Heidi Splete

Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.

“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.

In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.

After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.

In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.

The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.

The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.

The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.

However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.

AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.

SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.

Treatment with subcutaneous treprostinil significantly improved exercise capacity in patients with severe chronic thromboembolic pulmonary hypertension, a study based on data from 105 adults has shown.

goa_novi/ThinkStock

Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.

The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.

Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.

The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.

In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.

Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.

The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.

The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.

SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.

Treatment with subcutaneous treprostinil significantly improved exercise capacity in patients with severe chronic thromboembolic pulmonary hypertension, a study based on data from 105 adults has shown.

goa_novi/ThinkStock

Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.

The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.

Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.

The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.

In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.

Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.

The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.

The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.

SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.

Treatment with subcutaneous treprostinil significantly improved exercise capacity in patients with severe chronic thromboembolic pulmonary hypertension, a study based on data from 105 adults has shown.

goa_novi/ThinkStock

Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.

The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.

Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.

The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.

In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.

Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.

The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.

The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.

SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.

Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.

“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.

The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.

Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.

Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.

Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.

At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.

Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.

Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).

“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.

The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.

“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.

“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.

The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.

SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.

Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.

“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.

The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.

Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.

Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.

Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.

At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.

Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.

Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).

“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.

The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.

“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.

“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.

The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.

SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.

Accelerated knee osteoarthritis is characterized by distinct features that include destabilizing meniscal tears in two or more areas as well as other pathologies, based on data from the Osteoarthritis Initiative.

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The possibility of accelerated knee osteoarthritis (AKOA) as a unique subset of knee osteoarthritis has not been well studied, wrote Jeffrey B. Driban, PhD, of Tufts University, Boston, and his colleagues.

“If specific pathologies differentiate people at risk for AKOA it may help identify adults with early-stage or high-risk for AKOA and inspire novel prevention strategies,” they wrote in their report, published in Arthritis & Rheumatology.

The researchers reviewed data from three groups of adults selected from participants in the Osteoarthritis Initiative, a cohort of 4,796 adults with KOA or at risk for symptomatic KOA who were recruited at four clinical sites in the United States. These groups included 125 with AKOA, 125 with typical knee osteoarthritis (KOA), and 125 without knee OA.

Overall, patients with AKOA were approximately seven times more likely than were patients with KOA to have destabilizing meniscal tears in two or more areas at the time of the index visit (42% vs. 14%); less than 5% of adults with no KOA experienced destabilizing meniscal tears. In addition, patients with AKOA were more than four times as likely to have miscellaneous pathology starting the year before the index visit, compared with those without AKOA.

Approximately 63% of the participants in each group were women, and the majority were overweight. The average age, weight, and global impact of arthritis were greater in the AKOA group when compared against the typical KOA and no-KOA groups.

Participants were assessed via MRI reviewed by radiologists who were blinded to the groups.

At the index visit, 49% of adults with AKOA had either a destabilizing meniscal tear or miscellaneous pathology, compared with 15% of adults with KOA and 6% of adults without KOA.

Adults with AKOA also showed significantly greater cartilage loss prior to the index visit in comparison with typical KOA patients, and AKOA patients had less cartilage in the medial and lateral tibia and medial femur, compared with adults who had typical KOA or no KOA after the index visit.

Adults who developed AKOA showed a significantly higher bone marrow lesion volume when compared against the typical KOA and no-KOA groups at 1 year prior to the index visit, and their bone marrow lesion volume increased on average 13 times more compared with typical KOA patients over the 2 years before the index visit, the researchers noted (2.00 mL vs. 0.15 mL, respectively).

“These findings add to the evidence that AKOA is different [from] the typically perceived archetype of slow-progressing osteoarthritis” with a unique risk profile, the researchers said.

The study findings were limited by several factors, including the relatively small sample size, uncertain timing of disease onset, a potentially limited definition of a destabilizing meniscal tear (defined as a root tear, radial tear, or complex tear, which almost always featured a radial component), a lack of a universal AKOA pathology, and some missing MRI data, the researchers noted. However, the results support previous studies suggesting a link between meniscal pathology and increased risk for AKOA, they said.

“It is important to acknowledge that it remains unclear if AKOA has any relation to type 2 rapidly progressive osteoarthritis, which was characterized by a more dramatic joint space narrowing (2 mm or more within 1 year) and greater abnormal bone loss/destruction,” they noted.

“Future research with a larger sample size of adults at risk for AKOA may help further refine our understanding of AKOA and help develop a clinically useful predictive model,” they added.

The study was supported in part by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and private funding included Merck, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no financial conflicts to disclose.

SOURCE: Driban JB et al. Arthritis Rheumatol. 2018 Dec 28. doi: 10.1002/art.40826.

Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.

Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.

The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.

Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.

A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.

The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.

“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.

However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.

The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.

SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.

Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.

Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.

The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.

Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.

A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.

The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.

“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.

However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.

The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.

SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.

Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.

Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.

The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.

Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.

A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.

The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.

“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.

However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.

The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.

SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.

Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.

In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).

In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.

The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.

However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.

The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.

SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.

Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.

In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).

In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.

The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.

However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.

The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.

SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.

Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.

In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).

In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.

The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.

However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.

The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.

SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.

“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.

In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.

Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.

The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.

The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.

SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.

Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.

“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.

In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.

Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.

The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.

The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.

SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.

Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.

“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.

In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.

Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.

The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.

The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.

SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.

Tofacitinib significantly improved skin lesions associated with cutaneous sarcoidosis, according to a case report published in the New England Journal of Medicine.

Treatment options for cutaneous sarcoidosis are limited, as are data on the effectiveness of alternatives to prednisone, which is often the first choice despite adverse effects, wrote William Damsky, MD, of Yale University in New Haven, Conn., and his colleagues.

Previous studies have suggested involvement of the JAK-STAT pathway in sarcoidosis; therefore, the researchers treated a patient who had refractory cutaneous sarcoidosis with oral tofacitinib. The treatment significantly improved the patient’s skin lesions both clinically and histologically.

The patient was a 48-year-old woman with a history of cutaneous and pulmonary sarcoidosis and treatment-resistant skin lesions. At the time of the case report, she had no pulmonary symptoms and no ophthalmologic issues, but presented with pink-brown indurated papules and plaques, and some alopecia on her scalp (N Engl J Med. 2018;379:2540-6).

The patient had not responded to other medications including glucocorticoids, minocycline, hydroxychloroquine, methotrexate, adalimumab, tacrolimus, and apremilast. With her consent, the patient received off-label tofacitinib at 5 mg twice daily. The lesions began to improve, but treatment was discontinued because of insurance issues. When treatment resumed, the patient’s Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score, used to assess disease activity, was 85 on a scale of 0 to 165; this score dropped to 53 after 4 months of treatment.

In addition, two samples collected after 10 months of treatment showed histologic resolution of granulomas.

Although the findings must be replicated in other patients, the results suggest that “the dysregulation of JAK-STAT–dependent cytokines (e.g., interferon-gamma) is pathogenically involved in cutaneous sarcoidosis and, probably, in sarcoidosis in general,” the researchers said.

Dr. Damsky disclosed a financial relationship with Eli Lilly, and research funding from the Dermatology Foundation and the National Institutes of Health. The study was supported by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research, the National Institutes of Health, and the Dermatology Foundation.
 

SOURCE: Damsky W et al. N Engl J Med. 2018;379:2540-6.

Tofacitinib significantly improved skin lesions associated with cutaneous sarcoidosis, according to a case report published in the New England Journal of Medicine.

Treatment options for cutaneous sarcoidosis are limited, as are data on the effectiveness of alternatives to prednisone, which is often the first choice despite adverse effects, wrote William Damsky, MD, of Yale University in New Haven, Conn., and his colleagues.

Previous studies have suggested involvement of the JAK-STAT pathway in sarcoidosis; therefore, the researchers treated a patient who had refractory cutaneous sarcoidosis with oral tofacitinib. The treatment significantly improved the patient’s skin lesions both clinically and histologically.

The patient was a 48-year-old woman with a history of cutaneous and pulmonary sarcoidosis and treatment-resistant skin lesions. At the time of the case report, she had no pulmonary symptoms and no ophthalmologic issues, but presented with pink-brown indurated papules and plaques, and some alopecia on her scalp (N Engl J Med. 2018;379:2540-6).

The patient had not responded to other medications including glucocorticoids, minocycline, hydroxychloroquine, methotrexate, adalimumab, tacrolimus, and apremilast. With her consent, the patient received off-label tofacitinib at 5 mg twice daily. The lesions began to improve, but treatment was discontinued because of insurance issues. When treatment resumed, the patient’s Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score, used to assess disease activity, was 85 on a scale of 0 to 165; this score dropped to 53 after 4 months of treatment.

In addition, two samples collected after 10 months of treatment showed histologic resolution of granulomas.

Although the findings must be replicated in other patients, the results suggest that “the dysregulation of JAK-STAT–dependent cytokines (e.g., interferon-gamma) is pathogenically involved in cutaneous sarcoidosis and, probably, in sarcoidosis in general,” the researchers said.

Dr. Damsky disclosed a financial relationship with Eli Lilly, and research funding from the Dermatology Foundation and the National Institutes of Health. The study was supported by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research, the National Institutes of Health, and the Dermatology Foundation.
 

SOURCE: Damsky W et al. N Engl J Med. 2018;379:2540-6.

Tofacitinib significantly improved skin lesions associated with cutaneous sarcoidosis, according to a case report published in the New England Journal of Medicine.

Treatment options for cutaneous sarcoidosis are limited, as are data on the effectiveness of alternatives to prednisone, which is often the first choice despite adverse effects, wrote William Damsky, MD, of Yale University in New Haven, Conn., and his colleagues.

Previous studies have suggested involvement of the JAK-STAT pathway in sarcoidosis; therefore, the researchers treated a patient who had refractory cutaneous sarcoidosis with oral tofacitinib. The treatment significantly improved the patient’s skin lesions both clinically and histologically.

The patient was a 48-year-old woman with a history of cutaneous and pulmonary sarcoidosis and treatment-resistant skin lesions. At the time of the case report, she had no pulmonary symptoms and no ophthalmologic issues, but presented with pink-brown indurated papules and plaques, and some alopecia on her scalp (N Engl J Med. 2018;379:2540-6).

The patient had not responded to other medications including glucocorticoids, minocycline, hydroxychloroquine, methotrexate, adalimumab, tacrolimus, and apremilast. With her consent, the patient received off-label tofacitinib at 5 mg twice daily. The lesions began to improve, but treatment was discontinued because of insurance issues. When treatment resumed, the patient’s Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score, used to assess disease activity, was 85 on a scale of 0 to 165; this score dropped to 53 after 4 months of treatment.

In addition, two samples collected after 10 months of treatment showed histologic resolution of granulomas.

Although the findings must be replicated in other patients, the results suggest that “the dysregulation of JAK-STAT–dependent cytokines (e.g., interferon-gamma) is pathogenically involved in cutaneous sarcoidosis and, probably, in sarcoidosis in general,” the researchers said.

Dr. Damsky disclosed a financial relationship with Eli Lilly, and research funding from the Dermatology Foundation and the National Institutes of Health. The study was supported by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research, the National Institutes of Health, and the Dermatology Foundation.
 

SOURCE: Damsky W et al. N Engl J Med. 2018;379:2540-6.

U.S. Surgeon General Jerome Adams, MD, responded Dec. 18 to recent data showing a sharp increase in the use of nicotine-based e-cigarette products among American teens with an urgent call to action.

“I, Surgeon General of the United States Public Health Service, [Vice Admiral] Jerome Adams, am emphasizing the importance of protecting our children from a lifetime of nicotine addiction and associated health risks by immediately addressing the epidemic of youth e-cigarette use,” Dr. Adams said in an advisory. “The recent surge in e-cigarette use among youth, which has been fueled by new types of e-cigarettes that have recently entered the market, is a cause for great concern. We must take action now to protect the health of our nation’s young people.”

The surgeon general’s advisory emphasized that e-cigarette products are not harmless and that, in addition to potentially addictive nicotine, many products contain other dangerous substances, including heavy metals, volatile organic compounds, and ultrafine particles that can affect the lungs. In addition, some e-cigarette products contain potentially harmful chemicals used to add flavoring.

The complete advisory includes information for parents, teachers, and clinicians about the details of current e-cigarette products and strategies for working to reduce their use among teens.

The American Medical Association expressed support of the surgeon general’s call to action.

“The only way to prevent another generation from developing nicotine dependence is to continue to raise awareness that e-cigarettes are harmful, powerfully addictive, and can often lead young people to smoke conventional cigarettes. E-cigarettes have the potential to undermine the public health gains that have been made over the years in combating the smoking epidemic,” Barbara L. McAneny, MD, president of the AMA, said in the statement.

“Recognizing the use of e-cigarettes and vaping as an urgent public health epidemic, the AMA has adopted numerous policies in recent years aimed at preventing youth access to these harmful tobacco products. In line with the surgeon general’s advisory, the AMA also has existing policy urging physicians to educate themselves about e-cigarettes and be prepared to counsel patients about e-cigarette usage and the potential for nicotine addiction,” Dr. McAneny said. The AMA is working with the Food and Drug Administration to curb the marketing of e-cigarettes and other vaping products to individuals younger than 21 years, she added.

The American Heart Association expressed support for the surgeon general’s call as well.

“That the U.S. Surgeon General is calling teen vaping an ‘epidemic’ should seize the attention of elected officials and the community of organizations working to protect the health of our nation’s children. We commend Surgeon General Adams, Commissioner [Adam] Gottlieb and Secretary [Alex M.] Azar for marshaling parents, educators, health providers, and communities to apply proven methods to overcome the epidemic of e-cigarette use,” Nancy Brown, CEO of the AHA, said in a Dec. 18 statement.

“But more must be done in the face of rapidly rising e-cigarette use among youth. The FDA’s recent announcement that it plans to restrict marketing and sales of flavored tobacco products must be followed by immediate, concrete action that sends an unmistakable message that the tobacco industry’s relentless targeting of our nation’s children will no longer be tolerated,” she emphasized.

View the surgeon general’s video message and access additional e-cigarette information here.

U.S. Surgeon General Jerome Adams, MD, responded Dec. 18 to recent data showing a sharp increase in the use of nicotine-based e-cigarette products among American teens with an urgent call to action.

“I, Surgeon General of the United States Public Health Service, [Vice Admiral] Jerome Adams, am emphasizing the importance of protecting our children from a lifetime of nicotine addiction and associated health risks by immediately addressing the epidemic of youth e-cigarette use,” Dr. Adams said in an advisory. “The recent surge in e-cigarette use among youth, which has been fueled by new types of e-cigarettes that have recently entered the market, is a cause for great concern. We must take action now to protect the health of our nation’s young people.”

The surgeon general’s advisory emphasized that e-cigarette products are not harmless and that, in addition to potentially addictive nicotine, many products contain other dangerous substances, including heavy metals, volatile organic compounds, and ultrafine particles that can affect the lungs. In addition, some e-cigarette products contain potentially harmful chemicals used to add flavoring.

The complete advisory includes information for parents, teachers, and clinicians about the details of current e-cigarette products and strategies for working to reduce their use among teens.

The American Medical Association expressed support of the surgeon general’s call to action.

“The only way to prevent another generation from developing nicotine dependence is to continue to raise awareness that e-cigarettes are harmful, powerfully addictive, and can often lead young people to smoke conventional cigarettes. E-cigarettes have the potential to undermine the public health gains that have been made over the years in combating the smoking epidemic,” Barbara L. McAneny, MD, president of the AMA, said in the statement.

“Recognizing the use of e-cigarettes and vaping as an urgent public health epidemic, the AMA has adopted numerous policies in recent years aimed at preventing youth access to these harmful tobacco products. In line with the surgeon general’s advisory, the AMA also has existing policy urging physicians to educate themselves about e-cigarettes and be prepared to counsel patients about e-cigarette usage and the potential for nicotine addiction,” Dr. McAneny said. The AMA is working with the Food and Drug Administration to curb the marketing of e-cigarettes and other vaping products to individuals younger than 21 years, she added.

The American Heart Association expressed support for the surgeon general’s call as well.

“That the U.S. Surgeon General is calling teen vaping an ‘epidemic’ should seize the attention of elected officials and the community of organizations working to protect the health of our nation’s children. We commend Surgeon General Adams, Commissioner [Adam] Gottlieb and Secretary [Alex M.] Azar for marshaling parents, educators, health providers, and communities to apply proven methods to overcome the epidemic of e-cigarette use,” Nancy Brown, CEO of the AHA, said in a Dec. 18 statement.

“But more must be done in the face of rapidly rising e-cigarette use among youth. The FDA’s recent announcement that it plans to restrict marketing and sales of flavored tobacco products must be followed by immediate, concrete action that sends an unmistakable message that the tobacco industry’s relentless targeting of our nation’s children will no longer be tolerated,” she emphasized.

View the surgeon general’s video message and access additional e-cigarette information here.

U.S. Surgeon General Jerome Adams, MD, responded Dec. 18 to recent data showing a sharp increase in the use of nicotine-based e-cigarette products among American teens with an urgent call to action.

“I, Surgeon General of the United States Public Health Service, [Vice Admiral] Jerome Adams, am emphasizing the importance of protecting our children from a lifetime of nicotine addiction and associated health risks by immediately addressing the epidemic of youth e-cigarette use,” Dr. Adams said in an advisory. “The recent surge in e-cigarette use among youth, which has been fueled by new types of e-cigarettes that have recently entered the market, is a cause for great concern. We must take action now to protect the health of our nation’s young people.”

The surgeon general’s advisory emphasized that e-cigarette products are not harmless and that, in addition to potentially addictive nicotine, many products contain other dangerous substances, including heavy metals, volatile organic compounds, and ultrafine particles that can affect the lungs. In addition, some e-cigarette products contain potentially harmful chemicals used to add flavoring.

The complete advisory includes information for parents, teachers, and clinicians about the details of current e-cigarette products and strategies for working to reduce their use among teens.

The American Medical Association expressed support of the surgeon general’s call to action.

“The only way to prevent another generation from developing nicotine dependence is to continue to raise awareness that e-cigarettes are harmful, powerfully addictive, and can often lead young people to smoke conventional cigarettes. E-cigarettes have the potential to undermine the public health gains that have been made over the years in combating the smoking epidemic,” Barbara L. McAneny, MD, president of the AMA, said in the statement.

“Recognizing the use of e-cigarettes and vaping as an urgent public health epidemic, the AMA has adopted numerous policies in recent years aimed at preventing youth access to these harmful tobacco products. In line with the surgeon general’s advisory, the AMA also has existing policy urging physicians to educate themselves about e-cigarettes and be prepared to counsel patients about e-cigarette usage and the potential for nicotine addiction,” Dr. McAneny said. The AMA is working with the Food and Drug Administration to curb the marketing of e-cigarettes and other vaping products to individuals younger than 21 years, she added.

The American Heart Association expressed support for the surgeon general’s call as well.

“That the U.S. Surgeon General is calling teen vaping an ‘epidemic’ should seize the attention of elected officials and the community of organizations working to protect the health of our nation’s children. We commend Surgeon General Adams, Commissioner [Adam] Gottlieb and Secretary [Alex M.] Azar for marshaling parents, educators, health providers, and communities to apply proven methods to overcome the epidemic of e-cigarette use,” Nancy Brown, CEO of the AHA, said in a Dec. 18 statement.

“But more must be done in the face of rapidly rising e-cigarette use among youth. The FDA’s recent announcement that it plans to restrict marketing and sales of flavored tobacco products must be followed by immediate, concrete action that sends an unmistakable message that the tobacco industry’s relentless targeting of our nation’s children will no longer be tolerated,” she emphasized.

View the surgeon general’s video message and access additional e-cigarette information here.

Teenage use of vaping devices jumped significantly in the past year, with 37% of 12th-grade students reporting any vaping in 2018, compared with 28% in 2017, data announced Dec. 17 from the 2018 Monitoring the Future survey show.

LiudmylaSupynska/Thinkstock

In particular, nicotine vaping use in the 30 days prior to the survey nearly doubled among high school seniors, from approximately 11% in 2017 to 21% in 2018. Nicotine vaping also increased by 7.9% (from 8.2% to 16.1%) among 10th graders and by 2.6% (from 3.5% to 6.1%) among 8th graders, according to the survey results.

Vaping involves using a device such as an e-cigarette to inhale a heated aerosol product that usually contains nicotine but can be used to administer other types of drugs, said Nora D. Volkow, MD, director of the National Institute on Drug Abuse at the National Institutes of Health, in a press conference announcing the findings.

The increased prevalence of nicotine vaping in 10th and 12th graders is the largest annual increase in use of any substance recorded by Monitoring the Future, said Richard A. Miech, PhD, MPH, of the Institute for Social Research at the University of Michigan, Ann Arbor, and the principal survey investigator. “Something about this delivery device of vaping seems to really appeal to kids,” he said. The flavorings, concealability of the devices (which can be about the size of a flash drive), and ease of use seem to be contributing to the popularity of vaping, Dr. Miech added.

In addition, marijuana vaping increased significantly across all three grade levels in 2018 from 2017. Within 30 days of the survey, marijuana vaping increased from 4.9% to 7.5% in 12th graders, from 4.3% to 7.0% in 10th graders, and from 1.6% to 2.6% in 8th graders.

A take-home message for clinicians is the need to emphasize to teens that “vaping is not innocuous and not harmless,” said Dr. Miech in a question-and-answer session. Of note, data from multiple studies show that children who vape are about five times more likely to smoke cigarettes, he said.

The vaping devices are manufactured to deliver drugs into the lungs and ultimately high concentrations into the brain – which suggests the use of vaping devices to deliver other types of drugs might increase in the future, Dr. Volkow added.

Use of most other substances, including inhalants, heroin, cocaine, ecstasy, overall marijuana use, alcohol use, and extreme binge drinking remained stable, the researchers said. Cigarette smoking declined slightly among 12th graders but did not change significantly among 8th or 10th graders. Use of prescription opioids and tranquilizers declined in 2018 across all age groups.

“Vaping is reversing hard-fought declines in the number of adolescents who use nicotine,” Dr. Miech said in the news release announcing the results. “These results suggest that vaping is leading youth into nicotine use and nicotine addiction, not away from it.”

The data on vaping and nicotine use among American teens were published in a letter (N Engl J Med. 2018 Dec 17. doi: 10.1056/NEJMc1814130) – with a warning. “These results indicate that the policies in place as of the 2017-2018 school year were not sufficient to stop the spread of nicotine vaping among adolescents,” wrote the authors, led by Dr. Miech. “The rapid entry of new vaping devices on the market ... will require continual updates and modification strategies to keep adolescents from vaping and its associated negative health effects.”

The Monitoring the Future survey tracks annual drug use and drug use attitudes in a nationally representative sample of U.S. students in 8th, 10th, and 12th grades. This year’s survey included 44,482 participants. The survey is funded by a government grant to the University of Michigan, Ann Arbor, from the NIH’s NIDA.

Teenage use of vaping devices jumped significantly in the past year, with 37% of 12th-grade students reporting any vaping in 2018, compared with 28% in 2017, data announced Dec. 17 from the 2018 Monitoring the Future survey show.

LiudmylaSupynska/Thinkstock

In particular, nicotine vaping use in the 30 days prior to the survey nearly doubled among high school seniors, from approximately 11% in 2017 to 21% in 2018. Nicotine vaping also increased by 7.9% (from 8.2% to 16.1%) among 10th graders and by 2.6% (from 3.5% to 6.1%) among 8th graders, according to the survey results.

Vaping involves using a device such as an e-cigarette to inhale a heated aerosol product that usually contains nicotine but can be used to administer other types of drugs, said Nora D. Volkow, MD, director of the National Institute on Drug Abuse at the National Institutes of Health, in a press conference announcing the findings.

The increased prevalence of nicotine vaping in 10th and 12th graders is the largest annual increase in use of any substance recorded by Monitoring the Future, said Richard A. Miech, PhD, MPH, of the Institute for Social Research at the University of Michigan, Ann Arbor, and the principal survey investigator. “Something about this delivery device of vaping seems to really appeal to kids,” he said. The flavorings, concealability of the devices (which can be about the size of a flash drive), and ease of use seem to be contributing to the popularity of vaping, Dr. Miech added.

In addition, marijuana vaping increased significantly across all three grade levels in 2018 from 2017. Within 30 days of the survey, marijuana vaping increased from 4.9% to 7.5% in 12th graders, from 4.3% to 7.0% in 10th graders, and from 1.6% to 2.6% in 8th graders.

A take-home message for clinicians is the need to emphasize to teens that “vaping is not innocuous and not harmless,” said Dr. Miech in a question-and-answer session. Of note, data from multiple studies show that children who vape are about five times more likely to smoke cigarettes, he said.

The vaping devices are manufactured to deliver drugs into the lungs and ultimately high concentrations into the brain – which suggests the use of vaping devices to deliver other types of drugs might increase in the future, Dr. Volkow added.

Use of most other substances, including inhalants, heroin, cocaine, ecstasy, overall marijuana use, alcohol use, and extreme binge drinking remained stable, the researchers said. Cigarette smoking declined slightly among 12th graders but did not change significantly among 8th or 10th graders. Use of prescription opioids and tranquilizers declined in 2018 across all age groups.

“Vaping is reversing hard-fought declines in the number of adolescents who use nicotine,” Dr. Miech said in the news release announcing the results. “These results suggest that vaping is leading youth into nicotine use and nicotine addiction, not away from it.”

The data on vaping and nicotine use among American teens were published in a letter (N Engl J Med. 2018 Dec 17. doi: 10.1056/NEJMc1814130) – with a warning. “These results indicate that the policies in place as of the 2017-2018 school year were not sufficient to stop the spread of nicotine vaping among adolescents,” wrote the authors, led by Dr. Miech. “The rapid entry of new vaping devices on the market ... will require continual updates and modification strategies to keep adolescents from vaping and its associated negative health effects.”

The Monitoring the Future survey tracks annual drug use and drug use attitudes in a nationally representative sample of U.S. students in 8th, 10th, and 12th grades. This year’s survey included 44,482 participants. The survey is funded by a government grant to the University of Michigan, Ann Arbor, from the NIH’s NIDA.

Teenage use of vaping devices jumped significantly in the past year, with 37% of 12th-grade students reporting any vaping in 2018, compared with 28% in 2017, data announced Dec. 17 from the 2018 Monitoring the Future survey show.

LiudmylaSupynska/Thinkstock

In particular, nicotine vaping use in the 30 days prior to the survey nearly doubled among high school seniors, from approximately 11% in 2017 to 21% in 2018. Nicotine vaping also increased by 7.9% (from 8.2% to 16.1%) among 10th graders and by 2.6% (from 3.5% to 6.1%) among 8th graders, according to the survey results.

Vaping involves using a device such as an e-cigarette to inhale a heated aerosol product that usually contains nicotine but can be used to administer other types of drugs, said Nora D. Volkow, MD, director of the National Institute on Drug Abuse at the National Institutes of Health, in a press conference announcing the findings.

The increased prevalence of nicotine vaping in 10th and 12th graders is the largest annual increase in use of any substance recorded by Monitoring the Future, said Richard A. Miech, PhD, MPH, of the Institute for Social Research at the University of Michigan, Ann Arbor, and the principal survey investigator. “Something about this delivery device of vaping seems to really appeal to kids,” he said. The flavorings, concealability of the devices (which can be about the size of a flash drive), and ease of use seem to be contributing to the popularity of vaping, Dr. Miech added.

In addition, marijuana vaping increased significantly across all three grade levels in 2018 from 2017. Within 30 days of the survey, marijuana vaping increased from 4.9% to 7.5% in 12th graders, from 4.3% to 7.0% in 10th graders, and from 1.6% to 2.6% in 8th graders.

A take-home message for clinicians is the need to emphasize to teens that “vaping is not innocuous and not harmless,” said Dr. Miech in a question-and-answer session. Of note, data from multiple studies show that children who vape are about five times more likely to smoke cigarettes, he said.

The vaping devices are manufactured to deliver drugs into the lungs and ultimately high concentrations into the brain – which suggests the use of vaping devices to deliver other types of drugs might increase in the future, Dr. Volkow added.

Use of most other substances, including inhalants, heroin, cocaine, ecstasy, overall marijuana use, alcohol use, and extreme binge drinking remained stable, the researchers said. Cigarette smoking declined slightly among 12th graders but did not change significantly among 8th or 10th graders. Use of prescription opioids and tranquilizers declined in 2018 across all age groups.

“Vaping is reversing hard-fought declines in the number of adolescents who use nicotine,” Dr. Miech said in the news release announcing the results. “These results suggest that vaping is leading youth into nicotine use and nicotine addiction, not away from it.”

The data on vaping and nicotine use among American teens were published in a letter (N Engl J Med. 2018 Dec 17. doi: 10.1056/NEJMc1814130) – with a warning. “These results indicate that the policies in place as of the 2017-2018 school year were not sufficient to stop the spread of nicotine vaping among adolescents,” wrote the authors, led by Dr. Miech. “The rapid entry of new vaping devices on the market ... will require continual updates and modification strategies to keep adolescents from vaping and its associated negative health effects.”

The Monitoring the Future survey tracks annual drug use and drug use attitudes in a nationally representative sample of U.S. students in 8th, 10th, and 12th grades. This year’s survey included 44,482 participants. The survey is funded by a government grant to the University of Michigan, Ann Arbor, from the NIH’s NIDA.