Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.

Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.

Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.

Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.

Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6

Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.

Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.

Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.

Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.

Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6

Key clinical point: This real-world study confirms the safety, efficacy, and tolerability of remote electrical neuromodulation (REN) for long-term management of acute migraine, thus establishing REN as a valuable comprehensive treatment for this chronic disease.

Major finding: Overall, 74.1% and 26.0% of patients achieved consistent pain relief and pain freedom with REN, respectively, and 70.2% and 33.7% achieved functional disability relief and functional disability freedom, respectively. The incidence of device-related adverse events (dAE) was low, ie, 1.96%, which included 0.49% negligible, 1.22% moderate, and 0.24% mild AE. No severe AE were reported, and all patients continued treatment despite dAE.

Study details: This real-world evidence study included 409 patients with migraine treated for 12 consecutive months with REN, a self-administered device used at the onset of migraine headache or aura for acute treatment.

Disclosures: This study was funded by Theranica Bio-Electronics Ltd. M Weinstein and A Synowiec declared serving as consultants for Theranica. A Stark-Inbar and A Ironi declared being employees of and hold stock options in Theranica. A Mauskop had no conflicts of interest to disclose.

Source: Synowiec A et al. One-year consistent safety, utilization, and efficacy assessment of remote electrical neuromodulation (REN) for migraine treatment. Adv Ther. 2023 (Oct 19). doi: 10.1007/s12325-023-02697-6

Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.

Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.

Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.

Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.

Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8

Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.

Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.

Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.

Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.

Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8

Key clinical point: The use of ubrogepant in combination with anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) leads to meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization in patients with migraine.

Major finding: Following the first treated attack, 61.6% and 80.4% of patients achieved MPR and 34.7% and 55.5% of patients achieved RNF at 2 hours and 4 hours post-dose, respectively, in the ubrogepant plus anti-CGRP mAb arm. Moreover, 72.7% of patients reported being satisfied with ubrogepant when used in combination with anti-CGRP mAb, and 79.7% of patients achieved acute treatment optimization at 30 days.

Study details: Findings are from a prospective, observational study that included 245 patients with migraine who were treated with ubrogepant combined with anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention.

Disclosures: This study was funded by Allergan (prior to its acquisition by AbbVie). RB Lipton declared receiving research support, honoraria, and royalties from, and serving as a consultant and advisory board member for various sources, including AbbVie or Allergan.

Source: Lipton RB et al. Real-world use of ubrogepant as acute treatment for migraine with an anti-calcitonin gene-related peptide monoclonal antibody: Results from COURAGE. Neurol Ther. 2023 (Nov 1). doi: 10.1007/s40120-023-00556-8

Key clinical point: The introduction of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) has led to a reduction in the prescription of other oral preventive therapies for chronic migraine, likely due to the similar efficacy and better safety profile of CGRP mAb.

Major finding: Overall, the percentage of commonly prescribed preventive medications reduced significantly from 46.3% before the introduction of CGRP mAb to 43.1% post introduction (P = .001), including a large decrease in the prescription of verapamil, tricyclic antidepressants, topiramate, onabotulinumtoxinA, valproate, duloxetine, memantine, and propranolol (all P < .05).

Study details: This retrospective cohort study compared the percentage of patients with chronic migraine who were prescribed oral preventive medications or onabotulinumtoxinA during the CGRP mAb pre-approval period (2015-2017; n = 3144) and post-approval period (2019-2021; n = 4629).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Moskatel LS et al. The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis. Headache. 2023 (Oct 26). doi: 10.1111/head.14642

Key clinical point: The introduction of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) has led to a reduction in the prescription of other oral preventive therapies for chronic migraine, likely due to the similar efficacy and better safety profile of CGRP mAb.

Major finding: Overall, the percentage of commonly prescribed preventive medications reduced significantly from 46.3% before the introduction of CGRP mAb to 43.1% post introduction (P = .001), including a large decrease in the prescription of verapamil, tricyclic antidepressants, topiramate, onabotulinumtoxinA, valproate, duloxetine, memantine, and propranolol (all P < .05).

Study details: This retrospective cohort study compared the percentage of patients with chronic migraine who were prescribed oral preventive medications or onabotulinumtoxinA during the CGRP mAb pre-approval period (2015-2017; n = 3144) and post-approval period (2019-2021; n = 4629).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Moskatel LS et al. The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis. Headache. 2023 (Oct 26). doi: 10.1111/head.14642

Key clinical point: The introduction of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) has led to a reduction in the prescription of other oral preventive therapies for chronic migraine, likely due to the similar efficacy and better safety profile of CGRP mAb.

Major finding: Overall, the percentage of commonly prescribed preventive medications reduced significantly from 46.3% before the introduction of CGRP mAb to 43.1% post introduction (P = .001), including a large decrease in the prescription of verapamil, tricyclic antidepressants, topiramate, onabotulinumtoxinA, valproate, duloxetine, memantine, and propranolol (all P < .05).

Study details: This retrospective cohort study compared the percentage of patients with chronic migraine who were prescribed oral preventive medications or onabotulinumtoxinA during the CGRP mAb pre-approval period (2015-2017; n = 3144) and post-approval period (2019-2021; n = 4629).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Moskatel LS et al. The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis. Headache. 2023 (Oct 26). doi: 10.1111/head.14642

Key clinical point: Adolescents who are underweight or obese are at an increased risk for migraine, with the risk being more pronounced in case of women.

Major finding: Adolescent women who were underweight or obese had 12% (adjusted odds ratio [aOR] 1.12; 95% CI 1.05-1.19) and 38% (aOR 1.38; 95% CI 1.31-1.46) higher risks for migraine, respectively, than women with low-normal body mass index (BMI) values. Men who were underweight or obese had 11% (aOR 1.11; 95% CI 1.06-1.16) and 24% (aOR 1,24; 95% CI 1.19-1.30) higher risks for migraine, respectively, than men with low-normal BMI values.

Study details: The data come from a retrospective cross-sectional study including 2,094,862 adolescents (age 16-19 years), of whom 57,385 had migraine.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Zloof Y et al. Body mass index and migraine in adolescence: A nationwide study. Cephalalgia. 2023 (Oct 26). doi: 10.1177/03331024231209309

Key clinical point: Adolescents who are underweight or obese are at an increased risk for migraine, with the risk being more pronounced in case of women.

Major finding: Adolescent women who were underweight or obese had 12% (adjusted odds ratio [aOR] 1.12; 95% CI 1.05-1.19) and 38% (aOR 1.38; 95% CI 1.31-1.46) higher risks for migraine, respectively, than women with low-normal body mass index (BMI) values. Men who were underweight or obese had 11% (aOR 1.11; 95% CI 1.06-1.16) and 24% (aOR 1,24; 95% CI 1.19-1.30) higher risks for migraine, respectively, than men with low-normal BMI values.

Study details: The data come from a retrospective cross-sectional study including 2,094,862 adolescents (age 16-19 years), of whom 57,385 had migraine.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Zloof Y et al. Body mass index and migraine in adolescence: A nationwide study. Cephalalgia. 2023 (Oct 26). doi: 10.1177/03331024231209309

Key clinical point: Adolescents who are underweight or obese are at an increased risk for migraine, with the risk being more pronounced in case of women.

Major finding: Adolescent women who were underweight or obese had 12% (adjusted odds ratio [aOR] 1.12; 95% CI 1.05-1.19) and 38% (aOR 1.38; 95% CI 1.31-1.46) higher risks for migraine, respectively, than women with low-normal body mass index (BMI) values. Men who were underweight or obese had 11% (aOR 1.11; 95% CI 1.06-1.16) and 24% (aOR 1,24; 95% CI 1.19-1.30) higher risks for migraine, respectively, than men with low-normal BMI values.

Study details: The data come from a retrospective cross-sectional study including 2,094,862 adolescents (age 16-19 years), of whom 57,385 had migraine.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Zloof Y et al. Body mass index and migraine in adolescence: A nationwide study. Cephalalgia. 2023 (Oct 26). doi: 10.1177/03331024231209309

Key clinical point: Treatment with anti-calcitonin gene-related peptide (CGRP) antibodies for 3 months significantly improved depressive symptoms in patients with migraine, independent of the reduction in monthly migraine days (MMD).

Major finding: The proportion of patients with active depression reduced significantly after 3 months of treatment with erenumab and fremanezumab (both P < .001) but not in the group receiving no active treatment. Anti-CGRP medication vs no active medication led to additional reduction in the Hospital Anxiety and Depression Scale scores (β 1.65; P = .01), independent of the reduction in MMD.

Study details: This prospective study included patients with migraine who received erenumab (n = 110), fremanezumab (n = 117), or no active medication (n = 68).

Disclosures: This study did not disclose any funding sources. Three authors declared receiving consultancy support, industry grant, or independent support from various sources. The other authors declared no conflicts of interest.

Source: de Vries Lentsch S, van der Arend BWH, et al. Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine. Eur J Neurol. 2023 (Oct 17). doi: 10.1111/ene.16106

Key clinical point: Treatment with anti-calcitonin gene-related peptide (CGRP) antibodies for 3 months significantly improved depressive symptoms in patients with migraine, independent of the reduction in monthly migraine days (MMD).

Major finding: The proportion of patients with active depression reduced significantly after 3 months of treatment with erenumab and fremanezumab (both P < .001) but not in the group receiving no active treatment. Anti-CGRP medication vs no active medication led to additional reduction in the Hospital Anxiety and Depression Scale scores (β 1.65; P = .01), independent of the reduction in MMD.

Study details: This prospective study included patients with migraine who received erenumab (n = 110), fremanezumab (n = 117), or no active medication (n = 68).

Disclosures: This study did not disclose any funding sources. Three authors declared receiving consultancy support, industry grant, or independent support from various sources. The other authors declared no conflicts of interest.

Source: de Vries Lentsch S, van der Arend BWH, et al. Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine. Eur J Neurol. 2023 (Oct 17). doi: 10.1111/ene.16106

Key clinical point: Treatment with anti-calcitonin gene-related peptide (CGRP) antibodies for 3 months significantly improved depressive symptoms in patients with migraine, independent of the reduction in monthly migraine days (MMD).

Major finding: The proportion of patients with active depression reduced significantly after 3 months of treatment with erenumab and fremanezumab (both P < .001) but not in the group receiving no active treatment. Anti-CGRP medication vs no active medication led to additional reduction in the Hospital Anxiety and Depression Scale scores (β 1.65; P = .01), independent of the reduction in MMD.

Study details: This prospective study included patients with migraine who received erenumab (n = 110), fremanezumab (n = 117), or no active medication (n = 68).

Disclosures: This study did not disclose any funding sources. Three authors declared receiving consultancy support, industry grant, or independent support from various sources. The other authors declared no conflicts of interest.

Source: de Vries Lentsch S, van der Arend BWH, et al. Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine. Eur J Neurol. 2023 (Oct 17). doi: 10.1111/ene.16106

Key clinical point: This study provides class-III real-world evidence that anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) are efficacious and safe in patients with migraine age > 65 years but may take more time to show effect in these patients vs those age < 55 years.

Major finding: A similar proportion of patients age > 65 years vs < 55 years achieved a 50% response rate at 20-24 weeks of initiating anti-CGRP mAb (P = .811). Patients age > 65 years vs < 55 years showed lesser reduction in mean monthly headache days at 10-12 weeks (P = .001) and higher reduction in mean monthly migraine days at 20-24 weeks (P = .04). Both groups had similar incidence of treatment-emergent adverse events.

Study details: This multicenter observational case-control study included 114 patients age > 65 years and 114 sex-matched patients age < 55 years with episodic or chronic migraine who received anti-CGRP mAb.

Disclosures: This study did not receive any funding. Several authors declared receiving research support, speaker honoraria, or lecture honoraria from or serving on the advisory boards of various sources.

Source: Gonzalez-Martinez A et al. Effectiveness, tolerability and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: A multicenter real-world case-control study. Pain Med. 2023 (Oct 17). doi: 10.1093/pm/pnad141

Key clinical point: This study provides class-III real-world evidence that anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) are efficacious and safe in patients with migraine age > 65 years but may take more time to show effect in these patients vs those age < 55 years.

Major finding: A similar proportion of patients age > 65 years vs < 55 years achieved a 50% response rate at 20-24 weeks of initiating anti-CGRP mAb (P = .811). Patients age > 65 years vs < 55 years showed lesser reduction in mean monthly headache days at 10-12 weeks (P = .001) and higher reduction in mean monthly migraine days at 20-24 weeks (P = .04). Both groups had similar incidence of treatment-emergent adverse events.

Study details: This multicenter observational case-control study included 114 patients age > 65 years and 114 sex-matched patients age < 55 years with episodic or chronic migraine who received anti-CGRP mAb.

Disclosures: This study did not receive any funding. Several authors declared receiving research support, speaker honoraria, or lecture honoraria from or serving on the advisory boards of various sources.

Source: Gonzalez-Martinez A et al. Effectiveness, tolerability and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: A multicenter real-world case-control study. Pain Med. 2023 (Oct 17). doi: 10.1093/pm/pnad141

Key clinical point: This study provides class-III real-world evidence that anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) are efficacious and safe in patients with migraine age > 65 years but may take more time to show effect in these patients vs those age < 55 years.

Major finding: A similar proportion of patients age > 65 years vs < 55 years achieved a 50% response rate at 20-24 weeks of initiating anti-CGRP mAb (P = .811). Patients age > 65 years vs < 55 years showed lesser reduction in mean monthly headache days at 10-12 weeks (P = .001) and higher reduction in mean monthly migraine days at 20-24 weeks (P = .04). Both groups had similar incidence of treatment-emergent adverse events.

Study details: This multicenter observational case-control study included 114 patients age > 65 years and 114 sex-matched patients age < 55 years with episodic or chronic migraine who received anti-CGRP mAb.

Disclosures: This study did not receive any funding. Several authors declared receiving research support, speaker honoraria, or lecture honoraria from or serving on the advisory boards of various sources.

Source: Gonzalez-Martinez A et al. Effectiveness, tolerability and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: A multicenter real-world case-control study. Pain Med. 2023 (Oct 17). doi: 10.1093/pm/pnad141

Key clinical point: Three different ketogenic diets (KD)—very-low-calorie ketogenic diet (VLCKD), low-glycemic-index diet (LGID), and 2:1 KD—improved migraine frequency, migraine intensity, and fatigue in patients with chronic and high-frequency episodic migraine.

Major finding: At 3 months, all three KD led to a significant reduction in the fatigue severity scale (FSS) scores, along with reductions in the frequency and intensity of migraine attacks, Migraine Disability Assessment Test (MIDAS) scores, and Headache Impact Test 6 (HIT-6) scores (all P < .001). The mean reduction in FSS had positive correlation with the mean reduction in MIDAS (r = 0.361; P = .002) and HIT-6 (r = 0.344; P = .001) scores.

Study details: This retrospective single-center pilot study included 76 patients with chronic or high-frequency episodic migraine who followed three different KD                                 (VLCKD, LGID, or 2:1 KD) for ≥3 months.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Tereshko Y, Dal Bello S, et al. The effect of three different ketogenic diet protocols on migraine and fatigue in chronic and high-frequency episodic migraine: A pilot study. Nutrients. 2023;15(20):4334 (Oct 11). doi: 10.3390/nu15204334

Key clinical point: Three different ketogenic diets (KD)—very-low-calorie ketogenic diet (VLCKD), low-glycemic-index diet (LGID), and 2:1 KD—improved migraine frequency, migraine intensity, and fatigue in patients with chronic and high-frequency episodic migraine.

Major finding: At 3 months, all three KD led to a significant reduction in the fatigue severity scale (FSS) scores, along with reductions in the frequency and intensity of migraine attacks, Migraine Disability Assessment Test (MIDAS) scores, and Headache Impact Test 6 (HIT-6) scores (all P < .001). The mean reduction in FSS had positive correlation with the mean reduction in MIDAS (r = 0.361; P = .002) and HIT-6 (r = 0.344; P = .001) scores.

Study details: This retrospective single-center pilot study included 76 patients with chronic or high-frequency episodic migraine who followed three different KD                                 (VLCKD, LGID, or 2:1 KD) for ≥3 months.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Tereshko Y, Dal Bello S, et al. The effect of three different ketogenic diet protocols on migraine and fatigue in chronic and high-frequency episodic migraine: A pilot study. Nutrients. 2023;15(20):4334 (Oct 11). doi: 10.3390/nu15204334

Key clinical point: Three different ketogenic diets (KD)—very-low-calorie ketogenic diet (VLCKD), low-glycemic-index diet (LGID), and 2:1 KD—improved migraine frequency, migraine intensity, and fatigue in patients with chronic and high-frequency episodic migraine.

Major finding: At 3 months, all three KD led to a significant reduction in the fatigue severity scale (FSS) scores, along with reductions in the frequency and intensity of migraine attacks, Migraine Disability Assessment Test (MIDAS) scores, and Headache Impact Test 6 (HIT-6) scores (all P < .001). The mean reduction in FSS had positive correlation with the mean reduction in MIDAS (r = 0.361; P = .002) and HIT-6 (r = 0.344; P = .001) scores.

Study details: This retrospective single-center pilot study included 76 patients with chronic or high-frequency episodic migraine who followed three different KD                                 (VLCKD, LGID, or 2:1 KD) for ≥3 months.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Tereshko Y, Dal Bello S, et al. The effect of three different ketogenic diet protocols on migraine and fatigue in chronic and high-frequency episodic migraine: A pilot study. Nutrients. 2023;15(20):4334 (Oct 11). doi: 10.3390/nu15204334

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

SAN DIEGO – The use of abatacept (Orencia) in individuals at risk of developing rheumatoid arthritis is feasible, results from a proof-of-concept, phase 2b study showed.

The findings are encouraging because data from at-risk cohorts have reported rates of progression to RA in excess of 50% over 24 months, Andrew Cope, MBBS, PhD, head of the Center for Rheumatic Diseases at King’s College London, said during an abstract session at the annual meeting of the American College of Rheumatology. “If we’re going to do interception trials, we need to make sure that the risk-benefit is about right, and we also need to have enough events in the placebo arm against which to compare any impact of a drug,” he said.

For the randomized, placebo-controlled study known as the Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA) trial, Dr. Cope and colleagues at 28 sites in the United Kingdom and 3 in the Netherlands set out to evaluate the feasibility, efficacy, and acceptability of abatacept therapy in subjects at high risk of developing RA and to characterize the effects of T-cell costimulation modulation on the evaluation of immune and inflammatory responses associated with anti–citrullinated protein antibody (ACPA) prior to, during, and after therapy. They enrolled male and female individuals aged 18 and older with arthralgia, considered to be inflammatory in nature, and who were either ACPA and rheumatoid factor (RF) positive, or had high-titer ACPA. The researchers excluded individuals with clinically apparent arthritis, or a history of inflammatory arthritis as assessed by a rheumatologist, as well as those with a history or current use of conventional or targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs), or oral or parenteral use of corticosteroids. They also excluded people with comorbidities requiring treatment with immunosuppressive or immune-modulating therapy, those who had received a live vaccine in the prior 3 months, as well as those who were pregnant or breastfeeding.

Study participants were randomized 1:1 to receive 52 weekly subcutaneous injections of placebo or 125 mg abatacept and were followed for another 52 weeks. The primary endpoint was time to development of clinically apparent arthritis in at least three joints, or to fulfillment of the ACR/European Alliance of Associations for Rheumatology 2010 criteria for RA, whichever comes first, during 24 months of follow-up, with joint synovitis confirmed by ultrasound.

Dr. Cope reported results from 103 patients in the placebo arm and 110 patients in the abatacept arm. Their mean age was 49 years and 77% were female. At baseline, 73% of study participants had a power Doppler score of 0, which suggests minimal levels of active subclinical synovitis in a substantial proportion of this at-risk trial population. At 52 weeks, the researchers observed 30 events in the placebo arm (29%) and 7 in the abatacept arm (6%), while at 104 weeks, there were 38 events in the placebo arm (37%) and 27 in the abatacept arm (25%). This reflected a difference in mean arthritis-free survival time between arms of 99.2 days in favor of abatacept (P = .002).

Prespecified exploratory analysis showed that individuals with high levels of ACPA or who had an extended autoantibody profile at baseline were more likely to remain arthritis-free after abatacept therapy. “So, we’re seeing a hint here that there is an abatacept-sensitive population,” Dr. Cope said.

There were 7 serious adverse events in the abatacept group and 11 in the placebo group, including 2 deaths, 1 in each arm. None of the deaths were attributable to the study drug.

In other findings during the treatment phase, subjects in the abatacept arm, when compared to those in the placebo arm, had reduced levels of anxiety on the Hospital Anxiety Depression Scale; reduced fatigue, improved physical and emotional well-being, and improved functional well-being on the Functional Assessment of Chronic Illness Therapy-Fatigue measure; reduced sleep problems on the Symptoms in Persons at Risk of Rheumatoid Arthritis questionnaire; positive impact on work instability on the RA Work Instability Scale, and a positive impact on illness beliefs.

Based on the study findings, Dr. Cope concluded that clinical trials of RA interception are feasible, and that the rates of progression to RA are consistent with cohorts in other studies. “Abatacept reduced rates of progression to RA,” he said. “We also have data to suggest that the drug reduced subclinical inflammation as defined by ultrasound.”

One of the session moderators, Jon T. Giles, MD, MPH, associate professor of medicine at Columbia University, New York, asked Dr. Cope how he and his colleagues assessed the acceptability of abatacept. “Drug adherence is quite a good way to assess that, and we set the adherence level stringently at about 90%,” Dr. Cope said. “The nonadherence was about 26%. Getting people who don’t have disease to inject [the drug] weekly is not a trivial thing.”

Bristol-Myers Squibb funded the study. Dr. Cope disclosed that he has received grant support, consulting, and/or speakers bureau fees from GlaxoSmithKline, AbbVie, Janssen, Bristol-Myers Squibb, UCB, Galapagos, and Lilly. Many coauthors of the APIPPRA trial had financial relationships with multiple pharmaceutical companies, including Bristol-Myers Squibb. Dr. Giles disclosed that he is a consultant for AbbVie, Gilead, Lilly, Novartis, and Pfizer.

With the help of artificial intelligence (AI), arterial inflammation measured with coronary computed tomography angiography (CCTA) can predict fatal and nonfatal events in patients with nonobstructive coronary artery disease (CAD), according to a study that suggests this approach would change treatment about half the time.

In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.

This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.

Ted Bosworth/MDedge News

Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
 

CCTA-based inflammation is promising

The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.

So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.

In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).

The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.

When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.

The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.

“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
 

Predictive value greater in nonobstructive CAD

When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.

When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.

When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.

When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.

Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.

“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
 

Imaging has potential for expanded risk assessment

The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.

“A registry is not a randomized trial,” she said.

Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.

Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.

“This is an incredibly intriguing idea that deserves continuing research,” she said.

Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.

With the help of artificial intelligence (AI), arterial inflammation measured with coronary computed tomography angiography (CCTA) can predict fatal and nonfatal events in patients with nonobstructive coronary artery disease (CAD), according to a study that suggests this approach would change treatment about half the time.

In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.

This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.

Ted Bosworth/MDedge News

Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
 

CCTA-based inflammation is promising

The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.

So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.

In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).

The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.

When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.

The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.

“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
 

Predictive value greater in nonobstructive CAD

When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.

When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.

When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.

When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.

Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.

“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
 

Imaging has potential for expanded risk assessment

The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.

“A registry is not a randomized trial,” she said.

Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.

Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.

“This is an incredibly intriguing idea that deserves continuing research,” she said.

Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.

With the help of artificial intelligence (AI), arterial inflammation measured with coronary computed tomography angiography (CCTA) can predict fatal and nonfatal events in patients with nonobstructive coronary artery disease (CAD), according to a study that suggests this approach would change treatment about half the time.

In patients with nonobstructive CAD, CCTA measurement of inflammation on the basis of the Fat Attenuation Index (FAI) “predicts fatal and nonfatal cardiac events independently from clinical risk scores and routine CCTA interpretation,” reported Charalambos Antoniades, MD, PhD, professor of cardiology, Radcliffe Department of Medicine, Oxford, England.

This analysis was based on data from ORFAN, an ongoing study that expects to eventually collect data from 250,000 CCTA. There were multiple goals. The first was to evaluate whether there is a need and a role of CCTA to risk stratify patients without obstructive CAD. A second objective was to evaluate if the FAI inflammation score can quantify residual risk in these patients.

Ted Bosworth/MDedge News

Based on the answers to these questions, the investigators then proceeded to determine if an AI risk model that combines data from the FAI score and risk factors is widely generalizable and, in addition, whether it reclassifies patients in a way meaningful to management.
 

CCTA-based inflammation is promising

The answers to all these questions were yes, according to data presented by Dr. Antoniades in a late-breaker at the American Heart Association scientific sessions.

So far, ORPHAN, which has multiple participating sites in the United Kingdom, Europe, United States, South America, Asia, and Australia, have data on more than 100,000 CCTAs. Approximately 40,000 have been processed. Of these, 82% have had nonobstructive CAD and the remaining obstructive disease.

In long-term follow-up, the numbers of major adverse cardiovascular events (MACE) and cardiac deaths were compared in these two groups. In absolute terms, the nonobstructive CAD group had about twice as many MACE (2,587 vs. 1,450) and cardiac deaths (1,118 vs. 636).

The rate of these events was much lower in the nonobstructive group , which had four times more patients than the obstructive group, but Dr. Antoniades said these data demonstrate substantial rates of events in the nonobstructive group as well as an unmet need to identify and treat risk associated with nonobstructive CAD.

When determining if coronary inflammation as measured with CCTA could be a means identifying risk independent of other factors, the FAI scores were evaluated by quartile in a nested cohort of 3,666 consecutive patients. FAI, which has been validated, is calculated with spatial changes in CCTA-measured perivascular fat composition after standardization for anatomy and other variables.

The discrimination for risk with FAI was impressive. When evaluated across all patients (obstructive or nonobstructive CAD), those in the highest FAI quartile had a hazard ratio (HR) for MACE that was more than six times higher (HR 6.76; P < .001) and a risk of cardiac mortality that was more than 20 times higher (HR 20.20; P < .001) than that of those in the first quartile.

“The prediction was independent of all other risk factors,” Dr. Antoniades reported.
 

Predictive value greater in nonobstructive CAD

When evaluated in nonobstructive disease, the predictive value of FAI was even greater. In obstructive CAD patients, the increased risk of MACE for the fourth relative to the first quartile was increased threefold (HR 3.15; P < .001), but it was increased almost fivefold among those with nonobstructive CAD (HR 4.77; P < .001). The increases for cardiac mortality were fivefold (HR 5.15; P < .001) and more than 10-fold (HR 10.49; P < .001) in these groups, respectively.

When a risk model based on AI that incorporated FAI plus other cardiovascular risk factors was applied retrospectively to the ORPHAN data, the predicted and actual event graph lines were nearly superimposable over a follow-up to 10 years at risk levels ranging from low to very high.

When this inflammation-based AI model was evaluated against standard risk prediction in patients with nonobstructive CAD, 30% of patients were reclassified to a higher risk category and 10% to a lower risk category.

When the AI-risk calculations were provided to clinicians at four hospitals over a recent 1-year period, it resulted “in changes of management in approximately half of patients,” Dr. Antoniades said.

Overall, Dr. Antoniades said these data provide evidence that coronary inflammation is an important driver of residual risk in patients who have nonobstructive CAD on CCTA, and he believes that the AI-enhanced interpretation of the FAI-based inflammatory burden has the potential to become an important management tool.

“AI-risk assessment may transform risk stratification and management of patients undergoing routine CCTA,” Dr. Antoniades said.
 

Imaging has potential for expanded risk assessment

The AHA-invited discussant, Viviany R. Taqueti, MD, director of the cardiac stress laboratory at Brigham and Women’s Hospital, Boston, agreed with the promise of evaluating inflammatory infiltrate in the coronary arteries as well as looking at fat in other tissues, such as skeletal muscle, to better risk stratify patients, but she cautioned about the limitations of conclusions based on observational data.

“A registry is not a randomized trial,” she said.

Characterizing AI as a “black box” in terms of understanding methodology, she also recommended further studies to validate the relative contribution of AI to inflammation alone in risk stratification.

Still, she believes that the “explosive growth” in imaging has created new opportunities for more precisely evaluating cardiovascular risk. She said these might be particularly helpful in the context of the “changing landscape” in CAD driven by less smoking, more obesity, and increased statin use. Overall, she endorsed the basic questions Dr. Antoniades is exploring.

“This is an incredibly intriguing idea that deserves continuing research,” she said.

Dr. Antoniades reported financial relationships with Amarin, AstraZeneca, Caristo Diagnostics, Covance, Mitsubishi Tanabe, MedImmune, Novo Nordisk, Sanofi, and Silence Therapeutics. Dr. Taqueti reported no potential conflicts of interest.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.

SAN DIEGO – In pregnant women with systemic lupus erythematosus (SLE), those with ill-timed pregnancies had poorer pregnancy outcomes, including preeclampsia and preterm birth.

Women with autoimmune conditions are at an increased risk for pregnancy complications, including pregnancy loss, preterm delivery, and increased need for cesarean delivery, said Catherine Sims, MD, a rheumatologist at Duke Health in Durham, N.C., who is focused on reproductive rheumatology. “The natural question, both clinically and from a research perspective, is: ‘What can we do in order to mitigate or minimize these complications?’ ” she said during a presentation at the annual meeting of the American College of Rheumatology.

Lucy Hicks/Medscape Medical News

While research suggests that patients who plan their pregnancies during times of well-controlled disease have the “best chances of improved pregnancy outcomes,” Dr. Sims and colleagues wanted to quantify how planning for pregnancy affected reproductive outcomes.

Dr. Sims recruited pregnant women with SLE and assessed if the women were medically optimized for pregnancy, if the pregnancy was intended, or both. Intended pregnancy was assessed by using a validated self-reported survey called the London Measure of Unplanned Pregnancy. Pregnant women were considered “medically optimized” for pregnancy if they were not on teratogenic medication, had continued pregnancy-compatible SLE medications, and had a urine protein-creatinine ratio of less than 1 gram in the 6 months prior to or during the first trimester. Intended pregnancies that were medically optimized were classified as “well timed.”

Of the 115 women enrolled in the study, about half had well-timed pregnancies, 20% were neither intended nor medically optimized, 17% were not intended but medically optimized, and 13% were intended but not medically optimized.

Women with ill-timed pregnancy – either not medically optimized and/or unintended – were generally younger and more likely to be single, on Medicare or Medicaid, and on income of less than $50,000 per year.

Ill-timed pregnancies had higher rates of mycophenolate exposure and higher physician-reported SLE disease activity. While patient-reported SLE activity was higher in patients who were not personally ready for pregnancy, in patients who had an intended pregnancy, there was no difference in self-reported SLE activity between those that were medically optimized and those not medically optimized.

“About a third of our patients are actually underestimating their true disease activity level when they are preparing for pregnancy,” Dr. Sims said. For example, while persistent proteinuria in a patient would drive up physician assessment of disease activity, the patient may not be experiencing any symptoms and is unaware of her condition.

In terms of pregnancy outcomes, women with unintended pregnancies had a 2.5 times higher incidence of preeclampsia, compared with those with intended pregnancies. Patients with unplanned pregnancies were also significantly more likely to experience stillbirth.

Women who were not medically optimized for pregnancy were three times as likely to experience preterm birth and preeclampsia compared with those with optimized pregnancies.

These outcomes drive home the importance of optimizing patients for pregnancy, Dr. Sims said, and effectively communicating this importance to patients, especially when they might not be perceiving their disease activity.

The study’s findings show providers “what we thought we knew, which is that there are some patients that are not as aware of their risk,” commented Lisa R. Sammaritano, MD, Hospital for Special Surgery, New York, who moderated the session where the research was presented. “It brings home the importance of counselling our patients about contraception [as well as] the importance of planning.”

Dr. Sims added that it is “crucial” to make this information easily accessible and digestible to patients. One important resource she mentioned is the HOP-STEP program, which stands for Healthy Outcomes in Pregnancy with SLE Through Education of Providers. The program, directed by researchers at Duke University, is designed to improve pregnancy planning in people with lupus. Direct-to-patient resources are key, she said, as patients can often be nervous to ask about pregnancy planning during appointments.

“They won’t want to bring a pregnancy with me in clinic because they’re afraid I’m just going to say, ‘don’t do it,’ ” Dr. Sims said. “But we are making decisions with the patient. Our patients are not asking for permission, but telling us what they want, and we need to meet them where they are at.”

A version of this article appeared on Medscape.com.