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Lowering rituximab dose in patients with MS proves safe and effective
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
FROM MULTIPLE SCLEROSIS JOURNAL
Lower urinary tract dysfunction in patients with MS
Key clinical point: Higher Expanded Disability Status Scale (EDSS) score is associated with an unfavorable urologic course in patients with multiple sclerosis (MS), and increased postvoid residual volume (PVR) correlates with male gender, EDSS, and disease course.
Major finding: The presence of lower urinary tract symptoms (LUTS) was more frequently associated with a primary progressive disease course (P = .040), a higher level of disability (mean EDSS of 6.4, P = .011), and urinary tract infection (P = .002). PVR values were higher in patients with LUTS vs. those without (P = .011). Increased PVR correlated with male gender (P less than .001), EDSS score (P = .005), and disease course (P = .041). Higher PVR correlated with incontinence (P = .007), chronic urinary retention (P less than .001), incomplete emptying (P = .015), and diminished stream intensity (P = .040).
Study details: The findings are based on a study of 501 patients with clinically definite MS (68.9% females; mean age: 56.0 ± 12.3 years).
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Monti Bragadin M et al. Mult Scler Relat Disord. 2020 Jul 5. doi: 10.1016/j.msard.2020.102378.
Key clinical point: Higher Expanded Disability Status Scale (EDSS) score is associated with an unfavorable urologic course in patients with multiple sclerosis (MS), and increased postvoid residual volume (PVR) correlates with male gender, EDSS, and disease course.
Major finding: The presence of lower urinary tract symptoms (LUTS) was more frequently associated with a primary progressive disease course (P = .040), a higher level of disability (mean EDSS of 6.4, P = .011), and urinary tract infection (P = .002). PVR values were higher in patients with LUTS vs. those without (P = .011). Increased PVR correlated with male gender (P less than .001), EDSS score (P = .005), and disease course (P = .041). Higher PVR correlated with incontinence (P = .007), chronic urinary retention (P less than .001), incomplete emptying (P = .015), and diminished stream intensity (P = .040).
Study details: The findings are based on a study of 501 patients with clinically definite MS (68.9% females; mean age: 56.0 ± 12.3 years).
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Monti Bragadin M et al. Mult Scler Relat Disord. 2020 Jul 5. doi: 10.1016/j.msard.2020.102378.
Key clinical point: Higher Expanded Disability Status Scale (EDSS) score is associated with an unfavorable urologic course in patients with multiple sclerosis (MS), and increased postvoid residual volume (PVR) correlates with male gender, EDSS, and disease course.
Major finding: The presence of lower urinary tract symptoms (LUTS) was more frequently associated with a primary progressive disease course (P = .040), a higher level of disability (mean EDSS of 6.4, P = .011), and urinary tract infection (P = .002). PVR values were higher in patients with LUTS vs. those without (P = .011). Increased PVR correlated with male gender (P less than .001), EDSS score (P = .005), and disease course (P = .041). Higher PVR correlated with incontinence (P = .007), chronic urinary retention (P less than .001), incomplete emptying (P = .015), and diminished stream intensity (P = .040).
Study details: The findings are based on a study of 501 patients with clinically definite MS (68.9% females; mean age: 56.0 ± 12.3 years).
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Monti Bragadin M et al. Mult Scler Relat Disord. 2020 Jul 5. doi: 10.1016/j.msard.2020.102378.
Efficacy of disease-modifying therapies in treatment-naïve patients with MS
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), initiating high-efficacy disease-modifying therapies (heDMT) lowers the risk of Expanded Disability Status Scale (EDSS) score worsening and relapses compared to initiating medium-efficacy DMT (meDMT).
Major finding: The absolute probabilities of a 6-month confirmed EDSS score worsening at 2- and 4-year follow-ups were 11.5% and 16.7% for heDMT initiators and 18.3% and 30.1% for meDMT initiators, respectively (hazard ratio [HR], 0.53; P = .006). The heDMT initiators had a lower probability of a first relapse than meDMT initiators (HR, 0.50; 95% confidence interval, 0.37-0.67).
Study details: In this Danish population-based study, 194 patients with RRMS starting initial therapy with heDMT were matched to 194 patients starting meDMT.
Disclosures: There was no targeted funding. The presenting author reported receiving support for congress participation from Roche.
Citation: Buron MD et al. Neurology. 2020 Jul 7. doi: 10.1212/WNL.0000000000010135.
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), initiating high-efficacy disease-modifying therapies (heDMT) lowers the risk of Expanded Disability Status Scale (EDSS) score worsening and relapses compared to initiating medium-efficacy DMT (meDMT).
Major finding: The absolute probabilities of a 6-month confirmed EDSS score worsening at 2- and 4-year follow-ups were 11.5% and 16.7% for heDMT initiators and 18.3% and 30.1% for meDMT initiators, respectively (hazard ratio [HR], 0.53; P = .006). The heDMT initiators had a lower probability of a first relapse than meDMT initiators (HR, 0.50; 95% confidence interval, 0.37-0.67).
Study details: In this Danish population-based study, 194 patients with RRMS starting initial therapy with heDMT were matched to 194 patients starting meDMT.
Disclosures: There was no targeted funding. The presenting author reported receiving support for congress participation from Roche.
Citation: Buron MD et al. Neurology. 2020 Jul 7. doi: 10.1212/WNL.0000000000010135.
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), initiating high-efficacy disease-modifying therapies (heDMT) lowers the risk of Expanded Disability Status Scale (EDSS) score worsening and relapses compared to initiating medium-efficacy DMT (meDMT).
Major finding: The absolute probabilities of a 6-month confirmed EDSS score worsening at 2- and 4-year follow-ups were 11.5% and 16.7% for heDMT initiators and 18.3% and 30.1% for meDMT initiators, respectively (hazard ratio [HR], 0.53; P = .006). The heDMT initiators had a lower probability of a first relapse than meDMT initiators (HR, 0.50; 95% confidence interval, 0.37-0.67).
Study details: In this Danish population-based study, 194 patients with RRMS starting initial therapy with heDMT were matched to 194 patients starting meDMT.
Disclosures: There was no targeted funding. The presenting author reported receiving support for congress participation from Roche.
Citation: Buron MD et al. Neurology. 2020 Jul 7. doi: 10.1212/WNL.0000000000010135.
Personalized extended interval dosing does not reduce efficacy of natalizumab in MS
Key clinical point: Switching to personalized extended interval dosing of natalizumab did not result in recurrence of disease activity in stable patients with relapsing-remitting multiple sclerosis (RRMS).
Major finding: 84% of study patients extended the dosing interval from the standard 4 weeks to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI], 0-7.4%) during follow-up. No patient developed new/enlarging T2 lesions or relapses during the 1-year follow-up and 1-year extension phase.
Study details: The findings are based on a prospective, multicenter, single-arm trial of 61 patients with RRMS.
Disclosures: The study was funded by the Brain Foundation Netherlands. The presenting author had no disclosures. Some of the coauthors reported ties with pharmaceutical companies.
Citation: van Kempen ZLE et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000009995.
Key clinical point: Switching to personalized extended interval dosing of natalizumab did not result in recurrence of disease activity in stable patients with relapsing-remitting multiple sclerosis (RRMS).
Major finding: 84% of study patients extended the dosing interval from the standard 4 weeks to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI], 0-7.4%) during follow-up. No patient developed new/enlarging T2 lesions or relapses during the 1-year follow-up and 1-year extension phase.
Study details: The findings are based on a prospective, multicenter, single-arm trial of 61 patients with RRMS.
Disclosures: The study was funded by the Brain Foundation Netherlands. The presenting author had no disclosures. Some of the coauthors reported ties with pharmaceutical companies.
Citation: van Kempen ZLE et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000009995.
Key clinical point: Switching to personalized extended interval dosing of natalizumab did not result in recurrence of disease activity in stable patients with relapsing-remitting multiple sclerosis (RRMS).
Major finding: 84% of study patients extended the dosing interval from the standard 4 weeks to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI], 0-7.4%) during follow-up. No patient developed new/enlarging T2 lesions or relapses during the 1-year follow-up and 1-year extension phase.
Study details: The findings are based on a prospective, multicenter, single-arm trial of 61 patients with RRMS.
Disclosures: The study was funded by the Brain Foundation Netherlands. The presenting author had no disclosures. Some of the coauthors reported ties with pharmaceutical companies.
Citation: van Kempen ZLE et al. Neurology. 2020 Jul 20. doi: 10.1212/WNL.0000000000009995.
Secondary progressive MS: Sustained immunotherapy may improve disability outcomes
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
Key clinical point: Disease-modifying therapies (DMTs) are associated with improvements in disability outcomes in patients with active relapses during secondary progressive multiple sclerosis (SPMS).
Major finding: Patients who experienced superimposed relapses during SPMS and received DMTs had a greater proportion of time with a reduced Multiple Sclerosis Severity Score (MSSS) progression slope during SPMS (per 25% increase in proportion of time receiving treatment, β = −0.025; P less than .001 for low-efficacy; β = −0.022; P = .06 for medium-efficacy; and β = −0.034; P = .002 for high-efficacy therapies).
Study details: An observational cohort study of 1,621 patients with active SPMS from the international MSBase registry.
Disclosures: The study was supported by grants from the National Health and Medical Research Council. The MSBase Foundation receives funding from Bayer, bioCSL, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. The presenting author reported receiving travel compensation from Merck outside the submitted work.
Citation: Lizak N et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2453.
TNF inhibitors linked to inflammatory CNS events
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
, new research suggests
The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.
Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.
Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.
“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.
“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.
The findings were published in JAMA Neurology.
Poorly understood
TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.
Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.
In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis. The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.
In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
Novel finding?
Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.
Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”
In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).
A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).
“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.
Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.
Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
Adds to the literature
In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”
“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”
Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?
“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.
“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.
In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.
“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.
“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.
The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
A version of this article originally appeared on Medscape.com.
High-dose biotin treatment tied to increased risk of relapse in progressive MS
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger
Key clinical point: The follow-up of patients with progressive multiple sclerosis (PMS) starting high-dose biotin (HDB) should include careful assessment of clinical and radiological activity to monitor the potential pro-inflammatory effect of biotin.
Major finding: In the crossover analysis among patients who received HDB (n=42), the number of relapses was statistically and clinically significantly higher after vs. before biotin initiation (incident rate ratio, 7.4; P less than .0001). With the propensity score matching method, relapse risk was significantly higher in the biotin vs. control group (hazard ratio [HR], 4.3; P = .01). The inverse probability of treatment weighting method with 440 control participants showed consistent results with higher risk in the biotin group (HR, 5.1; P less than .0001).
Study details: This study evaluated the association between exposure to HDB and the risk of relapse among 482 patients with PMS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Branger
FDA approves ofatumumab (Kesimpta) for relapsing forms of MS
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.
“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.
Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.
Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.
Twin studies
Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.
The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.
As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.
The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.
Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).
The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.
Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.
The drug is expected to be available in the United States in September.
A version of this article originally appeared on Medscape.com.
Risk factors for severe COVID-19 in MS patients
Key clinical point: Age, disability, and obesity were independent risk factors for severe COVID-19 in patients with multiple sclerosis (MS).
Major finding: Higher age (odds ratio [OR] per 10 years, 1.9; 95% confidence interval [CI], 1.4-2.5), Expanded Disability Severity Status scores of ≥6 (OR, 6.3; 95% CI, 2.8-14.4), and obesity (OR, 3.0; 95% CI, 1.03-8.7) were independently associated with severe COVID-19 (severity score ≥3) Modification of disease-modifying therapies had no association with COVID-19 outcomes.
Study details: A multicenter, retrospective, observational cohort study analyzed data for 347 MS patients with confirmed or highly suspected COVID-19.
Disclosures: The study did not receive any specific funding. The authors reported relationships with multiple pharmaceutical companies and institutions.
Citation: Louapre C et al. JAMA Neurol. 2020 Jun 26. doi: 10.1001/jamaneurol.2020.2581.
Key clinical point: Age, disability, and obesity were independent risk factors for severe COVID-19 in patients with multiple sclerosis (MS).
Major finding: Higher age (odds ratio [OR] per 10 years, 1.9; 95% confidence interval [CI], 1.4-2.5), Expanded Disability Severity Status scores of ≥6 (OR, 6.3; 95% CI, 2.8-14.4), and obesity (OR, 3.0; 95% CI, 1.03-8.7) were independently associated with severe COVID-19 (severity score ≥3) Modification of disease-modifying therapies had no association with COVID-19 outcomes.
Study details: A multicenter, retrospective, observational cohort study analyzed data for 347 MS patients with confirmed or highly suspected COVID-19.
Disclosures: The study did not receive any specific funding. The authors reported relationships with multiple pharmaceutical companies and institutions.
Citation: Louapre C et al. JAMA Neurol. 2020 Jun 26. doi: 10.1001/jamaneurol.2020.2581.
Key clinical point: Age, disability, and obesity were independent risk factors for severe COVID-19 in patients with multiple sclerosis (MS).
Major finding: Higher age (odds ratio [OR] per 10 years, 1.9; 95% confidence interval [CI], 1.4-2.5), Expanded Disability Severity Status scores of ≥6 (OR, 6.3; 95% CI, 2.8-14.4), and obesity (OR, 3.0; 95% CI, 1.03-8.7) were independently associated with severe COVID-19 (severity score ≥3) Modification of disease-modifying therapies had no association with COVID-19 outcomes.
Study details: A multicenter, retrospective, observational cohort study analyzed data for 347 MS patients with confirmed or highly suspected COVID-19.
Disclosures: The study did not receive any specific funding. The authors reported relationships with multiple pharmaceutical companies and institutions.
Citation: Louapre C et al. JAMA Neurol. 2020 Jun 26. doi: 10.1001/jamaneurol.2020.2581.
MS: Rituximab effective in controlling disability and relapse rates
Key clinical point: Treatment with rituximab could effectively reduce disability levels and relapse rates in patients with multiple sclerosis (MS).
Major finding: The mean Expanded Disability Status Scale (EDSS) scores decreased by 0.29 (95% confidence interval [CI], 0.16-0.42) after rituximab treatment. Analysis of 3 studies showed a mean reduction in annualized relapse rates (–1.24; 95% CI, –1.04 to –1.44) after rituximab treatment. The overall proportion of adverse effects was 23% (95% CI, 20%-26%).
Study details: A systematic review and meta-analysis of 7 studies including 399 patients with MS treated with rituximab.
Disclosures: No information was available on funding and conflicts of interest.
Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Jun 10. doi:10.1016/j.autrev.2020.102585.
Key clinical point: Treatment with rituximab could effectively reduce disability levels and relapse rates in patients with multiple sclerosis (MS).
Major finding: The mean Expanded Disability Status Scale (EDSS) scores decreased by 0.29 (95% confidence interval [CI], 0.16-0.42) after rituximab treatment. Analysis of 3 studies showed a mean reduction in annualized relapse rates (–1.24; 95% CI, –1.04 to –1.44) after rituximab treatment. The overall proportion of adverse effects was 23% (95% CI, 20%-26%).
Study details: A systematic review and meta-analysis of 7 studies including 399 patients with MS treated with rituximab.
Disclosures: No information was available on funding and conflicts of interest.
Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Jun 10. doi:10.1016/j.autrev.2020.102585.
Key clinical point: Treatment with rituximab could effectively reduce disability levels and relapse rates in patients with multiple sclerosis (MS).
Major finding: The mean Expanded Disability Status Scale (EDSS) scores decreased by 0.29 (95% confidence interval [CI], 0.16-0.42) after rituximab treatment. Analysis of 3 studies showed a mean reduction in annualized relapse rates (–1.24; 95% CI, –1.04 to –1.44) after rituximab treatment. The overall proportion of adverse effects was 23% (95% CI, 20%-26%).
Study details: A systematic review and meta-analysis of 7 studies including 399 patients with MS treated with rituximab.
Disclosures: No information was available on funding and conflicts of interest.
Citation: Ghajarzadeh M et al. Autoimmun Rev. 2020 Jun 10. doi:10.1016/j.autrev.2020.102585.