Key clinical point: Higher serum concentrations of 25-hydroxyvitamin D (25(OH)D) are associated with a reduced risk for multiple sclerosis (MS).

Major finding: Being in the top 25(OH)D quintile was significantly associated with a reduced risk of multiple sclerosis (odds ratio, 0.68; 95% confidence interval, 0.50-0.93).

Study details: A nested case-control study using data from 6 Swedish biobanks (665 cases and an equal number of matched controls).

Disclosures: This study was supported by the Swedish Research Council and through a regional agreement between Umea University and the Vasterbotten County Council. One author received speaking fees from Merck-Serono and served on advisory boards for Merck-Serono and Biogen and another received honoraria for lectures from Genzyme and for advisory board roles from Roche and Novartis.

Citation: Biström M et al. Mult Scler J Exp Transl Clin. 2019 Dec 6. doi: 10.1177/2055217319892291.

Key clinical point: Higher serum concentrations of 25-hydroxyvitamin D (25(OH)D) are associated with a reduced risk for multiple sclerosis (MS).

Major finding: Being in the top 25(OH)D quintile was significantly associated with a reduced risk of multiple sclerosis (odds ratio, 0.68; 95% confidence interval, 0.50-0.93).

Study details: A nested case-control study using data from 6 Swedish biobanks (665 cases and an equal number of matched controls).

Disclosures: This study was supported by the Swedish Research Council and through a regional agreement between Umea University and the Vasterbotten County Council. One author received speaking fees from Merck-Serono and served on advisory boards for Merck-Serono and Biogen and another received honoraria for lectures from Genzyme and for advisory board roles from Roche and Novartis.

Citation: Biström M et al. Mult Scler J Exp Transl Clin. 2019 Dec 6. doi: 10.1177/2055217319892291.

Key clinical point: Higher serum concentrations of 25-hydroxyvitamin D (25(OH)D) are associated with a reduced risk for multiple sclerosis (MS).

Major finding: Being in the top 25(OH)D quintile was significantly associated with a reduced risk of multiple sclerosis (odds ratio, 0.68; 95% confidence interval, 0.50-0.93).

Study details: A nested case-control study using data from 6 Swedish biobanks (665 cases and an equal number of matched controls).

Disclosures: This study was supported by the Swedish Research Council and through a regional agreement between Umea University and the Vasterbotten County Council. One author received speaking fees from Merck-Serono and served on advisory boards for Merck-Serono and Biogen and another received honoraria for lectures from Genzyme and for advisory board roles from Roche and Novartis.

Citation: Biström M et al. Mult Scler J Exp Transl Clin. 2019 Dec 6. doi: 10.1177/2055217319892291.

Key clinical point: In patients with relapsing multiple sclerosis, fingolimod has a superior effect on clinical and magnetic resonance imaging (MRI) outcomes than placebo and presents an acceptable safety profile.

Major finding: Compared with placebo, fingolimod (0.5, 1.25, and 5 mg/day doses) had a significant reduction in annualized relapse rate. Fingolimod demonstrated beneficial effects on MRI outcomes, including the number of gadolinium-enhancing T1 lesions, and improved patient quality of life. No significant difference was found between the groups in terms of adverse events.

Study details: This was a systematic review and meta-analysis of 10 studies, including 6,547 participants.

Disclosures: The authors reported having no conflicts of interest.

Citation: Yang T et al. Br J Clin Pharmacol. 2019 Dec 23. doi: 10.1111/bcp.14198.

Key clinical point: In patients with relapsing multiple sclerosis, fingolimod has a superior effect on clinical and magnetic resonance imaging (MRI) outcomes than placebo and presents an acceptable safety profile.

Major finding: Compared with placebo, fingolimod (0.5, 1.25, and 5 mg/day doses) had a significant reduction in annualized relapse rate. Fingolimod demonstrated beneficial effects on MRI outcomes, including the number of gadolinium-enhancing T1 lesions, and improved patient quality of life. No significant difference was found between the groups in terms of adverse events.

Study details: This was a systematic review and meta-analysis of 10 studies, including 6,547 participants.

Disclosures: The authors reported having no conflicts of interest.

Citation: Yang T et al. Br J Clin Pharmacol. 2019 Dec 23. doi: 10.1111/bcp.14198.

Key clinical point: In patients with relapsing multiple sclerosis, fingolimod has a superior effect on clinical and magnetic resonance imaging (MRI) outcomes than placebo and presents an acceptable safety profile.

Major finding: Compared with placebo, fingolimod (0.5, 1.25, and 5 mg/day doses) had a significant reduction in annualized relapse rate. Fingolimod demonstrated beneficial effects on MRI outcomes, including the number of gadolinium-enhancing T1 lesions, and improved patient quality of life. No significant difference was found between the groups in terms of adverse events.

Study details: This was a systematic review and meta-analysis of 10 studies, including 6,547 participants.

Disclosures: The authors reported having no conflicts of interest.

Citation: Yang T et al. Br J Clin Pharmacol. 2019 Dec 23. doi: 10.1111/bcp.14198.

Key clinical point: The discontinuation of natalizumab (NTZ) therapy may lead to a marked reactivation of multiple sclerosis (MS); high disease activity and a high level of disability before NTZ initiation predicted multiple sclerosis reactivation.

Major finding: Clinical reactivation was reported in 20.2% of patients within 6 months after NTZ discontinuation. A higher number of relapses during the year before NTZ initiation was significantly associated with an increased risk of reactivation at 6 and 12 months. At 6 months, an Expanded Disability Status Scale (EDSS) of 5.5 or higher before NTZ initiation was associated with a higher reactivation risk.

Study details: The findings are based on the results of a retrospective study of 89 patients with MS who had discontinued NTZ treatment.

Disclosures: The study was in part supported by a VTR grant from Kuopio University Hospital and personal grants from Ilkka Rauma, MD, from Orion Research Foundation and The Finnish Medical Foundation.

Citation: Mustonen T BM et al. Mult Scler Relat Disord. 2019 Nov 5. doi: 10.1016/j.msard.2019.101498.

Key clinical point: The discontinuation of natalizumab (NTZ) therapy may lead to a marked reactivation of multiple sclerosis (MS); high disease activity and a high level of disability before NTZ initiation predicted multiple sclerosis reactivation.

Major finding: Clinical reactivation was reported in 20.2% of patients within 6 months after NTZ discontinuation. A higher number of relapses during the year before NTZ initiation was significantly associated with an increased risk of reactivation at 6 and 12 months. At 6 months, an Expanded Disability Status Scale (EDSS) of 5.5 or higher before NTZ initiation was associated with a higher reactivation risk.

Study details: The findings are based on the results of a retrospective study of 89 patients with MS who had discontinued NTZ treatment.

Disclosures: The study was in part supported by a VTR grant from Kuopio University Hospital and personal grants from Ilkka Rauma, MD, from Orion Research Foundation and The Finnish Medical Foundation.

Citation: Mustonen T BM et al. Mult Scler Relat Disord. 2019 Nov 5. doi: 10.1016/j.msard.2019.101498.

Key clinical point: The discontinuation of natalizumab (NTZ) therapy may lead to a marked reactivation of multiple sclerosis (MS); high disease activity and a high level of disability before NTZ initiation predicted multiple sclerosis reactivation.

Major finding: Clinical reactivation was reported in 20.2% of patients within 6 months after NTZ discontinuation. A higher number of relapses during the year before NTZ initiation was significantly associated with an increased risk of reactivation at 6 and 12 months. At 6 months, an Expanded Disability Status Scale (EDSS) of 5.5 or higher before NTZ initiation was associated with a higher reactivation risk.

Study details: The findings are based on the results of a retrospective study of 89 patients with MS who had discontinued NTZ treatment.

Disclosures: The study was in part supported by a VTR grant from Kuopio University Hospital and personal grants from Ilkka Rauma, MD, from Orion Research Foundation and The Finnish Medical Foundation.

Citation: Mustonen T BM et al. Mult Scler Relat Disord. 2019 Nov 5. doi: 10.1016/j.msard.2019.101498.

Key clinical point: Older age at onset and presence of clinical or radiological disease activity was found to correlate with disability progression in patients with primary progressive multiple sclerosis (MS).

Major finding: The analysis of age at onset showed that for every 10-year increase, the risk of reaching Expanded Disability Status Scale (EDSS) scores of 4 and 6 increased by 26% and 31%, respectively. Patients with clinical exacerbations reached EDSS scores of 6, 7, and 8 faster than those without associated exacerbations; patients with gadolinium-enhancing lesions reached EDSS scores of 7 earlier.

Study details: A retrospective study conducted at 2 multiple sclerosis clinics in Argentina that included 178 patients with a median age of MS onset of 42 years.

Disclosures: This study was partially financed by an unrestricted grant from Merck Argentina (JC) and supported by internal funds from the Neuroimmunology Department of Fleni. The corresponding author is a board member of Merck-Serono Argentina, Biogen-Idec LATAM, and Merck-Serono LATAM.

Citation: Marrodan M, et al. Mult Scler Relat Disord. 2019 Dec 14. doi: 10.1016/j.msard.2019.101892.

Key clinical point: Older age at onset and presence of clinical or radiological disease activity was found to correlate with disability progression in patients with primary progressive multiple sclerosis (MS).

Major finding: The analysis of age at onset showed that for every 10-year increase, the risk of reaching Expanded Disability Status Scale (EDSS) scores of 4 and 6 increased by 26% and 31%, respectively. Patients with clinical exacerbations reached EDSS scores of 6, 7, and 8 faster than those without associated exacerbations; patients with gadolinium-enhancing lesions reached EDSS scores of 7 earlier.

Study details: A retrospective study conducted at 2 multiple sclerosis clinics in Argentina that included 178 patients with a median age of MS onset of 42 years.

Disclosures: This study was partially financed by an unrestricted grant from Merck Argentina (JC) and supported by internal funds from the Neuroimmunology Department of Fleni. The corresponding author is a board member of Merck-Serono Argentina, Biogen-Idec LATAM, and Merck-Serono LATAM.

Citation: Marrodan M, et al. Mult Scler Relat Disord. 2019 Dec 14. doi: 10.1016/j.msard.2019.101892.

Key clinical point: Older age at onset and presence of clinical or radiological disease activity was found to correlate with disability progression in patients with primary progressive multiple sclerosis (MS).

Major finding: The analysis of age at onset showed that for every 10-year increase, the risk of reaching Expanded Disability Status Scale (EDSS) scores of 4 and 6 increased by 26% and 31%, respectively. Patients with clinical exacerbations reached EDSS scores of 6, 7, and 8 faster than those without associated exacerbations; patients with gadolinium-enhancing lesions reached EDSS scores of 7 earlier.

Study details: A retrospective study conducted at 2 multiple sclerosis clinics in Argentina that included 178 patients with a median age of MS onset of 42 years.

Disclosures: This study was partially financed by an unrestricted grant from Merck Argentina (JC) and supported by internal funds from the Neuroimmunology Department of Fleni. The corresponding author is a board member of Merck-Serono Argentina, Biogen-Idec LATAM, and Merck-Serono LATAM.

Citation: Marrodan M, et al. Mult Scler Relat Disord. 2019 Dec 14. doi: 10.1016/j.msard.2019.101892.

Key clinical point: Poor sleep and sleep disorders are prevalent in patients with mild to moderately severe multiple sclerosis (MS) and are associated with other comorbidities.

Main finding: Poor sleep was reported in 66% of patients with MS, sleep apnea in 31%, insomnia in 29%, and restless legs in 26%. Poor sleep and insomnia were independent predictors of fatigue (odds ratio, 2.63; P = .046) and depression (odds ratio, 5.62; P = .003), respectively.

Study details: A sleep substudy of a randomized controlled trial, including 111 adults with MS and an expanded disability status scale score between 2 and 6.

Disclosures: The study was supported by a grant from the National Health and Medical Research Council-Motor Impairment Program.

Citation: Hensen HA, et al. Sleep Med. 2019 Dec 16. doi: 10.1016/j.sleep.2019.11.415.

Key clinical point: Poor sleep and sleep disorders are prevalent in patients with mild to moderately severe multiple sclerosis (MS) and are associated with other comorbidities.

Main finding: Poor sleep was reported in 66% of patients with MS, sleep apnea in 31%, insomnia in 29%, and restless legs in 26%. Poor sleep and insomnia were independent predictors of fatigue (odds ratio, 2.63; P = .046) and depression (odds ratio, 5.62; P = .003), respectively.

Study details: A sleep substudy of a randomized controlled trial, including 111 adults with MS and an expanded disability status scale score between 2 and 6.

Disclosures: The study was supported by a grant from the National Health and Medical Research Council-Motor Impairment Program.

Citation: Hensen HA, et al. Sleep Med. 2019 Dec 16. doi: 10.1016/j.sleep.2019.11.415.

Key clinical point: Poor sleep and sleep disorders are prevalent in patients with mild to moderately severe multiple sclerosis (MS) and are associated with other comorbidities.

Main finding: Poor sleep was reported in 66% of patients with MS, sleep apnea in 31%, insomnia in 29%, and restless legs in 26%. Poor sleep and insomnia were independent predictors of fatigue (odds ratio, 2.63; P = .046) and depression (odds ratio, 5.62; P = .003), respectively.

Study details: A sleep substudy of a randomized controlled trial, including 111 adults with MS and an expanded disability status scale score between 2 and 6.

Disclosures: The study was supported by a grant from the National Health and Medical Research Council-Motor Impairment Program.

Citation: Hensen HA, et al. Sleep Med. 2019 Dec 16. doi: 10.1016/j.sleep.2019.11.415.

Key clinical point: Learning a second language may increase the grey matter volume in patients with multiple sclerosis (MS) and consequently improve mental health and health-related quality of life.

Major finding: Training in a second language was associated with a significant increase of grey matter volume in the right hippocampus, parahippocampus, and putamen region of the brain in patients with MS.

Study details: A prospective evaluation of second language training in patients with MS (n = 11) and healthy controls (n = 12).

Disclosures: The study was funded by Merck Austria, without any other external funding. None of the authors was affiliated with Merck Austria.

Citation: Ehling R, et al. PLoS One. 2019 Dec 23. doi: 10.1371/journal.pone.0226525.

Key clinical point: Learning a second language may increase the grey matter volume in patients with multiple sclerosis (MS) and consequently improve mental health and health-related quality of life.

Major finding: Training in a second language was associated with a significant increase of grey matter volume in the right hippocampus, parahippocampus, and putamen region of the brain in patients with MS.

Study details: A prospective evaluation of second language training in patients with MS (n = 11) and healthy controls (n = 12).

Disclosures: The study was funded by Merck Austria, without any other external funding. None of the authors was affiliated with Merck Austria.

Citation: Ehling R, et al. PLoS One. 2019 Dec 23. doi: 10.1371/journal.pone.0226525.

Key clinical point: Learning a second language may increase the grey matter volume in patients with multiple sclerosis (MS) and consequently improve mental health and health-related quality of life.

Major finding: Training in a second language was associated with a significant increase of grey matter volume in the right hippocampus, parahippocampus, and putamen region of the brain in patients with MS.

Study details: A prospective evaluation of second language training in patients with MS (n = 11) and healthy controls (n = 12).

Disclosures: The study was funded by Merck Austria, without any other external funding. None of the authors was affiliated with Merck Austria.

Citation: Ehling R, et al. PLoS One. 2019 Dec 23. doi: 10.1371/journal.pone.0226525.

Key clinical point: Dalfampridine may be a treatment option for balance impairment associated with multiple sclerosis (MS).

Major finding: The dalfampridine treated group demonstrated better balance in both single- (quiet standing test) and dual-task (Stroop test) conditions than the placebo group; however, the benefits of dalfampridine were not retained beyond 4 weeks after discontinuation of treatment.

Study details: A substudy of a randomized, double-blind, placebo-controlled trial in which patients received dalfampridine 10 mg (27 patients) or placebo (14 patients) twice a day for 12 weeks.

Disclosures: The original trial was funded by Biogen. The corresponding author disclosed consultancy with Almirall, Biogen, Novartis, Genzyme, Roche, and Teva and research funding from Associazione Italiana Sclerosi Multipla and Genzyme.

Citation: Prosperini L, et al. Neurotherapeutics. 2019 Dec 9. doi: 10.1007/s13311-019-00813-5.

Key clinical point: Dalfampridine may be a treatment option for balance impairment associated with multiple sclerosis (MS).

Major finding: The dalfampridine treated group demonstrated better balance in both single- (quiet standing test) and dual-task (Stroop test) conditions than the placebo group; however, the benefits of dalfampridine were not retained beyond 4 weeks after discontinuation of treatment.

Study details: A substudy of a randomized, double-blind, placebo-controlled trial in which patients received dalfampridine 10 mg (27 patients) or placebo (14 patients) twice a day for 12 weeks.

Disclosures: The original trial was funded by Biogen. The corresponding author disclosed consultancy with Almirall, Biogen, Novartis, Genzyme, Roche, and Teva and research funding from Associazione Italiana Sclerosi Multipla and Genzyme.

Citation: Prosperini L, et al. Neurotherapeutics. 2019 Dec 9. doi: 10.1007/s13311-019-00813-5.

Key clinical point: Dalfampridine may be a treatment option for balance impairment associated with multiple sclerosis (MS).

Major finding: The dalfampridine treated group demonstrated better balance in both single- (quiet standing test) and dual-task (Stroop test) conditions than the placebo group; however, the benefits of dalfampridine were not retained beyond 4 weeks after discontinuation of treatment.

Study details: A substudy of a randomized, double-blind, placebo-controlled trial in which patients received dalfampridine 10 mg (27 patients) or placebo (14 patients) twice a day for 12 weeks.

Disclosures: The original trial was funded by Biogen. The corresponding author disclosed consultancy with Almirall, Biogen, Novartis, Genzyme, Roche, and Teva and research funding from Associazione Italiana Sclerosi Multipla and Genzyme.

Citation: Prosperini L, et al. Neurotherapeutics. 2019 Dec 9. doi: 10.1007/s13311-019-00813-5.

Key clinical point: Low sun exposure increases the risk of multiple sclerosis (MS) both directly and indirectly, which impacts vitamin D levels. Low sun exposure and vitamin D deficiency may be different risk factors acting synergistically.

Major finding: Low exposure to sunlight was associated with a 26% and 10% higher risk for MS through direct and indirect effects on the vitamin D levels, respectively. About 30% of the total effect of low sun exposure-related MS risk was mediated by vitamin D deficiency.

Study details: The data were obtained from two population-based case–control studies (7,069 cases; 6,632 matched controls).

Disclosures: The research was supported by grants received from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, and the Swedish Society for Medical Research. Some of the investigators reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Hedström AK, et al. J Neurol. 2019 Dec 12. doi: 10.1007/s00415-019-09677-3.

Key clinical point: Low sun exposure increases the risk of multiple sclerosis (MS) both directly and indirectly, which impacts vitamin D levels. Low sun exposure and vitamin D deficiency may be different risk factors acting synergistically.

Major finding: Low exposure to sunlight was associated with a 26% and 10% higher risk for MS through direct and indirect effects on the vitamin D levels, respectively. About 30% of the total effect of low sun exposure-related MS risk was mediated by vitamin D deficiency.

Study details: The data were obtained from two population-based case–control studies (7,069 cases; 6,632 matched controls).

Disclosures: The research was supported by grants received from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, and the Swedish Society for Medical Research. Some of the investigators reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Hedström AK, et al. J Neurol. 2019 Dec 12. doi: 10.1007/s00415-019-09677-3.

Key clinical point: Low sun exposure increases the risk of multiple sclerosis (MS) both directly and indirectly, which impacts vitamin D levels. Low sun exposure and vitamin D deficiency may be different risk factors acting synergistically.

Major finding: Low exposure to sunlight was associated with a 26% and 10% higher risk for MS through direct and indirect effects on the vitamin D levels, respectively. About 30% of the total effect of low sun exposure-related MS risk was mediated by vitamin D deficiency.

Study details: The data were obtained from two population-based case–control studies (7,069 cases; 6,632 matched controls).

Disclosures: The research was supported by grants received from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, and the Swedish Society for Medical Research. Some of the investigators reported receiving grants and personal fees from multiple pharmaceutical companies.

Citation: Hedström AK, et al. J Neurol. 2019 Dec 12. doi: 10.1007/s00415-019-09677-3.

Key clinical point: Breastfeeding may prevent postpartum relapses in women with multiple sclerosis (MS). Major finding: Women with MS who breastfed had a 37% lower risk of postpartum relapse, compared with those who did not breastfeed (P = .006); exclusive breastfeeding had a greater benefit than nonexclusive breastfeeding.

Study details: A systematic review and meta-analysis of 24 studies, including 2,974 women.

Disclosures: The National Multiple Sclerosis Society supported the study through a Sylvia Lawry Physician Fellowship awarded to Dr. Krysko.

Citation: Krysko KM, et al. JAMA Neurol. 2019 Dec 9. doi: 10.1001/jamaneurol.2019.4173.

Key clinical point: Breastfeeding may prevent postpartum relapses in women with multiple sclerosis (MS). Major finding: Women with MS who breastfed had a 37% lower risk of postpartum relapse, compared with those who did not breastfeed (P = .006); exclusive breastfeeding had a greater benefit than nonexclusive breastfeeding.

Study details: A systematic review and meta-analysis of 24 studies, including 2,974 women.

Disclosures: The National Multiple Sclerosis Society supported the study through a Sylvia Lawry Physician Fellowship awarded to Dr. Krysko.

Citation: Krysko KM, et al. JAMA Neurol. 2019 Dec 9. doi: 10.1001/jamaneurol.2019.4173.

Key clinical point: Breastfeeding may prevent postpartum relapses in women with multiple sclerosis (MS). Major finding: Women with MS who breastfed had a 37% lower risk of postpartum relapse, compared with those who did not breastfeed (P = .006); exclusive breastfeeding had a greater benefit than nonexclusive breastfeeding.

Study details: A systematic review and meta-analysis of 24 studies, including 2,974 women.

Disclosures: The National Multiple Sclerosis Society supported the study through a Sylvia Lawry Physician Fellowship awarded to Dr. Krysko.

Citation: Krysko KM, et al. JAMA Neurol. 2019 Dec 9. doi: 10.1001/jamaneurol.2019.4173.

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.