Multiple Sclerosis

Key clinical point: In patients with multiple sclerosis (MS) without good recovery after the initial relapse, initiating a disease-modifying therapy (DMT) immediately increases the likelihood of a benign disease course.

Major finding: Patients with good recovery and immediate DMT initiation and those with poor recovery and delayed DMT initiation had about 65% and 20% chance, respectively, of remaining at a minimal disability level (Expanded Disability Status Scale score of less than 2.5) by age 45 years.

Study details: An analysis of data from the phase 3 CHAMPS trial in clinically isolated syndrome (n=383) and 10-year follow-up EXTENSION trial.

Disclosures: This study was funded by an unrestricted grant to Dr. Kantarci from Biogen. Dr. Kantarci and Dr. Atkinson received salary support as part of the grant from Biogen. Dr. Castrillo-Viguera was employed by Biogen.

Citation: Kantarci OH et al. Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17. doi: 10.1212/NXI.0000000000000653. 

Key clinical point: In patients with multiple sclerosis (MS) without good recovery after the initial relapse, initiating a disease-modifying therapy (DMT) immediately increases the likelihood of a benign disease course.

Major finding: Patients with good recovery and immediate DMT initiation and those with poor recovery and delayed DMT initiation had about 65% and 20% chance, respectively, of remaining at a minimal disability level (Expanded Disability Status Scale score of less than 2.5) by age 45 years.

Study details: An analysis of data from the phase 3 CHAMPS trial in clinically isolated syndrome (n=383) and 10-year follow-up EXTENSION trial.

Disclosures: This study was funded by an unrestricted grant to Dr. Kantarci from Biogen. Dr. Kantarci and Dr. Atkinson received salary support as part of the grant from Biogen. Dr. Castrillo-Viguera was employed by Biogen.

Citation: Kantarci OH et al. Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17. doi: 10.1212/NXI.0000000000000653. 

Key clinical point: In patients with multiple sclerosis (MS) without good recovery after the initial relapse, initiating a disease-modifying therapy (DMT) immediately increases the likelihood of a benign disease course.

Major finding: Patients with good recovery and immediate DMT initiation and those with poor recovery and delayed DMT initiation had about 65% and 20% chance, respectively, of remaining at a minimal disability level (Expanded Disability Status Scale score of less than 2.5) by age 45 years.

Study details: An analysis of data from the phase 3 CHAMPS trial in clinically isolated syndrome (n=383) and 10-year follow-up EXTENSION trial.

Disclosures: This study was funded by an unrestricted grant to Dr. Kantarci from Biogen. Dr. Kantarci and Dr. Atkinson received salary support as part of the grant from Biogen. Dr. Castrillo-Viguera was employed by Biogen.

Citation: Kantarci OH et al. Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17. doi: 10.1212/NXI.0000000000000653. 

Key clinical point: Phase 3 EVOLVE-MS-2 study demonstrates that diroximel fumarate (DRF) has an improved gastrointestinal (GI) tolerability profile compared with dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (MS).

Major finding: Patients treated with DRF self-reported 46% fewer days with an Individual Gastrointestinal Symptom and Impact Scale (IGISIS) symptom intensity score of ≥2 vs those treated with DMF (rate ratio, 0.54; 95% confidence interval, 0.39-0.75). The rates of GI adverse events (AEs) were lower with DRF than DMF (34.8% vs. 49.0%). DRF-treated patients had a lower discontinuation rate because of GI AEs (0.8% vs. 4.8%) and overall AEs (1.6% vs. 5.6%).

Study details: EVOLVE-MS-2 was a 5-week randomized trial that directly compared the GI tolerability of DRF 462 mg (n = 253) with that of DMF 240 mg (n = 249); primary endpoint was the number of days with an IGISIS intensity score of 2 or greater relative to exposure.

Disclosures: This study was funded by Alkermes Inc. and Biogen. The authors reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Naismith RT et al. CNS Drugs. 2020 Jan 17. doi: 10.1007/s40263-020-00700-0. 

Key clinical point: Phase 3 EVOLVE-MS-2 study demonstrates that diroximel fumarate (DRF) has an improved gastrointestinal (GI) tolerability profile compared with dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (MS).

Major finding: Patients treated with DRF self-reported 46% fewer days with an Individual Gastrointestinal Symptom and Impact Scale (IGISIS) symptom intensity score of ≥2 vs those treated with DMF (rate ratio, 0.54; 95% confidence interval, 0.39-0.75). The rates of GI adverse events (AEs) were lower with DRF than DMF (34.8% vs. 49.0%). DRF-treated patients had a lower discontinuation rate because of GI AEs (0.8% vs. 4.8%) and overall AEs (1.6% vs. 5.6%).

Study details: EVOLVE-MS-2 was a 5-week randomized trial that directly compared the GI tolerability of DRF 462 mg (n = 253) with that of DMF 240 mg (n = 249); primary endpoint was the number of days with an IGISIS intensity score of 2 or greater relative to exposure.

Disclosures: This study was funded by Alkermes Inc. and Biogen. The authors reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Naismith RT et al. CNS Drugs. 2020 Jan 17. doi: 10.1007/s40263-020-00700-0. 

Key clinical point: Phase 3 EVOLVE-MS-2 study demonstrates that diroximel fumarate (DRF) has an improved gastrointestinal (GI) tolerability profile compared with dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (MS).

Major finding: Patients treated with DRF self-reported 46% fewer days with an Individual Gastrointestinal Symptom and Impact Scale (IGISIS) symptom intensity score of ≥2 vs those treated with DMF (rate ratio, 0.54; 95% confidence interval, 0.39-0.75). The rates of GI adverse events (AEs) were lower with DRF than DMF (34.8% vs. 49.0%). DRF-treated patients had a lower discontinuation rate because of GI AEs (0.8% vs. 4.8%) and overall AEs (1.6% vs. 5.6%).

Study details: EVOLVE-MS-2 was a 5-week randomized trial that directly compared the GI tolerability of DRF 462 mg (n = 253) with that of DMF 240 mg (n = 249); primary endpoint was the number of days with an IGISIS intensity score of 2 or greater relative to exposure.

Disclosures: This study was funded by Alkermes Inc. and Biogen. The authors reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Naismith RT et al. CNS Drugs. 2020 Jan 17. doi: 10.1007/s40263-020-00700-0. 

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

Key clinical point: Ozanimod has a superior benefit-risk profile compared with fingolimod for the treatment of relapsing multiple sclerosis (RMS).

Major finding: Compared with fingolimod, ozanimod was associated with lower rates of conduction abnormalities (risk difference, −3.5%) and first-degree atrioventricular block (risk difference, −3.0%), lower risk of extended first-dose cardiac monitoring, and lower risk of adverse events over 1-2 years of follow-up. Efficacy outcomes were comparable.

Study details: Using a matching-adjusted indirect comparison, the first-dose cardiac monitoring outcomes and 1- and 2-year safety and efficacy outcomes were compared for ozanimod and fingolimod in patients with RMS.

Disclosures: The study received research support from Celgene, a wholly-owned subsidiary of Bristol-Myers Squibb. Five authors are employees of Bristol-Myers Squibb. Four authors are employees of Analysis Group, Inc., who have received consulting fees from Bristol-Myers Squibb.

Citation: Swallow E et al. J Comp Eff Res. 2020 Jan 17. doi: 10.2217/cer-2019-0169.

Key clinical point: Ozanimod has a superior benefit-risk profile compared with fingolimod for the treatment of relapsing multiple sclerosis (RMS).

Major finding: Compared with fingolimod, ozanimod was associated with lower rates of conduction abnormalities (risk difference, −3.5%) and first-degree atrioventricular block (risk difference, −3.0%), lower risk of extended first-dose cardiac monitoring, and lower risk of adverse events over 1-2 years of follow-up. Efficacy outcomes were comparable.

Study details: Using a matching-adjusted indirect comparison, the first-dose cardiac monitoring outcomes and 1- and 2-year safety and efficacy outcomes were compared for ozanimod and fingolimod in patients with RMS.

Disclosures: The study received research support from Celgene, a wholly-owned subsidiary of Bristol-Myers Squibb. Five authors are employees of Bristol-Myers Squibb. Four authors are employees of Analysis Group, Inc., who have received consulting fees from Bristol-Myers Squibb.

Citation: Swallow E et al. J Comp Eff Res. 2020 Jan 17. doi: 10.2217/cer-2019-0169.

Key clinical point: Ozanimod has a superior benefit-risk profile compared with fingolimod for the treatment of relapsing multiple sclerosis (RMS).

Major finding: Compared with fingolimod, ozanimod was associated with lower rates of conduction abnormalities (risk difference, −3.5%) and first-degree atrioventricular block (risk difference, −3.0%), lower risk of extended first-dose cardiac monitoring, and lower risk of adverse events over 1-2 years of follow-up. Efficacy outcomes were comparable.

Study details: Using a matching-adjusted indirect comparison, the first-dose cardiac monitoring outcomes and 1- and 2-year safety and efficacy outcomes were compared for ozanimod and fingolimod in patients with RMS.

Disclosures: The study received research support from Celgene, a wholly-owned subsidiary of Bristol-Myers Squibb. Five authors are employees of Bristol-Myers Squibb. Four authors are employees of Analysis Group, Inc., who have received consulting fees from Bristol-Myers Squibb.

Citation: Swallow E et al. J Comp Eff Res. 2020 Jan 17. doi: 10.2217/cer-2019-0169.

Key clinical point: Polypharmacy is common in patients with multiple sclerosis (MS) and is negatively associated with health outcomes.

Major finding: The rates of polypharmacy among patients with MS ranged from 14.9% to 59% across the studies that were reviewed. Polypharmacy was significantly associated with increased hospitalization rates, cognitive deficits, fatigue, higher relapse rates, and a lower quality of life, particularly among elderly patients.

Study details: The data come from a qualitative systematic review of 7 studies.  

Disclosures: Niklas Frahm has received travel funds for research meetings from Novartis. Michael Hecker received speaking fees and travel funds from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva. Uwe Klaus Zettl received research support and lecture fees or travel funds from Almirall, Alexion, Bayer HealthCare, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva.

Citation: Frahm N et al. Expert Opin Drug Saf. 2020 Jan 27. doi: 10.1080/14740338.2020.1720646.

Key clinical point: Polypharmacy is common in patients with multiple sclerosis (MS) and is negatively associated with health outcomes.

Major finding: The rates of polypharmacy among patients with MS ranged from 14.9% to 59% across the studies that were reviewed. Polypharmacy was significantly associated with increased hospitalization rates, cognitive deficits, fatigue, higher relapse rates, and a lower quality of life, particularly among elderly patients.

Study details: The data come from a qualitative systematic review of 7 studies.  

Disclosures: Niklas Frahm has received travel funds for research meetings from Novartis. Michael Hecker received speaking fees and travel funds from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva. Uwe Klaus Zettl received research support and lecture fees or travel funds from Almirall, Alexion, Bayer HealthCare, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva.

Citation: Frahm N et al. Expert Opin Drug Saf. 2020 Jan 27. doi: 10.1080/14740338.2020.1720646.

Key clinical point: Polypharmacy is common in patients with multiple sclerosis (MS) and is negatively associated with health outcomes.

Major finding: The rates of polypharmacy among patients with MS ranged from 14.9% to 59% across the studies that were reviewed. Polypharmacy was significantly associated with increased hospitalization rates, cognitive deficits, fatigue, higher relapse rates, and a lower quality of life, particularly among elderly patients.

Study details: The data come from a qualitative systematic review of 7 studies.  

Disclosures: Niklas Frahm has received travel funds for research meetings from Novartis. Michael Hecker received speaking fees and travel funds from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva. Uwe Klaus Zettl received research support and lecture fees or travel funds from Almirall, Alexion, Bayer HealthCare, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva.

Citation: Frahm N et al. Expert Opin Drug Saf. 2020 Jan 27. doi: 10.1080/14740338.2020.1720646.

Key clinical point: Air pollution may be a potential etiological factor in the development of multiple sclerosis (MS).

Major finding: The age-standardized prevalence of MS was found to be 97.4 per 100,000 persons in the polluted city and 47.2 per 100,000 persons in the rural and clean city.

Study details: A cross-sectional, population-based, epidemiologic study compared the prevalence of MS among 2 cities in Turkey: Eregli city, which has an iron-and-steel factory with known air pollution, and Devrek city, which is a rural and clean city.

Disclosures: The authors declared no conflicts of interest.

Citation: Börü UT et al. Acta Neurol Scand. 2020 Jan 18. doi: 10.1111/ane.13223.

Key clinical point: Air pollution may be a potential etiological factor in the development of multiple sclerosis (MS).

Major finding: The age-standardized prevalence of MS was found to be 97.4 per 100,000 persons in the polluted city and 47.2 per 100,000 persons in the rural and clean city.

Study details: A cross-sectional, population-based, epidemiologic study compared the prevalence of MS among 2 cities in Turkey: Eregli city, which has an iron-and-steel factory with known air pollution, and Devrek city, which is a rural and clean city.

Disclosures: The authors declared no conflicts of interest.

Citation: Börü UT et al. Acta Neurol Scand. 2020 Jan 18. doi: 10.1111/ane.13223.

Key clinical point: Air pollution may be a potential etiological factor in the development of multiple sclerosis (MS).

Major finding: The age-standardized prevalence of MS was found to be 97.4 per 100,000 persons in the polluted city and 47.2 per 100,000 persons in the rural and clean city.

Study details: A cross-sectional, population-based, epidemiologic study compared the prevalence of MS among 2 cities in Turkey: Eregli city, which has an iron-and-steel factory with known air pollution, and Devrek city, which is a rural and clean city.

Disclosures: The authors declared no conflicts of interest.

Citation: Börü UT et al. Acta Neurol Scand. 2020 Jan 18. doi: 10.1111/ane.13223.

Key clinical point: Patients with relapse-remitting multiple sclerosis (RRMS) have a high prevalence of alexithymia.

Major finding: Alexithymia was observed in about 29.55% of patients and borderline alexithymia was observed in 31.15% of patients; alexithymia positively correlated with anxiety and depression in patients with RRMS (P less than .01). 

Study details: The data come from a cross-sectional study that included 106 consecutively assessed adult patients with RRMS (74 female and 32 male patients). 

Disclosures: The authors declared no conflicts of interest.

Citation: Stojanov J et al. J Postgrad Med. 2020 Jan 13. doi: 10.4103/jpgm.JPGM_499_19.

Key clinical point: Patients with relapse-remitting multiple sclerosis (RRMS) have a high prevalence of alexithymia.

Major finding: Alexithymia was observed in about 29.55% of patients and borderline alexithymia was observed in 31.15% of patients; alexithymia positively correlated with anxiety and depression in patients with RRMS (P less than .01). 

Study details: The data come from a cross-sectional study that included 106 consecutively assessed adult patients with RRMS (74 female and 32 male patients). 

Disclosures: The authors declared no conflicts of interest.

Citation: Stojanov J et al. J Postgrad Med. 2020 Jan 13. doi: 10.4103/jpgm.JPGM_499_19.

Key clinical point: Patients with relapse-remitting multiple sclerosis (RRMS) have a high prevalence of alexithymia.

Major finding: Alexithymia was observed in about 29.55% of patients and borderline alexithymia was observed in 31.15% of patients; alexithymia positively correlated with anxiety and depression in patients with RRMS (P less than .01). 

Study details: The data come from a cross-sectional study that included 106 consecutively assessed adult patients with RRMS (74 female and 32 male patients). 

Disclosures: The authors declared no conflicts of interest.

Citation: Stojanov J et al. J Postgrad Med. 2020 Jan 13. doi: 10.4103/jpgm.JPGM_499_19.

Key clinical point: Patients with multiple sclerosis (MS) have a high prevalence of lower urinary tract symptoms (LUTS).

Major finding: The prevalence of LUTS among patients with MS was 87.7%. The likelihood of urinary problems was higher in patients with a high Expanded Disability Status Scale score (adjusted odds ratio, 0.677; 95% CI, 0.507-0.903; P = .008).

Study details: The data come from a cross-sectional study that included 602 patients with MS. 

Disclosures: The authors declared no conflicts of interest.

Citation: Nazari F et al. BMC Neurol. 2020 Jan 17. doi: 10.1186/s12883-019-1582-1. 

Key clinical point: Patients with multiple sclerosis (MS) have a high prevalence of lower urinary tract symptoms (LUTS).

Major finding: The prevalence of LUTS among patients with MS was 87.7%. The likelihood of urinary problems was higher in patients with a high Expanded Disability Status Scale score (adjusted odds ratio, 0.677; 95% CI, 0.507-0.903; P = .008).

Study details: The data come from a cross-sectional study that included 602 patients with MS. 

Disclosures: The authors declared no conflicts of interest.

Citation: Nazari F et al. BMC Neurol. 2020 Jan 17. doi: 10.1186/s12883-019-1582-1. 

Key clinical point: Patients with multiple sclerosis (MS) have a high prevalence of lower urinary tract symptoms (LUTS).

Major finding: The prevalence of LUTS among patients with MS was 87.7%. The likelihood of urinary problems was higher in patients with a high Expanded Disability Status Scale score (adjusted odds ratio, 0.677; 95% CI, 0.507-0.903; P = .008).

Study details: The data come from a cross-sectional study that included 602 patients with MS. 

Disclosures: The authors declared no conflicts of interest.

Citation: Nazari F et al. BMC Neurol. 2020 Jan 17. doi: 10.1186/s12883-019-1582-1. 

Serum levels of neurofilament light (NfL) are elevated as long as 6 years before the clinical onset of multiple sclerosis (MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.

Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
 

Researchers compared presymptomatic and symptomatic samples

With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.

Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.

Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
 

Levels were higher in cases than in controls

About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.

For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.

In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
 

Population included few women

“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.

The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.

The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.

[email protected]

SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.

Serum levels of neurofilament light (NfL) are elevated as long as 6 years before the clinical onset of multiple sclerosis (MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.

Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
 

Researchers compared presymptomatic and symptomatic samples

With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.

Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.

Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
 

Levels were higher in cases than in controls

About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.

For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.

In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
 

Population included few women

“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.

The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.

The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.

[email protected]

SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.

Serum levels of neurofilament light (NfL) are elevated as long as 6 years before the clinical onset of multiple sclerosis (MS), according to research published in the January issue of JAMA Neurology. These results lend weight to the idea that MS has a prodromal phase, and this phase appears to be associated with neurodegeneration, according to the authors.

Patients often have CNS lesions of various stages of development at the time of their first demyelinating event, and this finding was one basis for neurologists’ hypothesis of a prodromal phase of MS. The finding that one-third of patients with radiologically isolated syndrome develop MS within 5 years also lends credence to this idea. Diagnosing MS early would enable early treatment that could prevent demyelination and the progression of neurodegeneration.
 

Researchers compared presymptomatic and symptomatic samples

With this idea in mind, Kjetil Bjornevik, MD, PhD, a member of the neuroepidemiology research group at Harvard TH Chan School of Public Health in Boston, and colleagues evaluated whether serum levels of NfL, a marker of ongoing neuroaxonal degeneration, were increased in the years before and around the time of clinical onset of MS. For their study population, the investigators chose active-duty U.S. military personnel who have at least one serum sample stored in the U.S. Department of Defense Serum Repository. Samples are collected after routine HIV type 1 antibody testing.

Within this population, Dr. Bjornevik and colleagues identified patients with MS who had at least one presymptomatic serum sample. The date of clinical MS onset was defined as the date of the first neurologic symptoms attributable to MS documented in the medical record. The investigators randomly selected two control individuals from the population and matched them to each case by age, sex, race or ethnicity, and dates of sample collection. Eligible controls were on active duty on the date of onset of the matched case.

Dr. Bjornevik and colleagues identified 245 patients with MS. Among this sample, the researchers selected two groups that each included 30 cases and 30 controls. The first group included patients who had provided at least one serum sample before MS onset and one sample within 2 years after MS onset. The second group included cases with at least two presymptomatic serum samples, one of which was collected more than 5 years before MS diagnosis, and the other of which was collected between 2 and 5 years before diagnosis. The investigators handled pairs of serum samples in the same way and assayed them in the same batch. The order of the samples in each pair was arranged at random.
 

Levels were higher in cases than in controls

About 77% of the population was male. Sixty percent of participants were white, 28% were black, and 6.7% were Hispanic. The population’s mean age at first sample collection was approximately 27 years. Mean age at MS onset was approximately 31 years.

For patients who provided samples before and after the clinical onset of MS, serum NfL levels were higher than in matched controls at both points. Most patients who passed from the presymptomatic stage to the symptomatic stage had a significant increase in serum NfL level (i.e., from a median of 25.0 pg/mL to a median of 45.1 pg/mL). Serum NfL levels at the two time points in controls did not differ significantly. For any given patient, an increase in serum NfL level from the presymptomatic measurement to the symptomatic measurement was associated with an increased risk of MS.

In patients with two presymptomatic samples, serum NfL levels were significantly higher in both samples than in the corresponding samples from matched controls. In cases, the earlier sample was collected at a median of 6 years before clinical onset of MS, and the later sample was collected at a median of 1 year before clinical onset. The serum NfL levels increased significantly between the two points for cases (i.e., a median increase of 1.3 pg/mL per year), but there was no significant difference in serum NfL level between the two samples in controls. A within-patient increase in presymptomatic serum NfL level was associated with an increased risk of MS.
 

Population included few women

“Our study differs from previous studies on the prodromal phase of MS because these have used indirect markers of this phase, which included unspecific symptoms or disturbances occurring before the clinical onset, compared with a marker of neurodegeneration,” wrote Dr. Bjornevik and colleagues. Initiation of treatment with disease-modifying therapy is associated with reductions in serum NfL levels, and this association could explain why some patients in the current study had higher NfL levels before MS onset than afterward. Furthermore, serum NfL levels are highly associated with levels of NfL in cerebrospinal fluid. “Thus, our findings of a presymptomatic increase in serum NfL not only suggest the presence of a prodromal phase in MS, but also that this phase is associated with neurodegeneration,” wrote the investigators.

The study’s well-defined population helped to minimize selection bias, and the blinded, randomized method of analyzing the serum samples eliminated artifactual differences in serum NfL concentrations. But the small sample size precluded analyses that could have influenced clinical practice, wrote Dr. Bjornevik and colleagues. For example, the researchers could not evaluate distinct cutoffs in serum NfL level that could mark the beginning of the prodromal phase of MS. Nor could they determine whether presymptomatic serum NfL levels varied with age at clinical onset, sex, or race. The small number of women in the sample was another limitation of the study.

The Swiss National Research Foundation and the National Institute of Neurologic Disorders and Stroke funded the study. Several of the investigators received fees from various drug companies that were unrelated to the study, and one researcher received grants from the National Institutes of Health during the study.

[email protected]

SOURCE: Bjornevik K et al. JAMA Neurol. 2020;77(1):58-64.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

[email protected]

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

[email protected]

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.

Modafinil exposure during pregnancy was associated with an approximately tripled risk of congenital malformations in a large Danish registry-based study.

Modafinil (Provigil) is commonly prescribed to address daytime sleepiness in narcolepsy and multiple sclerosis. An interim postmarketing safety analysis showed increased rates of major malformation in modafinil-exposed pregnancies, so the manufacturer issued an alert advising health care professionals of this safety signal in June 2019, wrote Per Damkier, MD, PhD, corresponding author of a JAMA research letter reporting the Danish study results. The postmarketing study had shown a major malformation rate of about 15% in modafinil-exposed pregnancies, much higher than the 3% background rate.

Dr. Damkier and Anne Broe, MD, PhD, both of the department of clinical biochemistry and pharmacology at Odense (Denmark) University Hospital, compared outcomes for pregnant women who were prescribed modafinil at any point during the first trimester of pregnancy with those who were prescribed an active comparator, methylphenidate, as well as with those who had neither exposure. Methylphenidate is not associated with congenital malformations and is used for indications similar to modafinil.

Looking at all pregnancies for whom complete records existed in Danish health registries between 2004 and 2017, the investigators found 49 modafinil-exposed pregnancies, 963 methylphenidate-exposed pregnancies, and 828,644 pregnancies with neither exposure.

Six major congenital malformations occurred in the modafinil-exposed group for an absolute risk of 12%. Major malformations occurred in 43 (4.5%) of the methylphenidate-exposed group and 32,466 (3.9%) of the unexposed group.

Using the extensive data available in public registries, the authors were able to perform logistic regression to adjust for concomitant use of other psychotropic medication; comorbidities such as diabetes and hypertension; and demographic and anthropometric measures such as maternal age, smoking status, and body mass index.

After this statistical adjustment, the researchers found that modafinil exposure during the first trimester of pregnancy was associated with an odds ratio of 3.4 (95% confidence interval, 1.2-9.7) for major congenital malformation, compared with first-trimester methylphenidate exposure. Compared with the unexposed cohort, modafinil-exposed pregnancies had an adjusted odds ratio of 2.7 (95% CI, 1.1-6.9) for major congenital malformation.

A total of 13 (27%) women who took modafinil had multiple sclerosis, but the authors excluded women who’d received a prescription for the multiple sclerosis drug teriflunomide (Aubagio), a known teratogen. Sleep disorders were reported for 39% of modafinil users, compared with 4.5% of methylphenidate users. Rates of psychoactive drug use were 41% for the modafinil group and 30% for the methylphenidate group.

The authors acknowledged the possibility of residual confounders affecting their results, and of the statistical problems with the very small sample size of modafinil-exposed pregnancies. Also, actual medication use – rather than prescription redemption – wasn’t captured in the study.

The study was partially funded by the Novo Nordisk Foundation. The authors reported no conflicts of interest.

[email protected]

SOURCE: Damkier P, Broe A. JAMA. 2020;323(4):374-6.