Key clinical point: Atezolizumab plus bevacizumab (AtezoBev) is an effective therapeutic option for unresectable hepatocellular carcinoma (uHCC) in routine clinical practice and is safe even in patients with Child-Pugh (CP)-B grade liver function.

Major finding: After a 9-month median follow-up, median overall survival was 14.9 months (95% CI 13.6-16.3 months) and median progression-free survival was 6.8 months (95% CI 5.2-8.5 months). Tolerability was similar across CP classes, with comparable bevacizumab-related (CP-A, 48%; CP-B, 46%) and atezolizumab-related (CP-A, 53%; CP-B, 40%) adverse event rates of any grade.

Study details: This was a multicenter retrospective study that included 202 adult patients with uHCC and CP-A (76%) or CP-B (24%) cirrhosis who received AtezoBev as the first-line systemic treatment.

Disclosures: The study was funded by the National Institute of Health Research Imperial Biomedical Research Centre, among others. Some authors declared serving as consultants or advisors for or receiving advisory board honoraria, lecture/speaker fees, research grants, or travel/accommodation expenses from various sources.

Source: D'Alessio A et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. Hepatology. 2022 (Mar 21). Doi: 10.1002/hep.32468

Key clinical point: Atezolizumab plus bevacizumab (AtezoBev) is an effective therapeutic option for unresectable hepatocellular carcinoma (uHCC) in routine clinical practice and is safe even in patients with Child-Pugh (CP)-B grade liver function.

Major finding: After a 9-month median follow-up, median overall survival was 14.9 months (95% CI 13.6-16.3 months) and median progression-free survival was 6.8 months (95% CI 5.2-8.5 months). Tolerability was similar across CP classes, with comparable bevacizumab-related (CP-A, 48%; CP-B, 46%) and atezolizumab-related (CP-A, 53%; CP-B, 40%) adverse event rates of any grade.

Study details: This was a multicenter retrospective study that included 202 adult patients with uHCC and CP-A (76%) or CP-B (24%) cirrhosis who received AtezoBev as the first-line systemic treatment.

Disclosures: The study was funded by the National Institute of Health Research Imperial Biomedical Research Centre, among others. Some authors declared serving as consultants or advisors for or receiving advisory board honoraria, lecture/speaker fees, research grants, or travel/accommodation expenses from various sources.

Source: D'Alessio A et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. Hepatology. 2022 (Mar 21). Doi: 10.1002/hep.32468

Key clinical point: Atezolizumab plus bevacizumab (AtezoBev) is an effective therapeutic option for unresectable hepatocellular carcinoma (uHCC) in routine clinical practice and is safe even in patients with Child-Pugh (CP)-B grade liver function.

Major finding: After a 9-month median follow-up, median overall survival was 14.9 months (95% CI 13.6-16.3 months) and median progression-free survival was 6.8 months (95% CI 5.2-8.5 months). Tolerability was similar across CP classes, with comparable bevacizumab-related (CP-A, 48%; CP-B, 46%) and atezolizumab-related (CP-A, 53%; CP-B, 40%) adverse event rates of any grade.

Study details: This was a multicenter retrospective study that included 202 adult patients with uHCC and CP-A (76%) or CP-B (24%) cirrhosis who received AtezoBev as the first-line systemic treatment.

Disclosures: The study was funded by the National Institute of Health Research Imperial Biomedical Research Centre, among others. Some authors declared serving as consultants or advisors for or receiving advisory board honoraria, lecture/speaker fees, research grants, or travel/accommodation expenses from various sources.

Source: D'Alessio A et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. Hepatology. 2022 (Mar 21). Doi: 10.1002/hep.32468

Key clinical point: Postoperative adjuvant stereotactic body radiotherapy (SBRT) on suboptimal resection margin safely and effectively improves disease-free survival (DFS) and prevents local recurrence in microvascular invasion (MVI)-positive hepatocellular carcinoma (HCC).

Major finding: SBRT vs. surgery alone led to significantly higher 1-year (92.1% vs. 76.3%) and 5-year (56.1% vs. 26.3%) DFS rates (P = .005) and similar local recurrence (P = .236) rates. No grade ≥3 adverse events were noted.

Study details: This randomized controlled trial included 76 adult patients with MVI-positive HCC who underwent marginal resection and were randomly assigned to receive postoperative adjuvant SBRT or surgery alone.

Disclosures: The study was funded by the Clinical Science and Technology Innovation Project of Shenkang Hospital Development Center, Shanghai Jiading District Fund, and Shanghai Municipal Health Commission Program, China. No conflicts of interest were reported.

Source: Shi C et al. Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with microvascular invasion: A randomised controlled trial. Eur J Cancer. 2022;166:176-184 (Mar 16). Doi: 10.1016/j.ejca.2022.02.012

Key clinical point: Postoperative adjuvant stereotactic body radiotherapy (SBRT) on suboptimal resection margin safely and effectively improves disease-free survival (DFS) and prevents local recurrence in microvascular invasion (MVI)-positive hepatocellular carcinoma (HCC).

Major finding: SBRT vs. surgery alone led to significantly higher 1-year (92.1% vs. 76.3%) and 5-year (56.1% vs. 26.3%) DFS rates (P = .005) and similar local recurrence (P = .236) rates. No grade ≥3 adverse events were noted.

Study details: This randomized controlled trial included 76 adult patients with MVI-positive HCC who underwent marginal resection and were randomly assigned to receive postoperative adjuvant SBRT or surgery alone.

Disclosures: The study was funded by the Clinical Science and Technology Innovation Project of Shenkang Hospital Development Center, Shanghai Jiading District Fund, and Shanghai Municipal Health Commission Program, China. No conflicts of interest were reported.

Source: Shi C et al. Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with microvascular invasion: A randomised controlled trial. Eur J Cancer. 2022;166:176-184 (Mar 16). Doi: 10.1016/j.ejca.2022.02.012

Key clinical point: Postoperative adjuvant stereotactic body radiotherapy (SBRT) on suboptimal resection margin safely and effectively improves disease-free survival (DFS) and prevents local recurrence in microvascular invasion (MVI)-positive hepatocellular carcinoma (HCC).

Major finding: SBRT vs. surgery alone led to significantly higher 1-year (92.1% vs. 76.3%) and 5-year (56.1% vs. 26.3%) DFS rates (P = .005) and similar local recurrence (P = .236) rates. No grade ≥3 adverse events were noted.

Study details: This randomized controlled trial included 76 adult patients with MVI-positive HCC who underwent marginal resection and were randomly assigned to receive postoperative adjuvant SBRT or surgery alone.

Disclosures: The study was funded by the Clinical Science and Technology Innovation Project of Shenkang Hospital Development Center, Shanghai Jiading District Fund, and Shanghai Municipal Health Commission Program, China. No conflicts of interest were reported.

Source: Shi C et al. Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with microvascular invasion: A randomised controlled trial. Eur J Cancer. 2022;166:176-184 (Mar 16). Doi: 10.1016/j.ejca.2022.02.012

Key clinical point: Compared with other liver disease etiologies, nonalcoholic fatty liver disease (NAFLD) was associated with lower hepatocellular carcinoma (HCC) surveillance receipt and early-stage detection, thus calling for interventions for increased surveillance implementation and improved prognosis of patients with NAFLD-related HCC.

Major finding: NAFLD vs. hepatitis C virus etiology was associated with a lower likelihood of consistent or inconsistent HCC surveillance receipt (adjusted odds ratio [aOR] 0.37; 95% CI 0.32-0.44) and detection of early-stage HCC (aOR 0.49; 95% CI 0.40-0.60) and worse overall survival (adjusted hazard ratio 1.20; 95% CI 1.09-1.32).

Study details: This was a population-based cohort study of US Medicare beneficiaries including 5098 patients aged ≥68 years with HCC, which was attributable to NAFLD in most patients (35.6%).

Disclosures: The study was funded by the American College of Gastroenterology, US Department of Defense, and US National Institute of Health. Some authors reported being consultants, advisory board members, or shareholders of and receiving research grants from various organizations.

Source: Karim MA et al. Clinical characteristics and outcomes of nonalcoholic fatty liver disease–associated hepatocellular carcinoma in the United States. Clin Gastroenterol Hepatol. 2022 (Mar 17). Doi: 10.1016/j.cgh.2022.03.010

Key clinical point: Compared with other liver disease etiologies, nonalcoholic fatty liver disease (NAFLD) was associated with lower hepatocellular carcinoma (HCC) surveillance receipt and early-stage detection, thus calling for interventions for increased surveillance implementation and improved prognosis of patients with NAFLD-related HCC.

Major finding: NAFLD vs. hepatitis C virus etiology was associated with a lower likelihood of consistent or inconsistent HCC surveillance receipt (adjusted odds ratio [aOR] 0.37; 95% CI 0.32-0.44) and detection of early-stage HCC (aOR 0.49; 95% CI 0.40-0.60) and worse overall survival (adjusted hazard ratio 1.20; 95% CI 1.09-1.32).

Study details: This was a population-based cohort study of US Medicare beneficiaries including 5098 patients aged ≥68 years with HCC, which was attributable to NAFLD in most patients (35.6%).

Disclosures: The study was funded by the American College of Gastroenterology, US Department of Defense, and US National Institute of Health. Some authors reported being consultants, advisory board members, or shareholders of and receiving research grants from various organizations.

Source: Karim MA et al. Clinical characteristics and outcomes of nonalcoholic fatty liver disease–associated hepatocellular carcinoma in the United States. Clin Gastroenterol Hepatol. 2022 (Mar 17). Doi: 10.1016/j.cgh.2022.03.010

Key clinical point: Compared with other liver disease etiologies, nonalcoholic fatty liver disease (NAFLD) was associated with lower hepatocellular carcinoma (HCC) surveillance receipt and early-stage detection, thus calling for interventions for increased surveillance implementation and improved prognosis of patients with NAFLD-related HCC.

Major finding: NAFLD vs. hepatitis C virus etiology was associated with a lower likelihood of consistent or inconsistent HCC surveillance receipt (adjusted odds ratio [aOR] 0.37; 95% CI 0.32-0.44) and detection of early-stage HCC (aOR 0.49; 95% CI 0.40-0.60) and worse overall survival (adjusted hazard ratio 1.20; 95% CI 1.09-1.32).

Study details: This was a population-based cohort study of US Medicare beneficiaries including 5098 patients aged ≥68 years with HCC, which was attributable to NAFLD in most patients (35.6%).

Disclosures: The study was funded by the American College of Gastroenterology, US Department of Defense, and US National Institute of Health. Some authors reported being consultants, advisory board members, or shareholders of and receiving research grants from various organizations.

Source: Karim MA et al. Clinical characteristics and outcomes of nonalcoholic fatty liver disease–associated hepatocellular carcinoma in the United States. Clin Gastroenterol Hepatol. 2022 (Mar 17). Doi: 10.1016/j.cgh.2022.03.010

Key clinical point: In hepatitis B e-antigen (HBeAg)-positive, non-cirrhotic, adult patients with chronic hepatitis B (CHB) and baseline hepatitis B virus (HBV) DNA levels of ≥5.00 log₁₀ IU/mL, pretreatment baseline serum HBV DNA levels were inversely associated with the on-treatment risk for hepatocellular carcinoma (HCC).

Major finding: Relative to that at HBV DNA levels of ≥8.00 log₁₀ IU/mL, HCC risk increased incrementally with a decrease in baseline HBV DNA levels, with the adjusted hazard ratios for 7.00-7.99, 6.00-6.99, and 5.00-5.99 log₁₀ IU/mL of HBV DNA being 2.48 (P = .03), 3.69 (P = .002), and 6.10 (P < .001), respectively.

Study details: The findings are from a multicenter cohort study involving 2073 HBeAg-positive, non-cirrhotic, treatment-naive, adult patients with CHB who had baseline HBV DNA levels of ≥5.00 log₁₀ IU/mL and had initiated treatment with entecavir or tenofovir disoproxil fumarate.

Disclosures: The study was sponsored by the Ministry of Health & Welfare, Republic of Korea. Y-S Lim declared being an advisory board member of and receiving research funds from Gilead Sciences.

Source: Choi W-M et al. Increasing on-treatment hepatocellular carcinoma risk with decreasing baseline viral load in HBeAg-positive chronic hepatitis B. J Clin Invest. 2022 (Mar 31). Doi: 10.1172/JCI154833

Key clinical point: In hepatitis B e-antigen (HBeAg)-positive, non-cirrhotic, adult patients with chronic hepatitis B (CHB) and baseline hepatitis B virus (HBV) DNA levels of ≥5.00 log₁₀ IU/mL, pretreatment baseline serum HBV DNA levels were inversely associated with the on-treatment risk for hepatocellular carcinoma (HCC).

Major finding: Relative to that at HBV DNA levels of ≥8.00 log₁₀ IU/mL, HCC risk increased incrementally with a decrease in baseline HBV DNA levels, with the adjusted hazard ratios for 7.00-7.99, 6.00-6.99, and 5.00-5.99 log₁₀ IU/mL of HBV DNA being 2.48 (P = .03), 3.69 (P = .002), and 6.10 (P < .001), respectively.

Study details: The findings are from a multicenter cohort study involving 2073 HBeAg-positive, non-cirrhotic, treatment-naive, adult patients with CHB who had baseline HBV DNA levels of ≥5.00 log₁₀ IU/mL and had initiated treatment with entecavir or tenofovir disoproxil fumarate.

Disclosures: The study was sponsored by the Ministry of Health & Welfare, Republic of Korea. Y-S Lim declared being an advisory board member of and receiving research funds from Gilead Sciences.

Source: Choi W-M et al. Increasing on-treatment hepatocellular carcinoma risk with decreasing baseline viral load in HBeAg-positive chronic hepatitis B. J Clin Invest. 2022 (Mar 31). Doi: 10.1172/JCI154833

Key clinical point: In hepatitis B e-antigen (HBeAg)-positive, non-cirrhotic, adult patients with chronic hepatitis B (CHB) and baseline hepatitis B virus (HBV) DNA levels of ≥5.00 log₁₀ IU/mL, pretreatment baseline serum HBV DNA levels were inversely associated with the on-treatment risk for hepatocellular carcinoma (HCC).

Major finding: Relative to that at HBV DNA levels of ≥8.00 log₁₀ IU/mL, HCC risk increased incrementally with a decrease in baseline HBV DNA levels, with the adjusted hazard ratios for 7.00-7.99, 6.00-6.99, and 5.00-5.99 log₁₀ IU/mL of HBV DNA being 2.48 (P = .03), 3.69 (P = .002), and 6.10 (P < .001), respectively.

Study details: The findings are from a multicenter cohort study involving 2073 HBeAg-positive, non-cirrhotic, treatment-naive, adult patients with CHB who had baseline HBV DNA levels of ≥5.00 log₁₀ IU/mL and had initiated treatment with entecavir or tenofovir disoproxil fumarate.

Disclosures: The study was sponsored by the Ministry of Health & Welfare, Republic of Korea. Y-S Lim declared being an advisory board member of and receiving research funds from Gilead Sciences.

Source: Choi W-M et al. Increasing on-treatment hepatocellular carcinoma risk with decreasing baseline viral load in HBeAg-positive chronic hepatitis B. J Clin Invest. 2022 (Mar 31). Doi: 10.1172/JCI154833

Key clinical point: Long-term aspirin use may reduce the risk for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection.

Major finding: After adjusting for confounding factors, aspirin use was associated with a decreased likelihood of HCC in the entire population (adjusted hazard ratio [aHR] 0.84; P = .002) and in the matched cohort (aHR 0.87; P = .01).

Study details: The data come from a cohort study including 161,673 patients aged ≥40 years with chronic HBV infection and no history of HCC, of which 9837 patients were aspirin users (for ≥3 years). A 1:4 propensity score matching yielded 9837 matched pairs of users and nonusers.

Disclosures: The study was sponsored by the Korea Health Industry Development Institute through “Social and Environmental Risk Research” funded by the Ministry of Health & Welfare. The authors declared no conflicts of interest.

Source: Yun B et al. Clinical indication of aspirin associated with reduced risk of liver cancer in chronic hepatitis B: A nationwide cohort study. Am J Gastroenterol. 2022 (Mar 14). Doi: 10.14309/ajg.0000000000001725

Key clinical point: Long-term aspirin use may reduce the risk for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection.

Major finding: After adjusting for confounding factors, aspirin use was associated with a decreased likelihood of HCC in the entire population (adjusted hazard ratio [aHR] 0.84; P = .002) and in the matched cohort (aHR 0.87; P = .01).

Study details: The data come from a cohort study including 161,673 patients aged ≥40 years with chronic HBV infection and no history of HCC, of which 9837 patients were aspirin users (for ≥3 years). A 1:4 propensity score matching yielded 9837 matched pairs of users and nonusers.

Disclosures: The study was sponsored by the Korea Health Industry Development Institute through “Social and Environmental Risk Research” funded by the Ministry of Health & Welfare. The authors declared no conflicts of interest.

Source: Yun B et al. Clinical indication of aspirin associated with reduced risk of liver cancer in chronic hepatitis B: A nationwide cohort study. Am J Gastroenterol. 2022 (Mar 14). Doi: 10.14309/ajg.0000000000001725

Key clinical point: Long-term aspirin use may reduce the risk for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection.

Major finding: After adjusting for confounding factors, aspirin use was associated with a decreased likelihood of HCC in the entire population (adjusted hazard ratio [aHR] 0.84; P = .002) and in the matched cohort (aHR 0.87; P = .01).

Study details: The data come from a cohort study including 161,673 patients aged ≥40 years with chronic HBV infection and no history of HCC, of which 9837 patients were aspirin users (for ≥3 years). A 1:4 propensity score matching yielded 9837 matched pairs of users and nonusers.

Disclosures: The study was sponsored by the Korea Health Industry Development Institute through “Social and Environmental Risk Research” funded by the Ministry of Health & Welfare. The authors declared no conflicts of interest.

Source: Yun B et al. Clinical indication of aspirin associated with reduced risk of liver cancer in chronic hepatitis B: A nationwide cohort study. Am J Gastroenterol. 2022 (Mar 14). Doi: 10.14309/ajg.0000000000001725

Key clinical point: Hormone therapy with Duavee®, containing conjugated estrogens (0.45 mg) and bazedoxifene (20 mg), yielded a favorable study retention and treatment satisfaction in menopausal women with multiple sclerosis (MS).

Major finding: Patients receiving Duavee® vs. placebo had a fewer missed doses (median, interquartile range [IQR] 0 [0-0] vs. 1 [0-9]), a greater Global Satisfaction on the Treatment Satisfaction Questionnaire for Medication (median, IQR 65.9 [52.8-100] vs. 62.5 [11.1-93.0]), and lesser side effects (20% vs. 13%), with none of the patients reporting a clinical relapse.

Study details: Findings are from a double-blind phase 1b/2a trial involving 21 peri/postmenopausal women with MS who were randomly assigned to parallel groups of Duavee® or equivalent placebo for 8 weeks.

Disclosures: This study was funded the National Multiple Sclerosis Society pilot grant and CTSI grant. Some authors declared receiving research support, personal compensation, speaker fees, or nonfinancial support from various sources, including Wyeth/Pfizer, the manufacturer of Duavee®. Several authors are provisional patent holders for the use of bazedoxifene in remyelination therapy.

Source: Bove R et al. A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial. Mult Scler Relat Disord. 2022;67:103747 (Mar 19). Doi:  10.1016/j.msard.2022.103747

Key clinical point: Hormone therapy with Duavee®, containing conjugated estrogens (0.45 mg) and bazedoxifene (20 mg), yielded a favorable study retention and treatment satisfaction in menopausal women with multiple sclerosis (MS).

Major finding: Patients receiving Duavee® vs. placebo had a fewer missed doses (median, interquartile range [IQR] 0 [0-0] vs. 1 [0-9]), a greater Global Satisfaction on the Treatment Satisfaction Questionnaire for Medication (median, IQR 65.9 [52.8-100] vs. 62.5 [11.1-93.0]), and lesser side effects (20% vs. 13%), with none of the patients reporting a clinical relapse.

Study details: Findings are from a double-blind phase 1b/2a trial involving 21 peri/postmenopausal women with MS who were randomly assigned to parallel groups of Duavee® or equivalent placebo for 8 weeks.

Disclosures: This study was funded the National Multiple Sclerosis Society pilot grant and CTSI grant. Some authors declared receiving research support, personal compensation, speaker fees, or nonfinancial support from various sources, including Wyeth/Pfizer, the manufacturer of Duavee®. Several authors are provisional patent holders for the use of bazedoxifene in remyelination therapy.

Source: Bove R et al. A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial. Mult Scler Relat Disord. 2022;67:103747 (Mar 19). Doi:  10.1016/j.msard.2022.103747

Key clinical point: Hormone therapy with Duavee®, containing conjugated estrogens (0.45 mg) and bazedoxifene (20 mg), yielded a favorable study retention and treatment satisfaction in menopausal women with multiple sclerosis (MS).

Major finding: Patients receiving Duavee® vs. placebo had a fewer missed doses (median, interquartile range [IQR] 0 [0-0] vs. 1 [0-9]), a greater Global Satisfaction on the Treatment Satisfaction Questionnaire for Medication (median, IQR 65.9 [52.8-100] vs. 62.5 [11.1-93.0]), and lesser side effects (20% vs. 13%), with none of the patients reporting a clinical relapse.

Study details: Findings are from a double-blind phase 1b/2a trial involving 21 peri/postmenopausal women with MS who were randomly assigned to parallel groups of Duavee® or equivalent placebo for 8 weeks.

Disclosures: This study was funded the National Multiple Sclerosis Society pilot grant and CTSI grant. Some authors declared receiving research support, personal compensation, speaker fees, or nonfinancial support from various sources, including Wyeth/Pfizer, the manufacturer of Duavee®. Several authors are provisional patent holders for the use of bazedoxifene in remyelination therapy.

Source: Bove R et al. A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial. Mult Scler Relat Disord. 2022;67:103747 (Mar 19). Doi:  10.1016/j.msard.2022.103747

Key clinical point: Pregnancy may have a protective effect on the risk of developing multiple sclerosis (MS) in addition to a hypothesized reverse causality.

Major finding: Women with MS vs. women without any autoimmune disease were less likely to record the 18 pregnancy-related gynecological International Classification of Diseases 10th Revision codes, with strongest negative correlation observed for the supervision of normal pregnancy (adjusted P = 9.12 × 10⁻²⁷) and high-risk pregnancy (adjusted P = 2.49 × 10⁻¹²).

Study details: Findings are from a retrospective case-control study including women with newly diagnosed MS (n = 5720) and three control cohorts of women with newly diagnosed Crohn’s Disease (n = 6280), psoriasis (n = 26,729), and women without any of the three autoimmune diseases (n = 40,555).

Disclosures: The study was funded by European Union’s Horizon 2020 Research and Innovation Program, Hertie Foundation, and the Hans and Klementia Langmatz Stiftung, among others. B Hemmer declared serving on scientific advisory boards and receiving speaker honoraria and research funding from various sources. The other authors declared no conflicts of interest.

Citation: Gasperi C et al. Association of pregnancies with risk of multiple sclerosis. Mult Scler. 2022 (Mar 18). Doi: 10.1177/13524585221080542

Key clinical point: Pregnancy may have a protective effect on the risk of developing multiple sclerosis (MS) in addition to a hypothesized reverse causality.

Major finding: Women with MS vs. women without any autoimmune disease were less likely to record the 18 pregnancy-related gynecological International Classification of Diseases 10th Revision codes, with strongest negative correlation observed for the supervision of normal pregnancy (adjusted P = 9.12 × 10⁻²⁷) and high-risk pregnancy (adjusted P = 2.49 × 10⁻¹²).

Study details: Findings are from a retrospective case-control study including women with newly diagnosed MS (n = 5720) and three control cohorts of women with newly diagnosed Crohn’s Disease (n = 6280), psoriasis (n = 26,729), and women without any of the three autoimmune diseases (n = 40,555).

Disclosures: The study was funded by European Union’s Horizon 2020 Research and Innovation Program, Hertie Foundation, and the Hans and Klementia Langmatz Stiftung, among others. B Hemmer declared serving on scientific advisory boards and receiving speaker honoraria and research funding from various sources. The other authors declared no conflicts of interest.

Citation: Gasperi C et al. Association of pregnancies with risk of multiple sclerosis. Mult Scler. 2022 (Mar 18). Doi: 10.1177/13524585221080542

Key clinical point: Pregnancy may have a protective effect on the risk of developing multiple sclerosis (MS) in addition to a hypothesized reverse causality.

Major finding: Women with MS vs. women without any autoimmune disease were less likely to record the 18 pregnancy-related gynecological International Classification of Diseases 10th Revision codes, with strongest negative correlation observed for the supervision of normal pregnancy (adjusted P = 9.12 × 10⁻²⁷) and high-risk pregnancy (adjusted P = 2.49 × 10⁻¹²).

Study details: Findings are from a retrospective case-control study including women with newly diagnosed MS (n = 5720) and three control cohorts of women with newly diagnosed Crohn’s Disease (n = 6280), psoriasis (n = 26,729), and women without any of the three autoimmune diseases (n = 40,555).

Disclosures: The study was funded by European Union’s Horizon 2020 Research and Innovation Program, Hertie Foundation, and the Hans and Klementia Langmatz Stiftung, among others. B Hemmer declared serving on scientific advisory boards and receiving speaker honoraria and research funding from various sources. The other authors declared no conflicts of interest.

Citation: Gasperi C et al. Association of pregnancies with risk of multiple sclerosis. Mult Scler. 2022 (Mar 18). Doi: 10.1177/13524585221080542

Key clinical point: Genetic liability to multiple sclerosis (MS) was associated with an increased risk for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), all-cause stroke (AS), and any ischemic stroke (AIS), but not atrial fibrillation (AF) or other stroke subtypes.

Major finding: Genetic liability to MS was associated with an increased risk for CAD (odds ratio [OR] 1.02; P = .03), MI (OR 1.03; P = .01), HF (OR 1.02; P = .02), AS (OR 1.02; P = .02), and AIS (OR 1.02; P = .04), but not with AF or other stroke subtypes.

Study details: This was a two-sample Mendelian randomization analysis of genetic summary data for 47,429 MS (68,374 healthy controls [HC]), 60,801 CAD (123,504 HC), and 43,676 MI (128,199 HC), 60,620 AF (970,216 HC), and 47,309 HF (930,014 HC) cases from large-scale genome-wide association studies.

Disclosures: The study was supported by grants from Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang, China, the Major Project of Science and Technology Innovation 2025 in Ningbo, and others. The authors declared no conflicts of interest.

Source: Yang F et al. Multiple sclerosis and the risk of cardiovascular diseases: A Mendelian randomization study. Front Immunol. 2022;13:861885 (Mar 15). Doi: 10.3389/fimmu.2022.861885

Key clinical point: Genetic liability to multiple sclerosis (MS) was associated with an increased risk for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), all-cause stroke (AS), and any ischemic stroke (AIS), but not atrial fibrillation (AF) or other stroke subtypes.

Major finding: Genetic liability to MS was associated with an increased risk for CAD (odds ratio [OR] 1.02; P = .03), MI (OR 1.03; P = .01), HF (OR 1.02; P = .02), AS (OR 1.02; P = .02), and AIS (OR 1.02; P = .04), but not with AF or other stroke subtypes.

Study details: This was a two-sample Mendelian randomization analysis of genetic summary data for 47,429 MS (68,374 healthy controls [HC]), 60,801 CAD (123,504 HC), and 43,676 MI (128,199 HC), 60,620 AF (970,216 HC), and 47,309 HF (930,014 HC) cases from large-scale genome-wide association studies.

Disclosures: The study was supported by grants from Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang, China, the Major Project of Science and Technology Innovation 2025 in Ningbo, and others. The authors declared no conflicts of interest.

Source: Yang F et al. Multiple sclerosis and the risk of cardiovascular diseases: A Mendelian randomization study. Front Immunol. 2022;13:861885 (Mar 15). Doi: 10.3389/fimmu.2022.861885

Key clinical point: Genetic liability to multiple sclerosis (MS) was associated with an increased risk for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), all-cause stroke (AS), and any ischemic stroke (AIS), but not atrial fibrillation (AF) or other stroke subtypes.

Major finding: Genetic liability to MS was associated with an increased risk for CAD (odds ratio [OR] 1.02; P = .03), MI (OR 1.03; P = .01), HF (OR 1.02; P = .02), AS (OR 1.02; P = .02), and AIS (OR 1.02; P = .04), but not with AF or other stroke subtypes.

Study details: This was a two-sample Mendelian randomization analysis of genetic summary data for 47,429 MS (68,374 healthy controls [HC]), 60,801 CAD (123,504 HC), and 43,676 MI (128,199 HC), 60,620 AF (970,216 HC), and 47,309 HF (930,014 HC) cases from large-scale genome-wide association studies.

Disclosures: The study was supported by grants from Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang, China, the Major Project of Science and Technology Innovation 2025 in Ningbo, and others. The authors declared no conflicts of interest.

Source: Yang F et al. Multiple sclerosis and the risk of cardiovascular diseases: A Mendelian randomization study. Front Immunol. 2022;13:861885 (Mar 15). Doi: 10.3389/fimmu.2022.861885

Key clinical point: Maintaining natalizumab until conception and restarting within 1 month after delivery (treatment approach [TA]) reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery (conservative approach [CA]) in women with multiple sclerosis (MS), with no major development abnormalities noted in infants.

Major finding: Relapses occurred in 29.4% vs. 70.2% (P = .001) of patients in TA vs. CA after a mean follow-up of 6.1 years, with the CA being the only predictor of relapses (hazard ratio 4.1; P = .003). No developmental abnormalities were observed in infants.

Study details: Findings are from a cohort study of 72 pregnancies in 70 women with MS who were treated with natalizumab and were followed-up for at least 2 years.

Disclosures: No financial support was received. The authors declared receiving research support, travel, consulting, and speaker fees or personal compensation or serving on advisory boards for various sources.

Citation: Portaccio E et al. Natalizumab treatment and pregnancy in multiple sclerosis: A reappraisal of maternal and infant outcomes after 6 years. Mult Scler. 2022 (Mar 16). Doi: 10.1177/13524585221079598

Key clinical point: Maintaining natalizumab until conception and restarting within 1 month after delivery (treatment approach [TA]) reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery (conservative approach [CA]) in women with multiple sclerosis (MS), with no major development abnormalities noted in infants.

Major finding: Relapses occurred in 29.4% vs. 70.2% (P = .001) of patients in TA vs. CA after a mean follow-up of 6.1 years, with the CA being the only predictor of relapses (hazard ratio 4.1; P = .003). No developmental abnormalities were observed in infants.

Study details: Findings are from a cohort study of 72 pregnancies in 70 women with MS who were treated with natalizumab and were followed-up for at least 2 years.

Disclosures: No financial support was received. The authors declared receiving research support, travel, consulting, and speaker fees or personal compensation or serving on advisory boards for various sources.

Citation: Portaccio E et al. Natalizumab treatment and pregnancy in multiple sclerosis: A reappraisal of maternal and infant outcomes after 6 years. Mult Scler. 2022 (Mar 16). Doi: 10.1177/13524585221079598

Key clinical point: Maintaining natalizumab until conception and restarting within 1 month after delivery (treatment approach [TA]) reduced the risk for disease activity more than natalizumab cessation before conception or restarting 1 month after delivery (conservative approach [CA]) in women with multiple sclerosis (MS), with no major development abnormalities noted in infants.

Major finding: Relapses occurred in 29.4% vs. 70.2% (P = .001) of patients in TA vs. CA after a mean follow-up of 6.1 years, with the CA being the only predictor of relapses (hazard ratio 4.1; P = .003). No developmental abnormalities were observed in infants.

Study details: Findings are from a cohort study of 72 pregnancies in 70 women with MS who were treated with natalizumab and were followed-up for at least 2 years.

Disclosures: No financial support was received. The authors declared receiving research support, travel, consulting, and speaker fees or personal compensation or serving on advisory boards for various sources.

Citation: Portaccio E et al. Natalizumab treatment and pregnancy in multiple sclerosis: A reappraisal of maternal and infant outcomes after 6 years. Mult Scler. 2022 (Mar 16). Doi: 10.1177/13524585221079598

Key clinical point: Progression independent of relapse activity (PIRA) is a major contributor of confirmed disability accrual (CDA) in early relapsing-onset multiple sclerosis (MS), with age being a major determinant of the way CDA occurs.

Major finding: PIRA accounted for 27.6% of disability worsening events, whereas relapse-associated worsening (RAW) accounted for 17.8% of events, with RAW being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients.

Study details: Findings are from a retrospective cohort analysis of 5169 patients with clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥5 years.

Disclosures: No source of funding was declared. Some authors declared serving on advisory boards or receiving grants, travel compensation, speaker honoraria, or lecture and consulting fees from various sources.

Source: Portaccio E et al. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study. Brain. 2022 (Mar 24). Doi: 10.1093/brain/awac111

Key clinical point: Progression independent of relapse activity (PIRA) is a major contributor of confirmed disability accrual (CDA) in early relapsing-onset multiple sclerosis (MS), with age being a major determinant of the way CDA occurs.

Major finding: PIRA accounted for 27.6% of disability worsening events, whereas relapse-associated worsening (RAW) accounted for 17.8% of events, with RAW being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients.

Study details: Findings are from a retrospective cohort analysis of 5169 patients with clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥5 years.

Disclosures: No source of funding was declared. Some authors declared serving on advisory boards or receiving grants, travel compensation, speaker honoraria, or lecture and consulting fees from various sources.

Source: Portaccio E et al. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study. Brain. 2022 (Mar 24). Doi: 10.1093/brain/awac111

Key clinical point: Progression independent of relapse activity (PIRA) is a major contributor of confirmed disability accrual (CDA) in early relapsing-onset multiple sclerosis (MS), with age being a major determinant of the way CDA occurs.

Major finding: PIRA accounted for 27.6% of disability worsening events, whereas relapse-associated worsening (RAW) accounted for 17.8% of events, with RAW being more frequent in younger (hazard ratio [HR] 0.87) and PIRA in older (HR 1.19; both P < .001) patients.

Study details: Findings are from a retrospective cohort analysis of 5169 patients with clinically isolated syndrome or early relapsing-remitting MS who were assessed within 1 year of onset and followed-up for ≥5 years.

Disclosures: No source of funding was declared. Some authors declared serving on advisory boards or receiving grants, travel compensation, speaker honoraria, or lecture and consulting fees from various sources.

Source: Portaccio E et al. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study. Brain. 2022 (Mar 24). Doi: 10.1093/brain/awac111