790-801. doi: 10.1111/ene.15171. Epub 2021 Nov 25. PMID: 34748672; PMCID: PMC9299209. |
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Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association. |
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