The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

[email protected]

The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

[email protected]

The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

[email protected]

MILAN – Janus kinase (JAK) inhibitors have clear science supporting their use in alopecia areata, and an increasing number of positive studies demonstrate their efficacy in regrowing hair, Brett King, MD, PhD, said at the World Congress of Dermatology.

Although not yet specifically approved for alopecia areata, JAK inhibitors are already making their way into expert authored treatment algorithms for the management of this disease, said Dr. King, associate professor of dermatology at Yale University, New Haven, Conn.

“JAK inhibitors are very much within our reach for the treatment of severe alopecia areata,” Dr. King said in an oral presentation on therapeutic advances for alopecia. “We need to follow the science,” he added. “We would not be here telling a story about JAK inhibitors and these other agents without very bright scientists, so we really have to applaud the people who made this the focus of their research.”
 

JAK science

The science supporting JAK inhibitors can be traced back to a 2014 report by Angela M. Christiano, PhD,, Raphael Clynes, of Columbia University, New York, and others showing that alopecia areata is driven by cytotoxic T lymphocytes, and is reversed by inhibition of the JAK/STAT pathway in mouse models of disease (Nat Med. 2014 Sep;20[9]:1043-9). Those investigators also reported near-complete regrowth of hair in three patients who received oral ruxolitinib, an inhibitor of JAK1 and JAK2, hinting at the potential clinical importance of this targeted approach.

As Dr. King explained, secretion of interleukin (IL)-15 from the hair follicle endothelial cell activates CD8+NKG2D+ T cells leading to secretion of interferon (IFN)-gamma, which has a receptor on the hair follicle epithelial cell, activating that cell to secrete more IL-15.

“IL-15 and IFN-gamma both signal through the JAK/STAT pathway,” he said. “There are over 50 cytokines that signal through the JAK/STAT pathway, including IFN-gamma and IL-15, and on binding their receptor at the cell surface, they pass the baton, if you will, to the JAK enzymes, of which there are 4 members – JAK1, 2, 3 and tyrosine kinase 2. These enzymes subsequently pass the baton to STAT, and STAT translocates to the nucleus, where transcription occurs and disease happens. So we have an opportunity then with a small molecule JAK inhibitor to mediate disease, such that if we give this person a JAK inhibitor, they should regrow hair.”

JAK data

A number of studies of JAK inhibitors support that science, including an open-label study of 66 patients treated with the JAK1/3 inhibitor tofacitinib twice daily (JCI Insight. 2016 Sep 22;1[15]:e89776). About one-third experienced a 50% or greater improvement from baseline, as measured by the severity of alopecia tool (SALT) score over 3 months of treatment, with adverse events limited to grade 1-2 infections, according to the authors, which included Dr. King.

Around the same time, results of an open-label study with ruxolitinib, a JAK1/2 inhibitor, were published showing that 9 of 12 patients had complete or near complete scalp hair regrowth over 6 months of treatment, he said.

In a subsequent retrospective study of 90 patients treated with tofacitinib, about 66%-70% of patients experienced regrowth of hair, depending on the dose received. However, that study also showed that hair regrowth was unlikely in patients with complete or near complete scalp hair loss for 10 years or more, Dr. King said. An additional study showed that tofacitinib may be effective in adolescents as in adults, or even more effective, he added, while another found that low-dose ruxolitinib was as effective as higher dose ruxolitinib for the treatment of severe alopecia areata.

News earlier in 2019 surrounded the results of two randomized, double-blind placebo controlled trials, reported at the annual American Academy of Dermatology meeting in Washington, DC, showing efficacy for investigational oral JAK-targeted agents, a JAK 1/2 inhibitor (CTP-543), and a TYK2/JAK1 inhibitor (PF-06700841) and a JAK3 inhibitor (PF-06651600).

“I think this really is the near future of alopecia areata treatment,” Dr. King said.

No success yet for topical JAKs

One area where JAK inhibitors have not shined yet is in topical formulations. In a pilot study of tofacitinib 2% ointment, only 1 of 10 patients had significant scalp hair growth, while a study of topical ruxolitinib was stopped early and results have not yet been reported, according to Dr. King. “As dermatologists, we’re always interested in topical therapy for skin disease, but I’m not sure that alopecia areata is a disease for which topical JAK inhibitors will be effective,” he said.

Dr. King reported disclosures related to Aclaris Therapeutics, Concert Pharmaceuticals, Dermavant Sciences, Eli Lilly, Pfizer, Regeneron, and Sanofi Genzyme.

MILAN – Janus kinase (JAK) inhibitors have clear science supporting their use in alopecia areata, and an increasing number of positive studies demonstrate their efficacy in regrowing hair, Brett King, MD, PhD, said at the World Congress of Dermatology.

Although not yet specifically approved for alopecia areata, JAK inhibitors are already making their way into expert authored treatment algorithms for the management of this disease, said Dr. King, associate professor of dermatology at Yale University, New Haven, Conn.

“JAK inhibitors are very much within our reach for the treatment of severe alopecia areata,” Dr. King said in an oral presentation on therapeutic advances for alopecia. “We need to follow the science,” he added. “We would not be here telling a story about JAK inhibitors and these other agents without very bright scientists, so we really have to applaud the people who made this the focus of their research.”
 

JAK science

The science supporting JAK inhibitors can be traced back to a 2014 report by Angela M. Christiano, PhD,, Raphael Clynes, of Columbia University, New York, and others showing that alopecia areata is driven by cytotoxic T lymphocytes, and is reversed by inhibition of the JAK/STAT pathway in mouse models of disease (Nat Med. 2014 Sep;20[9]:1043-9). Those investigators also reported near-complete regrowth of hair in three patients who received oral ruxolitinib, an inhibitor of JAK1 and JAK2, hinting at the potential clinical importance of this targeted approach.

As Dr. King explained, secretion of interleukin (IL)-15 from the hair follicle endothelial cell activates CD8+NKG2D+ T cells leading to secretion of interferon (IFN)-gamma, which has a receptor on the hair follicle epithelial cell, activating that cell to secrete more IL-15.

“IL-15 and IFN-gamma both signal through the JAK/STAT pathway,” he said. “There are over 50 cytokines that signal through the JAK/STAT pathway, including IFN-gamma and IL-15, and on binding their receptor at the cell surface, they pass the baton, if you will, to the JAK enzymes, of which there are 4 members – JAK1, 2, 3 and tyrosine kinase 2. These enzymes subsequently pass the baton to STAT, and STAT translocates to the nucleus, where transcription occurs and disease happens. So we have an opportunity then with a small molecule JAK inhibitor to mediate disease, such that if we give this person a JAK inhibitor, they should regrow hair.”

JAK data

A number of studies of JAK inhibitors support that science, including an open-label study of 66 patients treated with the JAK1/3 inhibitor tofacitinib twice daily (JCI Insight. 2016 Sep 22;1[15]:e89776). About one-third experienced a 50% or greater improvement from baseline, as measured by the severity of alopecia tool (SALT) score over 3 months of treatment, with adverse events limited to grade 1-2 infections, according to the authors, which included Dr. King.

Around the same time, results of an open-label study with ruxolitinib, a JAK1/2 inhibitor, were published showing that 9 of 12 patients had complete or near complete scalp hair regrowth over 6 months of treatment, he said.

In a subsequent retrospective study of 90 patients treated with tofacitinib, about 66%-70% of patients experienced regrowth of hair, depending on the dose received. However, that study also showed that hair regrowth was unlikely in patients with complete or near complete scalp hair loss for 10 years or more, Dr. King said. An additional study showed that tofacitinib may be effective in adolescents as in adults, or even more effective, he added, while another found that low-dose ruxolitinib was as effective as higher dose ruxolitinib for the treatment of severe alopecia areata.

News earlier in 2019 surrounded the results of two randomized, double-blind placebo controlled trials, reported at the annual American Academy of Dermatology meeting in Washington, DC, showing efficacy for investigational oral JAK-targeted agents, a JAK 1/2 inhibitor (CTP-543), and a TYK2/JAK1 inhibitor (PF-06700841) and a JAK3 inhibitor (PF-06651600).

“I think this really is the near future of alopecia areata treatment,” Dr. King said.

No success yet for topical JAKs

One area where JAK inhibitors have not shined yet is in topical formulations. In a pilot study of tofacitinib 2% ointment, only 1 of 10 patients had significant scalp hair growth, while a study of topical ruxolitinib was stopped early and results have not yet been reported, according to Dr. King. “As dermatologists, we’re always interested in topical therapy for skin disease, but I’m not sure that alopecia areata is a disease for which topical JAK inhibitors will be effective,” he said.

Dr. King reported disclosures related to Aclaris Therapeutics, Concert Pharmaceuticals, Dermavant Sciences, Eli Lilly, Pfizer, Regeneron, and Sanofi Genzyme.

MILAN – Janus kinase (JAK) inhibitors have clear science supporting their use in alopecia areata, and an increasing number of positive studies demonstrate their efficacy in regrowing hair, Brett King, MD, PhD, said at the World Congress of Dermatology.

Although not yet specifically approved for alopecia areata, JAK inhibitors are already making their way into expert authored treatment algorithms for the management of this disease, said Dr. King, associate professor of dermatology at Yale University, New Haven, Conn.

“JAK inhibitors are very much within our reach for the treatment of severe alopecia areata,” Dr. King said in an oral presentation on therapeutic advances for alopecia. “We need to follow the science,” he added. “We would not be here telling a story about JAK inhibitors and these other agents without very bright scientists, so we really have to applaud the people who made this the focus of their research.”
 

JAK science

The science supporting JAK inhibitors can be traced back to a 2014 report by Angela M. Christiano, PhD,, Raphael Clynes, of Columbia University, New York, and others showing that alopecia areata is driven by cytotoxic T lymphocytes, and is reversed by inhibition of the JAK/STAT pathway in mouse models of disease (Nat Med. 2014 Sep;20[9]:1043-9). Those investigators also reported near-complete regrowth of hair in three patients who received oral ruxolitinib, an inhibitor of JAK1 and JAK2, hinting at the potential clinical importance of this targeted approach.

As Dr. King explained, secretion of interleukin (IL)-15 from the hair follicle endothelial cell activates CD8+NKG2D+ T cells leading to secretion of interferon (IFN)-gamma, which has a receptor on the hair follicle epithelial cell, activating that cell to secrete more IL-15.

“IL-15 and IFN-gamma both signal through the JAK/STAT pathway,” he said. “There are over 50 cytokines that signal through the JAK/STAT pathway, including IFN-gamma and IL-15, and on binding their receptor at the cell surface, they pass the baton, if you will, to the JAK enzymes, of which there are 4 members – JAK1, 2, 3 and tyrosine kinase 2. These enzymes subsequently pass the baton to STAT, and STAT translocates to the nucleus, where transcription occurs and disease happens. So we have an opportunity then with a small molecule JAK inhibitor to mediate disease, such that if we give this person a JAK inhibitor, they should regrow hair.”

JAK data

A number of studies of JAK inhibitors support that science, including an open-label study of 66 patients treated with the JAK1/3 inhibitor tofacitinib twice daily (JCI Insight. 2016 Sep 22;1[15]:e89776). About one-third experienced a 50% or greater improvement from baseline, as measured by the severity of alopecia tool (SALT) score over 3 months of treatment, with adverse events limited to grade 1-2 infections, according to the authors, which included Dr. King.

Around the same time, results of an open-label study with ruxolitinib, a JAK1/2 inhibitor, were published showing that 9 of 12 patients had complete or near complete scalp hair regrowth over 6 months of treatment, he said.

In a subsequent retrospective study of 90 patients treated with tofacitinib, about 66%-70% of patients experienced regrowth of hair, depending on the dose received. However, that study also showed that hair regrowth was unlikely in patients with complete or near complete scalp hair loss for 10 years or more, Dr. King said. An additional study showed that tofacitinib may be effective in adolescents as in adults, or even more effective, he added, while another found that low-dose ruxolitinib was as effective as higher dose ruxolitinib for the treatment of severe alopecia areata.

News earlier in 2019 surrounded the results of two randomized, double-blind placebo controlled trials, reported at the annual American Academy of Dermatology meeting in Washington, DC, showing efficacy for investigational oral JAK-targeted agents, a JAK 1/2 inhibitor (CTP-543), and a TYK2/JAK1 inhibitor (PF-06700841) and a JAK3 inhibitor (PF-06651600).

“I think this really is the near future of alopecia areata treatment,” Dr. King said.

No success yet for topical JAKs

One area where JAK inhibitors have not shined yet is in topical formulations. In a pilot study of tofacitinib 2% ointment, only 1 of 10 patients had significant scalp hair growth, while a study of topical ruxolitinib was stopped early and results have not yet been reported, according to Dr. King. “As dermatologists, we’re always interested in topical therapy for skin disease, but I’m not sure that alopecia areata is a disease for which topical JAK inhibitors will be effective,” he said.

Dr. King reported disclosures related to Aclaris Therapeutics, Concert Pharmaceuticals, Dermavant Sciences, Eli Lilly, Pfizer, Regeneron, and Sanofi Genzyme.

NASHVILLE, TENN. – The use of long-acting reversible contraceptive (LARC) methods reduces short interpregnancy intervals, but does not appear to reduce the risk of preterm birth when used between a first and second pregnancy, results of a retrospective cohort study suggest.

Sharon Worcester/MDedge News

Of 35,754 women who had a first and second live birth between 2005 and 2015 and who received non-emergent care within 10 years of the first birth, 3,083 (9%) had evidence of interpregnancy LARC exposure and were significantly less likely to have short interpregnancy intervals than were 32,671 with either non-LARC contraceptive use or no record of contraceptive-related care (P less than .0001), Sara E. Simonsen, PhD, reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.

Intervals in those with intrapartum LARC use were 12 months or less in 4% of women, 13-18 months in 8%, 19-24 months in 11%, and greater than 24 months in 13%.

However, preterm birth, which occurred in 7% of first births and 6% of second births, was not lower among those with LARC exposure vs. those with no contraceptive encounters after adjustment for interpregnancy interval and a number of demographic factors, including education, presence of father, mother’s age, Hispanic ethnicity, fetal anomalies, and preterm birth history (adjusted odds ratio, 1.13), said Dr. Simonsen, a certified nurse midwife at the University of Utah Hospital, Salt Lake City.

“Preterm birth, a live birth at less than 37 weeks’ gestation, is a major determinant of poor neonatal outcomes,” she and her colleagues wrote. “Short interpregnancy interval, defined as less than 18 months, is an important risk factor for preterm birth.”

Given the increasing number of U.S. women who use highly effective LARCs to space pregnancies, she and her colleagues performed a retrospective cohort study of electronic medical records from two large health systems and linked them with birth and fetal death records to explore the relationship between interpregnancy LARC and both interpregnancy interval and preterm birth in the subsequent pregnancy.

“We did find that women who used LARC between their pregnancies were less likely to have a short interpregnancy interval, but in adjusted models ... we found no association with intrapartum LARC use and preterm birth in the second birth,” Dr. Simonsen said during an e-poster presentation at the meeting.

In fact, preterm birth in the second birth was most strongly associated with a prior preterm birth – a finding consistent with the literature, she and her colleagues noted.

Although the findings are limited by the use of retrospective data not designed for research, the data came from a large population-based sample representing about 85% of Utah births, they said.

The findings suggest that while LARC use may not reduce preterm birth risk, it “may contribute favorably to outcomes to the extent that having optimal interpregnancy interval does,” they wrote.

“‘We feel that these findings support providers counseling women on the full range of contraception options in the postpartum and not pushing [intrauterine devices,]” Dr. Simonsen added.

The related topic of immediate postpartum LARC use was addressed by Eve Espey, MD, in a separate presentation at the meeting.

Dr .Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque, reported that immediate postpartum insertion of an intrauterine device (IUD) is highly cost-effective despite an expulsion rate of between 10% and 30%. She also addressed the value of postpartum LARC for reducing rapid-repeat pregnancy rates.

Payment models for immediate postpartum LARC are “very cumbersome,” but at the university, a persistent effort over 4 years has led to success. Immediate postpartum LARC is offered to women with Medicaid coverage, and payment is received in about 97% of cases, she said, adding that efforts are underway to help other hospitals “troubleshoot the issues.”

The lack of private insurance coverage for immediate postpartum LARC remains a challenge, but Dr. Espey said she remains “super enthusiastic” about its use.

“I think it’s going to take another 5 years or so [for better coverage], and honestly I think what we really need is an inpatient LARC CPT code to make this happen,” she said, urging colleagues to advocate for that within their American College of Obstetricians and Gynecologists sections when possible.

Dr. Simonsen and Dr. Espey reported having no relevant disclosures.

[email protected]

NASHVILLE, TENN. – The use of long-acting reversible contraceptive (LARC) methods reduces short interpregnancy intervals, but does not appear to reduce the risk of preterm birth when used between a first and second pregnancy, results of a retrospective cohort study suggest.

Sharon Worcester/MDedge News

Of 35,754 women who had a first and second live birth between 2005 and 2015 and who received non-emergent care within 10 years of the first birth, 3,083 (9%) had evidence of interpregnancy LARC exposure and were significantly less likely to have short interpregnancy intervals than were 32,671 with either non-LARC contraceptive use or no record of contraceptive-related care (P less than .0001), Sara E. Simonsen, PhD, reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.

Intervals in those with intrapartum LARC use were 12 months or less in 4% of women, 13-18 months in 8%, 19-24 months in 11%, and greater than 24 months in 13%.

However, preterm birth, which occurred in 7% of first births and 6% of second births, was not lower among those with LARC exposure vs. those with no contraceptive encounters after adjustment for interpregnancy interval and a number of demographic factors, including education, presence of father, mother’s age, Hispanic ethnicity, fetal anomalies, and preterm birth history (adjusted odds ratio, 1.13), said Dr. Simonsen, a certified nurse midwife at the University of Utah Hospital, Salt Lake City.

“Preterm birth, a live birth at less than 37 weeks’ gestation, is a major determinant of poor neonatal outcomes,” she and her colleagues wrote. “Short interpregnancy interval, defined as less than 18 months, is an important risk factor for preterm birth.”

Given the increasing number of U.S. women who use highly effective LARCs to space pregnancies, she and her colleagues performed a retrospective cohort study of electronic medical records from two large health systems and linked them with birth and fetal death records to explore the relationship between interpregnancy LARC and both interpregnancy interval and preterm birth in the subsequent pregnancy.

“We did find that women who used LARC between their pregnancies were less likely to have a short interpregnancy interval, but in adjusted models ... we found no association with intrapartum LARC use and preterm birth in the second birth,” Dr. Simonsen said during an e-poster presentation at the meeting.

In fact, preterm birth in the second birth was most strongly associated with a prior preterm birth – a finding consistent with the literature, she and her colleagues noted.

Although the findings are limited by the use of retrospective data not designed for research, the data came from a large population-based sample representing about 85% of Utah births, they said.

The findings suggest that while LARC use may not reduce preterm birth risk, it “may contribute favorably to outcomes to the extent that having optimal interpregnancy interval does,” they wrote.

“‘We feel that these findings support providers counseling women on the full range of contraception options in the postpartum and not pushing [intrauterine devices,]” Dr. Simonsen added.

The related topic of immediate postpartum LARC use was addressed by Eve Espey, MD, in a separate presentation at the meeting.

Dr .Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque, reported that immediate postpartum insertion of an intrauterine device (IUD) is highly cost-effective despite an expulsion rate of between 10% and 30%. She also addressed the value of postpartum LARC for reducing rapid-repeat pregnancy rates.

Payment models for immediate postpartum LARC are “very cumbersome,” but at the university, a persistent effort over 4 years has led to success. Immediate postpartum LARC is offered to women with Medicaid coverage, and payment is received in about 97% of cases, she said, adding that efforts are underway to help other hospitals “troubleshoot the issues.”

The lack of private insurance coverage for immediate postpartum LARC remains a challenge, but Dr. Espey said she remains “super enthusiastic” about its use.

“I think it’s going to take another 5 years or so [for better coverage], and honestly I think what we really need is an inpatient LARC CPT code to make this happen,” she said, urging colleagues to advocate for that within their American College of Obstetricians and Gynecologists sections when possible.

Dr. Simonsen and Dr. Espey reported having no relevant disclosures.

[email protected]

NASHVILLE, TENN. – The use of long-acting reversible contraceptive (LARC) methods reduces short interpregnancy intervals, but does not appear to reduce the risk of preterm birth when used between a first and second pregnancy, results of a retrospective cohort study suggest.

Sharon Worcester/MDedge News

Of 35,754 women who had a first and second live birth between 2005 and 2015 and who received non-emergent care within 10 years of the first birth, 3,083 (9%) had evidence of interpregnancy LARC exposure and were significantly less likely to have short interpregnancy intervals than were 32,671 with either non-LARC contraceptive use or no record of contraceptive-related care (P less than .0001), Sara E. Simonsen, PhD, reported in a poster at the annual meeting of the American College of Obstetricians and Gynecologists.

Intervals in those with intrapartum LARC use were 12 months or less in 4% of women, 13-18 months in 8%, 19-24 months in 11%, and greater than 24 months in 13%.

However, preterm birth, which occurred in 7% of first births and 6% of second births, was not lower among those with LARC exposure vs. those with no contraceptive encounters after adjustment for interpregnancy interval and a number of demographic factors, including education, presence of father, mother’s age, Hispanic ethnicity, fetal anomalies, and preterm birth history (adjusted odds ratio, 1.13), said Dr. Simonsen, a certified nurse midwife at the University of Utah Hospital, Salt Lake City.

“Preterm birth, a live birth at less than 37 weeks’ gestation, is a major determinant of poor neonatal outcomes,” she and her colleagues wrote. “Short interpregnancy interval, defined as less than 18 months, is an important risk factor for preterm birth.”

Given the increasing number of U.S. women who use highly effective LARCs to space pregnancies, she and her colleagues performed a retrospective cohort study of electronic medical records from two large health systems and linked them with birth and fetal death records to explore the relationship between interpregnancy LARC and both interpregnancy interval and preterm birth in the subsequent pregnancy.

“We did find that women who used LARC between their pregnancies were less likely to have a short interpregnancy interval, but in adjusted models ... we found no association with intrapartum LARC use and preterm birth in the second birth,” Dr. Simonsen said during an e-poster presentation at the meeting.

In fact, preterm birth in the second birth was most strongly associated with a prior preterm birth – a finding consistent with the literature, she and her colleagues noted.

Although the findings are limited by the use of retrospective data not designed for research, the data came from a large population-based sample representing about 85% of Utah births, they said.

The findings suggest that while LARC use may not reduce preterm birth risk, it “may contribute favorably to outcomes to the extent that having optimal interpregnancy interval does,” they wrote.

“‘We feel that these findings support providers counseling women on the full range of contraception options in the postpartum and not pushing [intrauterine devices,]” Dr. Simonsen added.

The related topic of immediate postpartum LARC use was addressed by Eve Espey, MD, in a separate presentation at the meeting.

Dr .Espey, professor and chair of the department of obstetrics and gynecology and director of the family planning fellowship at the University of New Mexico, Albuquerque, reported that immediate postpartum insertion of an intrauterine device (IUD) is highly cost-effective despite an expulsion rate of between 10% and 30%. She also addressed the value of postpartum LARC for reducing rapid-repeat pregnancy rates.

Payment models for immediate postpartum LARC are “very cumbersome,” but at the university, a persistent effort over 4 years has led to success. Immediate postpartum LARC is offered to women with Medicaid coverage, and payment is received in about 97% of cases, she said, adding that efforts are underway to help other hospitals “troubleshoot the issues.”

The lack of private insurance coverage for immediate postpartum LARC remains a challenge, but Dr. Espey said she remains “super enthusiastic” about its use.

“I think it’s going to take another 5 years or so [for better coverage], and honestly I think what we really need is an inpatient LARC CPT code to make this happen,” she said, urging colleagues to advocate for that within their American College of Obstetricians and Gynecologists sections when possible.

Dr. Simonsen and Dr. Espey reported having no relevant disclosures.

[email protected]

Adding an immune modulator (IM) to anti–tumor necrosis factor (anti-TNF) initiation therapy benefits patients with Crohn’s disease (CD) but not those with ulcerative colitis (UC), according to a recent retrospective look at more than 1,000 cases.

The study showed that patients with CD who started combination therapy instead of monotherapy had lower rates of treatment ineffectiveness, experienced longer delays until hospitalization, and less often needed to switch their anti-TNF agent, reported lead author Laura E. Targownik, MD, of the University of Manitoba, in Winnipeg, Canada, and colleagues.

“Current guidelines on the medical management of IBD strongly support the use of IMs and anti-TNFs in combination over anti-TNF monotherapy,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, there is a sparsity of real-world data demonstrating the incremental benefits of combination therapy.”

The investigators noted that the SONIC trial, conducted in 2010, showed that patients treated with combination therapy were more likely to achieve corticosteroid-free remission at weeks 26 and 50; this became the basis of evidence leading multiple clinical guidelines to recommend combination therapy for patients with CD.

The present study involved 852 patients with CD and 303 with UC who began treatment with an anti-TNF agent during 2001-2016. Data were drawn from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database.

The main outcome of interest was treatment ineffectiveness, which was defined by any of the following four events: acute, IBD-related hospital admission for more than 48 hours; resective intestinal surgery; corticosteroid use at least 14 days after initiating anti-TNF therapy, or, if corticosteroids were used within 16 weeks of anti-TNF initiation, then subsequent corticosteroid use occurring at least 16 weeks after initiation; or switching to a different anti-TNF agent. The investigators also looked for differences in effectiveness between two agents from each class: anti-TNF agents infliximab and adalimumab, and immunomodulators methotrexate and azathioprine.

Results showed that patients with CD had higher rates of ineffectiveness-free survival when treated with combination therapy instead of monotherapy at 1 year (74.2% vs. 68.6%) and 2 years (64.0% vs. 54.5%). Using a Cox proportional hazards model, this translated to a 38% reduced risk of treatment ineffectiveness (adjusted hazard ratio, 0.62).

“This suggests that the findings of the SONIC trial may extend to real-world clinical practice, even in patients who had previous IM exposure,” the investigators noted.

Combination therapy was also significantly associated with longer time to first IBD-related hospitalization (HR, 0.53) and the need to switch anti-TNF agent (HR, 0.63). However, no such relationships were found for time to resective surgery or corticosteroid use. Although combination therapy had no impact on the rate of primary treatment ineffectiveness in multivariable logistic regression, those who received anti-TNF therapy for more than 90 days had delayed secondary treatment ineffectiveness and fewer IBD-related hospitalizations. Choice of agent from either class had no influence on effectiveness of combination therapy.

In contrast with the above findings, combination therapy in patients with UC was less promising, which aligns with previous studies.

“[W]e were not able to demonstrate a significant advantage to combination therapy in persons with UC,” the investigators wrote. “In addition, all published cohort studies to date have not been able to confirm a significant benefit to combination therapy in UC. ... In light of the lower quality of prior evidence, combined with the results from our study, the indication for combination therapy in UC would appear to be weaker.”

“Further analyses in larger cohorts may clarify whether there is a clinically relevant benefit of combination therapy in persons with UC,” the investigators concluded. “Because of the discrepancy between our findings and those of a meta-analysis of cohort studies previously published on this topic, confirmation of our results is required in future studies.”

The investigators disclosed no funding or conflicts of interest.

SOURCE: Targownik LE et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.003.

Adding an immune modulator (IM) to anti–tumor necrosis factor (anti-TNF) initiation therapy benefits patients with Crohn’s disease (CD) but not those with ulcerative colitis (UC), according to a recent retrospective look at more than 1,000 cases.

The study showed that patients with CD who started combination therapy instead of monotherapy had lower rates of treatment ineffectiveness, experienced longer delays until hospitalization, and less often needed to switch their anti-TNF agent, reported lead author Laura E. Targownik, MD, of the University of Manitoba, in Winnipeg, Canada, and colleagues.

“Current guidelines on the medical management of IBD strongly support the use of IMs and anti-TNFs in combination over anti-TNF monotherapy,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, there is a sparsity of real-world data demonstrating the incremental benefits of combination therapy.”

The investigators noted that the SONIC trial, conducted in 2010, showed that patients treated with combination therapy were more likely to achieve corticosteroid-free remission at weeks 26 and 50; this became the basis of evidence leading multiple clinical guidelines to recommend combination therapy for patients with CD.

The present study involved 852 patients with CD and 303 with UC who began treatment with an anti-TNF agent during 2001-2016. Data were drawn from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database.

The main outcome of interest was treatment ineffectiveness, which was defined by any of the following four events: acute, IBD-related hospital admission for more than 48 hours; resective intestinal surgery; corticosteroid use at least 14 days after initiating anti-TNF therapy, or, if corticosteroids were used within 16 weeks of anti-TNF initiation, then subsequent corticosteroid use occurring at least 16 weeks after initiation; or switching to a different anti-TNF agent. The investigators also looked for differences in effectiveness between two agents from each class: anti-TNF agents infliximab and adalimumab, and immunomodulators methotrexate and azathioprine.

Results showed that patients with CD had higher rates of ineffectiveness-free survival when treated with combination therapy instead of monotherapy at 1 year (74.2% vs. 68.6%) and 2 years (64.0% vs. 54.5%). Using a Cox proportional hazards model, this translated to a 38% reduced risk of treatment ineffectiveness (adjusted hazard ratio, 0.62).

“This suggests that the findings of the SONIC trial may extend to real-world clinical practice, even in patients who had previous IM exposure,” the investigators noted.

Combination therapy was also significantly associated with longer time to first IBD-related hospitalization (HR, 0.53) and the need to switch anti-TNF agent (HR, 0.63). However, no such relationships were found for time to resective surgery or corticosteroid use. Although combination therapy had no impact on the rate of primary treatment ineffectiveness in multivariable logistic regression, those who received anti-TNF therapy for more than 90 days had delayed secondary treatment ineffectiveness and fewer IBD-related hospitalizations. Choice of agent from either class had no influence on effectiveness of combination therapy.

In contrast with the above findings, combination therapy in patients with UC was less promising, which aligns with previous studies.

“[W]e were not able to demonstrate a significant advantage to combination therapy in persons with UC,” the investigators wrote. “In addition, all published cohort studies to date have not been able to confirm a significant benefit to combination therapy in UC. ... In light of the lower quality of prior evidence, combined with the results from our study, the indication for combination therapy in UC would appear to be weaker.”

“Further analyses in larger cohorts may clarify whether there is a clinically relevant benefit of combination therapy in persons with UC,” the investigators concluded. “Because of the discrepancy between our findings and those of a meta-analysis of cohort studies previously published on this topic, confirmation of our results is required in future studies.”

The investigators disclosed no funding or conflicts of interest.

SOURCE: Targownik LE et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.003.

Adding an immune modulator (IM) to anti–tumor necrosis factor (anti-TNF) initiation therapy benefits patients with Crohn’s disease (CD) but not those with ulcerative colitis (UC), according to a recent retrospective look at more than 1,000 cases.

The study showed that patients with CD who started combination therapy instead of monotherapy had lower rates of treatment ineffectiveness, experienced longer delays until hospitalization, and less often needed to switch their anti-TNF agent, reported lead author Laura E. Targownik, MD, of the University of Manitoba, in Winnipeg, Canada, and colleagues.

“Current guidelines on the medical management of IBD strongly support the use of IMs and anti-TNFs in combination over anti-TNF monotherapy,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, there is a sparsity of real-world data demonstrating the incremental benefits of combination therapy.”

The investigators noted that the SONIC trial, conducted in 2010, showed that patients treated with combination therapy were more likely to achieve corticosteroid-free remission at weeks 26 and 50; this became the basis of evidence leading multiple clinical guidelines to recommend combination therapy for patients with CD.

The present study involved 852 patients with CD and 303 with UC who began treatment with an anti-TNF agent during 2001-2016. Data were drawn from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database.

The main outcome of interest was treatment ineffectiveness, which was defined by any of the following four events: acute, IBD-related hospital admission for more than 48 hours; resective intestinal surgery; corticosteroid use at least 14 days after initiating anti-TNF therapy, or, if corticosteroids were used within 16 weeks of anti-TNF initiation, then subsequent corticosteroid use occurring at least 16 weeks after initiation; or switching to a different anti-TNF agent. The investigators also looked for differences in effectiveness between two agents from each class: anti-TNF agents infliximab and adalimumab, and immunomodulators methotrexate and azathioprine.

Results showed that patients with CD had higher rates of ineffectiveness-free survival when treated with combination therapy instead of monotherapy at 1 year (74.2% vs. 68.6%) and 2 years (64.0% vs. 54.5%). Using a Cox proportional hazards model, this translated to a 38% reduced risk of treatment ineffectiveness (adjusted hazard ratio, 0.62).

“This suggests that the findings of the SONIC trial may extend to real-world clinical practice, even in patients who had previous IM exposure,” the investigators noted.

Combination therapy was also significantly associated with longer time to first IBD-related hospitalization (HR, 0.53) and the need to switch anti-TNF agent (HR, 0.63). However, no such relationships were found for time to resective surgery or corticosteroid use. Although combination therapy had no impact on the rate of primary treatment ineffectiveness in multivariable logistic regression, those who received anti-TNF therapy for more than 90 days had delayed secondary treatment ineffectiveness and fewer IBD-related hospitalizations. Choice of agent from either class had no influence on effectiveness of combination therapy.

In contrast with the above findings, combination therapy in patients with UC was less promising, which aligns with previous studies.

“[W]e were not able to demonstrate a significant advantage to combination therapy in persons with UC,” the investigators wrote. “In addition, all published cohort studies to date have not been able to confirm a significant benefit to combination therapy in UC. ... In light of the lower quality of prior evidence, combined with the results from our study, the indication for combination therapy in UC would appear to be weaker.”

“Further analyses in larger cohorts may clarify whether there is a clinically relevant benefit of combination therapy in persons with UC,” the investigators concluded. “Because of the discrepancy between our findings and those of a meta-analysis of cohort studies previously published on this topic, confirmation of our results is required in future studies.”

The investigators disclosed no funding or conflicts of interest.

SOURCE: Targownik LE et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.003.

MILAN – Biologics are underprescribed in the elderly, despite evidence that efficacy of biologics is comparable among older and younger patients over time, an analysis of German and Swiss registry data shows.

There was an “imbalance” in the types of medications prescribed for older and younger patients in the registry, with biologics used more frequently in younger patients, according to investigator Matthias Augustin, MD, director of the Institute For Health Services Research in Dermatology and Nursing in Hamburg, Germany.

However, the efficacy of systemic treatments, including nonbiologic therapies, was comparable between older and younger patients, other than a few differences in response rates early in treatment that disappeared with longer follow-up, Dr. Augustin said at the World Congress of Dermatology. Coupled with evidence from the medical literature, results of this registry data analysis suggest there are “very few reasons” to avoid use of systemic drugs in elderly patients.

“I think we should create awareness and discuss possible reasons that deter dermatologists from prescribing systemic antipsoriatics in elderly patients,” he said.

Concerns about safety and drug interactions in the elderly may be one barrier to prescribing systemic therapy in this patient population: More data on this issue are needed, since the elderly are taking more medications than younger patients and have more contraindications, Dr. Augustin said. “I think this is a job for all registries for the future.”

Older individuals have typically been excluded from psoriasis clinical trials, making it difficult to extrapolate existing safety and efficacy data to those patients, he pointed out.

Accordingly, Dr. Augustin and coinvestigators evaluated prospectively collected data for patients with moderate to severe psoriasis who were included in either the German Psoriasis registry (PsoBest) or the Swiss Dermatology Network for Targeted Therapies (SDNTT). They split the cohort into a control group of those younger than 65 years (about 4,600 individuals) and those 65 years or older (about 740 individuals).

A few systemic drugs were used more frequently in the elderly, including apremilast and methotrexate, while most other drugs, including biologics, were used more frequently in younger patients, Dr. Augustin and colleagues found in their analysis. There were a few differences between the elderly and controls related to weight, smoking, and other factors, but not so pronounced that they would explain differences in the use of the systemic therapy.

Response rates to systemic therapies were generally comparable between the elderly and controls, as measured by Psoriasis Area Severity Index (PASI) 75 responses, PASI scores of 3 or less, and Dermatology Life Quality Index scores of one or less, he added.

One exception was methotrexate, which was more effective in the elderly after 3 and 6 months of treatment, but that difference was no longer apparent after 12 months of treatment, he said. Likewise, cyclosporine showed a higher response rate in younger patients at 3 months, but not at 6 or 12 months.

Based on the findings, “overall, we observed comparable responses between the controls and the elderly,” Dr. Augustin concluded.

The PsoBest registry is sponsored by CVderm, DDG, and BVDD, and “has been established and is operated in close cooperation with the involved pharmaceutical companies whose statutory pharmacovigilance requirements are taken into account,” according to a statement on the PsoBest website. The Swiss registry is supported by Janssen, AbbVie, Pfizer, Celgene, Lilly, and Novartis. The investigators did not report any disclosures.

MILAN – Biologics are underprescribed in the elderly, despite evidence that efficacy of biologics is comparable among older and younger patients over time, an analysis of German and Swiss registry data shows.

There was an “imbalance” in the types of medications prescribed for older and younger patients in the registry, with biologics used more frequently in younger patients, according to investigator Matthias Augustin, MD, director of the Institute For Health Services Research in Dermatology and Nursing in Hamburg, Germany.

However, the efficacy of systemic treatments, including nonbiologic therapies, was comparable between older and younger patients, other than a few differences in response rates early in treatment that disappeared with longer follow-up, Dr. Augustin said at the World Congress of Dermatology. Coupled with evidence from the medical literature, results of this registry data analysis suggest there are “very few reasons” to avoid use of systemic drugs in elderly patients.

“I think we should create awareness and discuss possible reasons that deter dermatologists from prescribing systemic antipsoriatics in elderly patients,” he said.

Concerns about safety and drug interactions in the elderly may be one barrier to prescribing systemic therapy in this patient population: More data on this issue are needed, since the elderly are taking more medications than younger patients and have more contraindications, Dr. Augustin said. “I think this is a job for all registries for the future.”

Older individuals have typically been excluded from psoriasis clinical trials, making it difficult to extrapolate existing safety and efficacy data to those patients, he pointed out.

Accordingly, Dr. Augustin and coinvestigators evaluated prospectively collected data for patients with moderate to severe psoriasis who were included in either the German Psoriasis registry (PsoBest) or the Swiss Dermatology Network for Targeted Therapies (SDNTT). They split the cohort into a control group of those younger than 65 years (about 4,600 individuals) and those 65 years or older (about 740 individuals).

A few systemic drugs were used more frequently in the elderly, including apremilast and methotrexate, while most other drugs, including biologics, were used more frequently in younger patients, Dr. Augustin and colleagues found in their analysis. There were a few differences between the elderly and controls related to weight, smoking, and other factors, but not so pronounced that they would explain differences in the use of the systemic therapy.

Response rates to systemic therapies were generally comparable between the elderly and controls, as measured by Psoriasis Area Severity Index (PASI) 75 responses, PASI scores of 3 or less, and Dermatology Life Quality Index scores of one or less, he added.

One exception was methotrexate, which was more effective in the elderly after 3 and 6 months of treatment, but that difference was no longer apparent after 12 months of treatment, he said. Likewise, cyclosporine showed a higher response rate in younger patients at 3 months, but not at 6 or 12 months.

Based on the findings, “overall, we observed comparable responses between the controls and the elderly,” Dr. Augustin concluded.

The PsoBest registry is sponsored by CVderm, DDG, and BVDD, and “has been established and is operated in close cooperation with the involved pharmaceutical companies whose statutory pharmacovigilance requirements are taken into account,” according to a statement on the PsoBest website. The Swiss registry is supported by Janssen, AbbVie, Pfizer, Celgene, Lilly, and Novartis. The investigators did not report any disclosures.

MILAN – Biologics are underprescribed in the elderly, despite evidence that efficacy of biologics is comparable among older and younger patients over time, an analysis of German and Swiss registry data shows.

There was an “imbalance” in the types of medications prescribed for older and younger patients in the registry, with biologics used more frequently in younger patients, according to investigator Matthias Augustin, MD, director of the Institute For Health Services Research in Dermatology and Nursing in Hamburg, Germany.

However, the efficacy of systemic treatments, including nonbiologic therapies, was comparable between older and younger patients, other than a few differences in response rates early in treatment that disappeared with longer follow-up, Dr. Augustin said at the World Congress of Dermatology. Coupled with evidence from the medical literature, results of this registry data analysis suggest there are “very few reasons” to avoid use of systemic drugs in elderly patients.

“I think we should create awareness and discuss possible reasons that deter dermatologists from prescribing systemic antipsoriatics in elderly patients,” he said.

Concerns about safety and drug interactions in the elderly may be one barrier to prescribing systemic therapy in this patient population: More data on this issue are needed, since the elderly are taking more medications than younger patients and have more contraindications, Dr. Augustin said. “I think this is a job for all registries for the future.”

Older individuals have typically been excluded from psoriasis clinical trials, making it difficult to extrapolate existing safety and efficacy data to those patients, he pointed out.

Accordingly, Dr. Augustin and coinvestigators evaluated prospectively collected data for patients with moderate to severe psoriasis who were included in either the German Psoriasis registry (PsoBest) or the Swiss Dermatology Network for Targeted Therapies (SDNTT). They split the cohort into a control group of those younger than 65 years (about 4,600 individuals) and those 65 years or older (about 740 individuals).

A few systemic drugs were used more frequently in the elderly, including apremilast and methotrexate, while most other drugs, including biologics, were used more frequently in younger patients, Dr. Augustin and colleagues found in their analysis. There were a few differences between the elderly and controls related to weight, smoking, and other factors, but not so pronounced that they would explain differences in the use of the systemic therapy.

Response rates to systemic therapies were generally comparable between the elderly and controls, as measured by Psoriasis Area Severity Index (PASI) 75 responses, PASI scores of 3 or less, and Dermatology Life Quality Index scores of one or less, he added.

One exception was methotrexate, which was more effective in the elderly after 3 and 6 months of treatment, but that difference was no longer apparent after 12 months of treatment, he said. Likewise, cyclosporine showed a higher response rate in younger patients at 3 months, but not at 6 or 12 months.

Based on the findings, “overall, we observed comparable responses between the controls and the elderly,” Dr. Augustin concluded.

The PsoBest registry is sponsored by CVderm, DDG, and BVDD, and “has been established and is operated in close cooperation with the involved pharmaceutical companies whose statutory pharmacovigilance requirements are taken into account,” according to a statement on the PsoBest website. The Swiss registry is supported by Janssen, AbbVie, Pfizer, Celgene, Lilly, and Novartis. The investigators did not report any disclosures.

MILAN – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, according to a report presented at the World Congress of Dermatology.

Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).

These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.

“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”

Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.


In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.

Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).

In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.

The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).

Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.

That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”

Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.

The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.

Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.

Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.

MILAN – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, according to a report presented at the World Congress of Dermatology.

Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).

These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.

“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”

Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.


In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.

Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).

In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.

The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).

Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.

That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”

Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.

The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.

Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.

Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.

MILAN – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, according to a report presented at the World Congress of Dermatology.

Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).

These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.

“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”

Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.


In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.

Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).

In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.

The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).

Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.

That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”

Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.

The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.

Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.

Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.

NASHVILLE, TENN. – Many women with endometriosis experience dyspareunia, but they are largely unsatisfied when it comes to discussions with health care providers about their symptoms, the results of an online survey suggest.

Of 638 women with self-reported endometriosis who responded to the survey, 81% said they always or usually experience pain during intercourse, 51% described their pain as severe, and 49% said they experience pain lasting more than 24 hours, Roberta Renzelli-Cain, DO, reported during a poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“The results of our survey suggest that endometriosis-related pelvic pain and dyspareunia is a significant symptom, it is life changing, and it is frequently not addressed by health care providers,” said Dr. Renzelli-Cain, director of the West Virginia National Center of Excellence in Women’s Health and an ob.gyn. at West Virginia University, Morgantown.

In fact, survey responses suggested that dyspareunia has a marked impact on quality of life; 69% of respondents said they find sexual intercourse unpleasant, 31% said they always or usually avoid intercourse, 44% strongly agreed that dyspareunia has affected their relationship with their spouse or partner, 63% said they worry that their spouse or partner will leave, and 63% said they feel depressed because of their dyspareunia, she and her colleagues found.

Most respondents (88%) discussed their symptoms with health care providers (HCPs), and 85% did so with their ob.gyn. Among the other HCPs who respondents spoke with about their dyspareunia were primary care physicians, nurse practitioners, emergency department doctors, fertility specialists, and pain specialists.

Among the reasons given for avoiding discussions with HCPs about painful intercourse were embarrassment (34% of respondents), thinking nothing would help (26%), the physician was a man (5%), and a feeling that the provider was not understanding (3%).

Overall, 18% of respondents said they received no advice from their HCPs regarding how to deal with their dyspareunia, and 39% found nothing that their HCPs suggested to be effective.

Advice given by HCPs included surgery, lubricant use, over-the-counter pain medication, and trying different sexual positions. The percentages of respondents receiving this advice, and the percentages who considered the advice effective, respectively, were 46%, 25% for surgery; 32%, 21% for lubricant use; 36%, 18% for OTC medication; and 21%, 14% for trying different sexual positions, the investigators said.

Importantly, 42% of respondent said they felt it would be easier to discuss dyspareunia if their HCP initiated the subject.

The findings are notable given that 6%-10% of women of childbearing age are affected by endometriosis, and about 30% of those women have related dyspareunia – a “challenging symptom associated with lower sexual functioning, as well as lower self-esteem, and body image,” the investigators wrote.

The 24-question English-language survey was conducted online among women aged 19 years or older who reported having endometriosis and dyspareunia. Participants were recruited via a social network for women with endometriosis (MyEndometriosisTeam.com) and invited by e-mail to participate.

Of the 32,865 invited participants, 361 U.S.-based women and 277 women from outside the United States completed the survey. Most (83%) were aged 19-29 years.

In this online survey, the majority of women reported suboptimal communication with HCPs when seeking help for dyspareunia, the investigators said, concluding that “these results were similar between the U.S.- and non-U.S.–based women, highlighting the need for better medical communication between patients and HCPs, and better advice for patients regarding dyspareunia.”

Dr. Renzelli-Cain reported having no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – Many women with endometriosis experience dyspareunia, but they are largely unsatisfied when it comes to discussions with health care providers about their symptoms, the results of an online survey suggest.

Of 638 women with self-reported endometriosis who responded to the survey, 81% said they always or usually experience pain during intercourse, 51% described their pain as severe, and 49% said they experience pain lasting more than 24 hours, Roberta Renzelli-Cain, DO, reported during a poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“The results of our survey suggest that endometriosis-related pelvic pain and dyspareunia is a significant symptom, it is life changing, and it is frequently not addressed by health care providers,” said Dr. Renzelli-Cain, director of the West Virginia National Center of Excellence in Women’s Health and an ob.gyn. at West Virginia University, Morgantown.

In fact, survey responses suggested that dyspareunia has a marked impact on quality of life; 69% of respondents said they find sexual intercourse unpleasant, 31% said they always or usually avoid intercourse, 44% strongly agreed that dyspareunia has affected their relationship with their spouse or partner, 63% said they worry that their spouse or partner will leave, and 63% said they feel depressed because of their dyspareunia, she and her colleagues found.

Most respondents (88%) discussed their symptoms with health care providers (HCPs), and 85% did so with their ob.gyn. Among the other HCPs who respondents spoke with about their dyspareunia were primary care physicians, nurse practitioners, emergency department doctors, fertility specialists, and pain specialists.

Among the reasons given for avoiding discussions with HCPs about painful intercourse were embarrassment (34% of respondents), thinking nothing would help (26%), the physician was a man (5%), and a feeling that the provider was not understanding (3%).

Overall, 18% of respondents said they received no advice from their HCPs regarding how to deal with their dyspareunia, and 39% found nothing that their HCPs suggested to be effective.

Advice given by HCPs included surgery, lubricant use, over-the-counter pain medication, and trying different sexual positions. The percentages of respondents receiving this advice, and the percentages who considered the advice effective, respectively, were 46%, 25% for surgery; 32%, 21% for lubricant use; 36%, 18% for OTC medication; and 21%, 14% for trying different sexual positions, the investigators said.

Importantly, 42% of respondent said they felt it would be easier to discuss dyspareunia if their HCP initiated the subject.

The findings are notable given that 6%-10% of women of childbearing age are affected by endometriosis, and about 30% of those women have related dyspareunia – a “challenging symptom associated with lower sexual functioning, as well as lower self-esteem, and body image,” the investigators wrote.

The 24-question English-language survey was conducted online among women aged 19 years or older who reported having endometriosis and dyspareunia. Participants were recruited via a social network for women with endometriosis (MyEndometriosisTeam.com) and invited by e-mail to participate.

Of the 32,865 invited participants, 361 U.S.-based women and 277 women from outside the United States completed the survey. Most (83%) were aged 19-29 years.

In this online survey, the majority of women reported suboptimal communication with HCPs when seeking help for dyspareunia, the investigators said, concluding that “these results were similar between the U.S.- and non-U.S.–based women, highlighting the need for better medical communication between patients and HCPs, and better advice for patients regarding dyspareunia.”

Dr. Renzelli-Cain reported having no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – Many women with endometriosis experience dyspareunia, but they are largely unsatisfied when it comes to discussions with health care providers about their symptoms, the results of an online survey suggest.

Of 638 women with self-reported endometriosis who responded to the survey, 81% said they always or usually experience pain during intercourse, 51% described their pain as severe, and 49% said they experience pain lasting more than 24 hours, Roberta Renzelli-Cain, DO, reported during a poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“The results of our survey suggest that endometriosis-related pelvic pain and dyspareunia is a significant symptom, it is life changing, and it is frequently not addressed by health care providers,” said Dr. Renzelli-Cain, director of the West Virginia National Center of Excellence in Women’s Health and an ob.gyn. at West Virginia University, Morgantown.

In fact, survey responses suggested that dyspareunia has a marked impact on quality of life; 69% of respondents said they find sexual intercourse unpleasant, 31% said they always or usually avoid intercourse, 44% strongly agreed that dyspareunia has affected their relationship with their spouse or partner, 63% said they worry that their spouse or partner will leave, and 63% said they feel depressed because of their dyspareunia, she and her colleagues found.

Most respondents (88%) discussed their symptoms with health care providers (HCPs), and 85% did so with their ob.gyn. Among the other HCPs who respondents spoke with about their dyspareunia were primary care physicians, nurse practitioners, emergency department doctors, fertility specialists, and pain specialists.

Among the reasons given for avoiding discussions with HCPs about painful intercourse were embarrassment (34% of respondents), thinking nothing would help (26%), the physician was a man (5%), and a feeling that the provider was not understanding (3%).

Overall, 18% of respondents said they received no advice from their HCPs regarding how to deal with their dyspareunia, and 39% found nothing that their HCPs suggested to be effective.

Advice given by HCPs included surgery, lubricant use, over-the-counter pain medication, and trying different sexual positions. The percentages of respondents receiving this advice, and the percentages who considered the advice effective, respectively, were 46%, 25% for surgery; 32%, 21% for lubricant use; 36%, 18% for OTC medication; and 21%, 14% for trying different sexual positions, the investigators said.

Importantly, 42% of respondent said they felt it would be easier to discuss dyspareunia if their HCP initiated the subject.

The findings are notable given that 6%-10% of women of childbearing age are affected by endometriosis, and about 30% of those women have related dyspareunia – a “challenging symptom associated with lower sexual functioning, as well as lower self-esteem, and body image,” the investigators wrote.

The 24-question English-language survey was conducted online among women aged 19 years or older who reported having endometriosis and dyspareunia. Participants were recruited via a social network for women with endometriosis (MyEndometriosisTeam.com) and invited by e-mail to participate.

Of the 32,865 invited participants, 361 U.S.-based women and 277 women from outside the United States completed the survey. Most (83%) were aged 19-29 years.

In this online survey, the majority of women reported suboptimal communication with HCPs when seeking help for dyspareunia, the investigators said, concluding that “these results were similar between the U.S.- and non-U.S.–based women, highlighting the need for better medical communication between patients and HCPs, and better advice for patients regarding dyspareunia.”

Dr. Renzelli-Cain reported having no relevant financial disclosures.

[email protected]

Use of inhaled corticosteroids may lower the risk of lung cancer in patients with chronic obstructive pulmonary disease, and continued use may also reduce lung cancer risk, recent research from the European Respiratory Journal has shown.

“The appropriate use of [inhaled corticosteroids] ICS in [chronic obstructive pulmonary disease] COPD patients is often debated and not all patients might benefit from the use of ICS. The clinical benefits and risk of use in an individual patient must be weighed by the physician,” wrote Adam J.N. Raymakers, MSc, PhD, of the University of British Columbia’s Collaboration for Outcomes Research and Evaluation (CORE), Vancouver, B.C., and colleagues.

“This study, however, indicates that potential benefits may accrue from ICS use in COPD patients in terms of reduced lung cancer risk, and that sustained use may be associated with reduced risk of lung cancer.”

Dr. Raymakers and colleagues did an analysis of 39,676 patients with COPD (mean age, 70.7 years; 53% female) who received ICS between 1997 and 2007 and linked those patients to a registry of cancer patients in British Columbia. The linked databases included the Medical Services Plan (MSP) payment information file, Discharge Abstract Database (DAD), PharmaNet data file, and the British Columbia Cancer Registry (BCCR). The researchers determined a patient had COPD if he or she received three or more prescriptions related to COPD, while ICS exposure was analyzed in the context of a patient’s ICS exposure, cumulative duration, cumulative dose, and weighted cumulative duration and dose.

The analysis revealed 372,075 prescriptions for ICS were dispensed and 71.2% of the patients were “distinct users” of ICS, with patients filling a median of eight prescriptions at mean 5.2 years of follow-up. Fluticasone propionate was the most common ICS prescribed at a dose of 0.64 mg per day, and patients had median 60 days of ICS supplied per person.

Overall, there were 994 cases of lung cancer (2.5%), and exposure to ICS was linked to a 30% reduction in lung cancer risk (hazard ratio, 0.70; 95% confidence interval, 0.61-0.80), while recency-weighted duration of ICS exposure was linked to a 26% reduction in lung cancer risk (HR, 0.74; 95% CI, 0.66-0.87). There was a 43% reduced risk of lung cancer per gram of ICS when the data were measured by recency-weighted cumulative dosage.

In a multivariate analysis, ICS use was associated with a 30% reduction in risk of non–small cell lung cancer (HR, 0.70; 95% CI, 0.60-0.82), which the researchers said suggests ICS provides a protective effect for patients against lung cancer. “These results highlight the importance of properly identifying which patients might be at the highest risk of lung cancer, to enhance the therapeutic benefits of ICS in these COPD patients,” they wrote.

This study received funding from the Canadian Institutes of Health Research. The authors report no conflicts of interest.

SOURCE: Raymakers A, et al. Eur Respir J. 2019. doi: 10.1183/13993003.01257-2018.

Use of inhaled corticosteroids may lower the risk of lung cancer in patients with chronic obstructive pulmonary disease, and continued use may also reduce lung cancer risk, recent research from the European Respiratory Journal has shown.

“The appropriate use of [inhaled corticosteroids] ICS in [chronic obstructive pulmonary disease] COPD patients is often debated and not all patients might benefit from the use of ICS. The clinical benefits and risk of use in an individual patient must be weighed by the physician,” wrote Adam J.N. Raymakers, MSc, PhD, of the University of British Columbia’s Collaboration for Outcomes Research and Evaluation (CORE), Vancouver, B.C., and colleagues.

“This study, however, indicates that potential benefits may accrue from ICS use in COPD patients in terms of reduced lung cancer risk, and that sustained use may be associated with reduced risk of lung cancer.”

Dr. Raymakers and colleagues did an analysis of 39,676 patients with COPD (mean age, 70.7 years; 53% female) who received ICS between 1997 and 2007 and linked those patients to a registry of cancer patients in British Columbia. The linked databases included the Medical Services Plan (MSP) payment information file, Discharge Abstract Database (DAD), PharmaNet data file, and the British Columbia Cancer Registry (BCCR). The researchers determined a patient had COPD if he or she received three or more prescriptions related to COPD, while ICS exposure was analyzed in the context of a patient’s ICS exposure, cumulative duration, cumulative dose, and weighted cumulative duration and dose.

The analysis revealed 372,075 prescriptions for ICS were dispensed and 71.2% of the patients were “distinct users” of ICS, with patients filling a median of eight prescriptions at mean 5.2 years of follow-up. Fluticasone propionate was the most common ICS prescribed at a dose of 0.64 mg per day, and patients had median 60 days of ICS supplied per person.

Overall, there were 994 cases of lung cancer (2.5%), and exposure to ICS was linked to a 30% reduction in lung cancer risk (hazard ratio, 0.70; 95% confidence interval, 0.61-0.80), while recency-weighted duration of ICS exposure was linked to a 26% reduction in lung cancer risk (HR, 0.74; 95% CI, 0.66-0.87). There was a 43% reduced risk of lung cancer per gram of ICS when the data were measured by recency-weighted cumulative dosage.

In a multivariate analysis, ICS use was associated with a 30% reduction in risk of non–small cell lung cancer (HR, 0.70; 95% CI, 0.60-0.82), which the researchers said suggests ICS provides a protective effect for patients against lung cancer. “These results highlight the importance of properly identifying which patients might be at the highest risk of lung cancer, to enhance the therapeutic benefits of ICS in these COPD patients,” they wrote.

This study received funding from the Canadian Institutes of Health Research. The authors report no conflicts of interest.

SOURCE: Raymakers A, et al. Eur Respir J. 2019. doi: 10.1183/13993003.01257-2018.

Use of inhaled corticosteroids may lower the risk of lung cancer in patients with chronic obstructive pulmonary disease, and continued use may also reduce lung cancer risk, recent research from the European Respiratory Journal has shown.

“The appropriate use of [inhaled corticosteroids] ICS in [chronic obstructive pulmonary disease] COPD patients is often debated and not all patients might benefit from the use of ICS. The clinical benefits and risk of use in an individual patient must be weighed by the physician,” wrote Adam J.N. Raymakers, MSc, PhD, of the University of British Columbia’s Collaboration for Outcomes Research and Evaluation (CORE), Vancouver, B.C., and colleagues.

“This study, however, indicates that potential benefits may accrue from ICS use in COPD patients in terms of reduced lung cancer risk, and that sustained use may be associated with reduced risk of lung cancer.”

Dr. Raymakers and colleagues did an analysis of 39,676 patients with COPD (mean age, 70.7 years; 53% female) who received ICS between 1997 and 2007 and linked those patients to a registry of cancer patients in British Columbia. The linked databases included the Medical Services Plan (MSP) payment information file, Discharge Abstract Database (DAD), PharmaNet data file, and the British Columbia Cancer Registry (BCCR). The researchers determined a patient had COPD if he or she received three or more prescriptions related to COPD, while ICS exposure was analyzed in the context of a patient’s ICS exposure, cumulative duration, cumulative dose, and weighted cumulative duration and dose.

The analysis revealed 372,075 prescriptions for ICS were dispensed and 71.2% of the patients were “distinct users” of ICS, with patients filling a median of eight prescriptions at mean 5.2 years of follow-up. Fluticasone propionate was the most common ICS prescribed at a dose of 0.64 mg per day, and patients had median 60 days of ICS supplied per person.

Overall, there were 994 cases of lung cancer (2.5%), and exposure to ICS was linked to a 30% reduction in lung cancer risk (hazard ratio, 0.70; 95% confidence interval, 0.61-0.80), while recency-weighted duration of ICS exposure was linked to a 26% reduction in lung cancer risk (HR, 0.74; 95% CI, 0.66-0.87). There was a 43% reduced risk of lung cancer per gram of ICS when the data were measured by recency-weighted cumulative dosage.

In a multivariate analysis, ICS use was associated with a 30% reduction in risk of non–small cell lung cancer (HR, 0.70; 95% CI, 0.60-0.82), which the researchers said suggests ICS provides a protective effect for patients against lung cancer. “These results highlight the importance of properly identifying which patients might be at the highest risk of lung cancer, to enhance the therapeutic benefits of ICS in these COPD patients,” they wrote.

This study received funding from the Canadian Institutes of Health Research. The authors report no conflicts of interest.

SOURCE: Raymakers A, et al. Eur Respir J. 2019. doi: 10.1183/13993003.01257-2018.

Risk factors that have good test accuracy in recognizing pediatric cervical spinal injury (CSI) exist, and they can be incorporated into a clinical prediction rule that has the potential to greatly lower the need for cervical spine imaging during trauma evaluation, Julie C Leonard, MD, MPH, and associates reported in Pediatrics.

Fuse/thinkstockphotos.com

Though rare, cervical spine injuries in children lead to significant morbidity and mortality, and the vast majority of these children screened radiographically have no injury at all, which makes the inherent lifetime risk of malignancy from unnecessary radiation exposure troubling to many.

In their 2014-2016 prospective observational study in which 4,091 children aged 0-17 years were evaluated for blunt trauma in one of four U.S. tertiary care children’s hospitals, 2% had CSIs.

The mean age in the cohort was 9 years; the mean age of CSI patients was 11 years. Fully 39% of patients were under 8 years of age and 23 (1%) had CSIs. Among those with CSIs, more were boys, white, and non-Hispanic. Motor vehicle crash and sports-related injuries were reported to be the most common route of injury in all children.

The main goal of the study was to “establish the infrastructure for conducting a larger cohort study,” said Dr. Leonard of Ohio State University Nationwide Children’s Hospital in Columbus, and associates. They were successful in confirming the existence of an association between CSI and head injury. Specifically, the greatest independent associations with pediatric CSI were substantial head injury, namely basilar skull fracture; signs of traumatic brain injury, such as altered mental status; respiratory failure and intubation; and head-first impacts.

The authors were careful to point out that risk factors identified in their study differed from other studies focused on adult injury, specifically with regard to neck findings. They speculated that the increased neck and spine tenderness that commonly increase following restrictive supine positioning in a cervical collar on a rigid long board could play a key role. They also speculated that ED clinicians may be more likely to “defer aspects of the neck examination” in cases where children present wearing cervical collars, which limits assessment to self reporting.

As with adult evaluation, in which adult CSI prediction rules for cervical imaging depend upon determining the extent of normal mental status after blunt trauma, successful identification of pediatric candidates will require a similar set of CSI prediction rules. “Future development of a robust pediatric CSI prediction rule should be focused on stratification based on mental status because it may be meaningful in determining which children to triage to CT scan,” the investigators advised.

Future research exploring how these risk factors can be used to build a clear, pediatric CSI prediction rule that is prospective and observational in nature is crucial to improving the timeliness and accuracy of CSI diagnosis, Dr. Leonard and associates said.

In an accompanying editorial, Mark I. Neuman, MD, MPH and Rebekah C. Mannix, MD, MPH, noted that evidence uncovered by Leonard et al. will, no doubt, provide the conceptual foundation for a future multicenter trial that can establish effective criteria needed to consider the use of imaging when evaluating CSI in children.

Previously, the National Emergency X-Ray Utilization Study (NEXUS) was the largest prospective study of CSI that also included children. The Leonard et al. study includes a much higher proportion of children, 39% of whom were younger than 8 years of age. Although the sensitivities of the models used in this latest study are lower than for those used in the NEXUS study, the specificity is much higher at 46%-50%, which has noteworthy implications for classifying children at risk of CSI. “If validated, these findings have the potential to spare imaging in over one-third of children,” said Dr. Neuman and Dr. Mannix, both of the division of emergency medicine at Boston Children’s Hospital, and the department of pediatrics at Harvard Medical School, Boston.

“The complex and varying nature of CSI in children, the result of differences in the intrinsic biomechanics of the pediatric cervical spine, mechanism of injury, and variable presentations between younger and older children pose challenges for the development of a universal, simple, and highly sensitive clinical prediction rule,” they concluded.

The National Institutes of Health funded the study, and Dr. Leonard received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors had no relevant disclosures. There was no external funding for the accompanying editorial and Dr. Neuman and Dr. Mannix said they had no relevant disclosures.

SOURCE: Leonard J et al. Pediatrics. 2019;144(1):e20183221; Neuman MI et al. Pediatrics. 2019;144(1):e20184052.

Risk factors that have good test accuracy in recognizing pediatric cervical spinal injury (CSI) exist, and they can be incorporated into a clinical prediction rule that has the potential to greatly lower the need for cervical spine imaging during trauma evaluation, Julie C Leonard, MD, MPH, and associates reported in Pediatrics.

Fuse/thinkstockphotos.com

Though rare, cervical spine injuries in children lead to significant morbidity and mortality, and the vast majority of these children screened radiographically have no injury at all, which makes the inherent lifetime risk of malignancy from unnecessary radiation exposure troubling to many.

In their 2014-2016 prospective observational study in which 4,091 children aged 0-17 years were evaluated for blunt trauma in one of four U.S. tertiary care children’s hospitals, 2% had CSIs.

The mean age in the cohort was 9 years; the mean age of CSI patients was 11 years. Fully 39% of patients were under 8 years of age and 23 (1%) had CSIs. Among those with CSIs, more were boys, white, and non-Hispanic. Motor vehicle crash and sports-related injuries were reported to be the most common route of injury in all children.

The main goal of the study was to “establish the infrastructure for conducting a larger cohort study,” said Dr. Leonard of Ohio State University Nationwide Children’s Hospital in Columbus, and associates. They were successful in confirming the existence of an association between CSI and head injury. Specifically, the greatest independent associations with pediatric CSI were substantial head injury, namely basilar skull fracture; signs of traumatic brain injury, such as altered mental status; respiratory failure and intubation; and head-first impacts.

The authors were careful to point out that risk factors identified in their study differed from other studies focused on adult injury, specifically with regard to neck findings. They speculated that the increased neck and spine tenderness that commonly increase following restrictive supine positioning in a cervical collar on a rigid long board could play a key role. They also speculated that ED clinicians may be more likely to “defer aspects of the neck examination” in cases where children present wearing cervical collars, which limits assessment to self reporting.

As with adult evaluation, in which adult CSI prediction rules for cervical imaging depend upon determining the extent of normal mental status after blunt trauma, successful identification of pediatric candidates will require a similar set of CSI prediction rules. “Future development of a robust pediatric CSI prediction rule should be focused on stratification based on mental status because it may be meaningful in determining which children to triage to CT scan,” the investigators advised.

Future research exploring how these risk factors can be used to build a clear, pediatric CSI prediction rule that is prospective and observational in nature is crucial to improving the timeliness and accuracy of CSI diagnosis, Dr. Leonard and associates said.

In an accompanying editorial, Mark I. Neuman, MD, MPH and Rebekah C. Mannix, MD, MPH, noted that evidence uncovered by Leonard et al. will, no doubt, provide the conceptual foundation for a future multicenter trial that can establish effective criteria needed to consider the use of imaging when evaluating CSI in children.

Previously, the National Emergency X-Ray Utilization Study (NEXUS) was the largest prospective study of CSI that also included children. The Leonard et al. study includes a much higher proportion of children, 39% of whom were younger than 8 years of age. Although the sensitivities of the models used in this latest study are lower than for those used in the NEXUS study, the specificity is much higher at 46%-50%, which has noteworthy implications for classifying children at risk of CSI. “If validated, these findings have the potential to spare imaging in over one-third of children,” said Dr. Neuman and Dr. Mannix, both of the division of emergency medicine at Boston Children’s Hospital, and the department of pediatrics at Harvard Medical School, Boston.

“The complex and varying nature of CSI in children, the result of differences in the intrinsic biomechanics of the pediatric cervical spine, mechanism of injury, and variable presentations between younger and older children pose challenges for the development of a universal, simple, and highly sensitive clinical prediction rule,” they concluded.

The National Institutes of Health funded the study, and Dr. Leonard received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors had no relevant disclosures. There was no external funding for the accompanying editorial and Dr. Neuman and Dr. Mannix said they had no relevant disclosures.

SOURCE: Leonard J et al. Pediatrics. 2019;144(1):e20183221; Neuman MI et al. Pediatrics. 2019;144(1):e20184052.

Risk factors that have good test accuracy in recognizing pediatric cervical spinal injury (CSI) exist, and they can be incorporated into a clinical prediction rule that has the potential to greatly lower the need for cervical spine imaging during trauma evaluation, Julie C Leonard, MD, MPH, and associates reported in Pediatrics.

Fuse/thinkstockphotos.com

Though rare, cervical spine injuries in children lead to significant morbidity and mortality, and the vast majority of these children screened radiographically have no injury at all, which makes the inherent lifetime risk of malignancy from unnecessary radiation exposure troubling to many.

In their 2014-2016 prospective observational study in which 4,091 children aged 0-17 years were evaluated for blunt trauma in one of four U.S. tertiary care children’s hospitals, 2% had CSIs.

The mean age in the cohort was 9 years; the mean age of CSI patients was 11 years. Fully 39% of patients were under 8 years of age and 23 (1%) had CSIs. Among those with CSIs, more were boys, white, and non-Hispanic. Motor vehicle crash and sports-related injuries were reported to be the most common route of injury in all children.

The main goal of the study was to “establish the infrastructure for conducting a larger cohort study,” said Dr. Leonard of Ohio State University Nationwide Children’s Hospital in Columbus, and associates. They were successful in confirming the existence of an association between CSI and head injury. Specifically, the greatest independent associations with pediatric CSI were substantial head injury, namely basilar skull fracture; signs of traumatic brain injury, such as altered mental status; respiratory failure and intubation; and head-first impacts.

The authors were careful to point out that risk factors identified in their study differed from other studies focused on adult injury, specifically with regard to neck findings. They speculated that the increased neck and spine tenderness that commonly increase following restrictive supine positioning in a cervical collar on a rigid long board could play a key role. They also speculated that ED clinicians may be more likely to “defer aspects of the neck examination” in cases where children present wearing cervical collars, which limits assessment to self reporting.

As with adult evaluation, in which adult CSI prediction rules for cervical imaging depend upon determining the extent of normal mental status after blunt trauma, successful identification of pediatric candidates will require a similar set of CSI prediction rules. “Future development of a robust pediatric CSI prediction rule should be focused on stratification based on mental status because it may be meaningful in determining which children to triage to CT scan,” the investigators advised.

Future research exploring how these risk factors can be used to build a clear, pediatric CSI prediction rule that is prospective and observational in nature is crucial to improving the timeliness and accuracy of CSI diagnosis, Dr. Leonard and associates said.

In an accompanying editorial, Mark I. Neuman, MD, MPH and Rebekah C. Mannix, MD, MPH, noted that evidence uncovered by Leonard et al. will, no doubt, provide the conceptual foundation for a future multicenter trial that can establish effective criteria needed to consider the use of imaging when evaluating CSI in children.

Previously, the National Emergency X-Ray Utilization Study (NEXUS) was the largest prospective study of CSI that also included children. The Leonard et al. study includes a much higher proportion of children, 39% of whom were younger than 8 years of age. Although the sensitivities of the models used in this latest study are lower than for those used in the NEXUS study, the specificity is much higher at 46%-50%, which has noteworthy implications for classifying children at risk of CSI. “If validated, these findings have the potential to spare imaging in over one-third of children,” said Dr. Neuman and Dr. Mannix, both of the division of emergency medicine at Boston Children’s Hospital, and the department of pediatrics at Harvard Medical School, Boston.

“The complex and varying nature of CSI in children, the result of differences in the intrinsic biomechanics of the pediatric cervical spine, mechanism of injury, and variable presentations between younger and older children pose challenges for the development of a universal, simple, and highly sensitive clinical prediction rule,” they concluded.

The National Institutes of Health funded the study, and Dr. Leonard received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors had no relevant disclosures. There was no external funding for the accompanying editorial and Dr. Neuman and Dr. Mannix said they had no relevant disclosures.

SOURCE: Leonard J et al. Pediatrics. 2019;144(1):e20183221; Neuman MI et al. Pediatrics. 2019;144(1):e20184052.

AMSTERDAM – For patients with FLT3-mutated, relapsed or refractory acute myeloid leukemia (AML), gilteritinib (Xospata) offers better median overall survival than salvage chemotherapy, according to results from the phase 3 ADMIRAL trial.

Patients treated with gilteritinib also more often responded to therapy and entered remission, reported lead author Alexander Perl, MD, of the University of Pennsylvania, Philadelphia.

To overcome resistance mechanisms to existing FLT3 inhibitors, drug developers have been seeking agents with activity against both FLT3-ITD and FLT3-TKD mutations, Dr. Perl explained during his presentation at the annual congress of the European Hematology Association. “Gilteritinib is one of these agents,” he said, noting a unique mechanism of action that also may limit toxicity concerns associated with existing FLT3 inhibitors.

The international ADMIRAL trial involved 371 patients with FLT3-mutated AML who had not responded to induction therapy or were untreated after first relapse.

The population was randomized in a 2:1 ratio to receive either gilteritinib 120 mg/day or one of four salvage chemotherapy regimens: azacitidine (AZA), low-dose cytarabine (LoDAC), mitoxantrone/etoposide/cytarabine (MEC), or fludarabine/cytarabine/granulocyte colony-stimulating factor/idarubicin (FLAG-IDA).

Coprimary endpoints were overall survival and the combined rate of complete remission and complete remission with partial hematologic recovery (CR/CRh). Secondary endpoints were complete remission rate and event-free survival.

Demographic data showed that the median patient age was 62 years with a broad range (19-85 years). Most patients were positive for FLT3-ITD (88.4%), while fewer tested positive for FLT3-TKD (8.4%) or both mutations (1.9%). Relapsed AML was more common than refractory disease (60.6% vs. 39.4%).

The efficacy analysis revealed that patients treated with gilteritinib had a median overall survival of 9.3 months, significantly longer than the 5.6 months among those treated with salvage chemotherapy (hazard ratio for death = 0.637; P = .0007). The 1-year survival rate was 37.1% for the gilteritinib group, compared with 16.7% among those who received chemotherapy.

The superiority of gilteritinib was further supported by twofold higher rates of CR/CRh (34.0% vs. 15.3%) and complete remission (21.1% vs. 10.5%). Similarly, median event-free survival was significantly longer in the gilteritinib group (2.8 vs. 0.7 months). Most subgroups, such as age and sex, showed consistent benefit.

Overall, gilteritinib demonstrated a favorable safety profile. After adjusting for exposure duration, serious treatment related adverse events were more common in the chemotherapy group than the gilteritinib group (9.2% vs. 7.1%). Common grade 3 or higher adverse events related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%).

“We were able to give [gilteritinib] in an outpatient setting,” Dr. Perl said.

Although comparisons between responses based on mutation type were not possible, owing to small sample sizes, Dr. Perl highlighted that gilteritinib showed activity against both FLT3 mutation subtypes.

“This drug has been approved on the results of this study,” Dr. Perl said. “Because of this, we have a new standard of care for this population.”

The study was funded by Astellas. The investigators reported financial relationships with AbbVie, Bayer, Takeda, and other companies.

SOURCE: Perl A et al. EHA Congress, Abstract S876.

AMSTERDAM – For patients with FLT3-mutated, relapsed or refractory acute myeloid leukemia (AML), gilteritinib (Xospata) offers better median overall survival than salvage chemotherapy, according to results from the phase 3 ADMIRAL trial.

Patients treated with gilteritinib also more often responded to therapy and entered remission, reported lead author Alexander Perl, MD, of the University of Pennsylvania, Philadelphia.

To overcome resistance mechanisms to existing FLT3 inhibitors, drug developers have been seeking agents with activity against both FLT3-ITD and FLT3-TKD mutations, Dr. Perl explained during his presentation at the annual congress of the European Hematology Association. “Gilteritinib is one of these agents,” he said, noting a unique mechanism of action that also may limit toxicity concerns associated with existing FLT3 inhibitors.

The international ADMIRAL trial involved 371 patients with FLT3-mutated AML who had not responded to induction therapy or were untreated after first relapse.

The population was randomized in a 2:1 ratio to receive either gilteritinib 120 mg/day or one of four salvage chemotherapy regimens: azacitidine (AZA), low-dose cytarabine (LoDAC), mitoxantrone/etoposide/cytarabine (MEC), or fludarabine/cytarabine/granulocyte colony-stimulating factor/idarubicin (FLAG-IDA).

Coprimary endpoints were overall survival and the combined rate of complete remission and complete remission with partial hematologic recovery (CR/CRh). Secondary endpoints were complete remission rate and event-free survival.

Demographic data showed that the median patient age was 62 years with a broad range (19-85 years). Most patients were positive for FLT3-ITD (88.4%), while fewer tested positive for FLT3-TKD (8.4%) or both mutations (1.9%). Relapsed AML was more common than refractory disease (60.6% vs. 39.4%).

The efficacy analysis revealed that patients treated with gilteritinib had a median overall survival of 9.3 months, significantly longer than the 5.6 months among those treated with salvage chemotherapy (hazard ratio for death = 0.637; P = .0007). The 1-year survival rate was 37.1% for the gilteritinib group, compared with 16.7% among those who received chemotherapy.

The superiority of gilteritinib was further supported by twofold higher rates of CR/CRh (34.0% vs. 15.3%) and complete remission (21.1% vs. 10.5%). Similarly, median event-free survival was significantly longer in the gilteritinib group (2.8 vs. 0.7 months). Most subgroups, such as age and sex, showed consistent benefit.

Overall, gilteritinib demonstrated a favorable safety profile. After adjusting for exposure duration, serious treatment related adverse events were more common in the chemotherapy group than the gilteritinib group (9.2% vs. 7.1%). Common grade 3 or higher adverse events related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%).

“We were able to give [gilteritinib] in an outpatient setting,” Dr. Perl said.

Although comparisons between responses based on mutation type were not possible, owing to small sample sizes, Dr. Perl highlighted that gilteritinib showed activity against both FLT3 mutation subtypes.

“This drug has been approved on the results of this study,” Dr. Perl said. “Because of this, we have a new standard of care for this population.”

The study was funded by Astellas. The investigators reported financial relationships with AbbVie, Bayer, Takeda, and other companies.

SOURCE: Perl A et al. EHA Congress, Abstract S876.

AMSTERDAM – For patients with FLT3-mutated, relapsed or refractory acute myeloid leukemia (AML), gilteritinib (Xospata) offers better median overall survival than salvage chemotherapy, according to results from the phase 3 ADMIRAL trial.

Patients treated with gilteritinib also more often responded to therapy and entered remission, reported lead author Alexander Perl, MD, of the University of Pennsylvania, Philadelphia.

To overcome resistance mechanisms to existing FLT3 inhibitors, drug developers have been seeking agents with activity against both FLT3-ITD and FLT3-TKD mutations, Dr. Perl explained during his presentation at the annual congress of the European Hematology Association. “Gilteritinib is one of these agents,” he said, noting a unique mechanism of action that also may limit toxicity concerns associated with existing FLT3 inhibitors.

The international ADMIRAL trial involved 371 patients with FLT3-mutated AML who had not responded to induction therapy or were untreated after first relapse.

The population was randomized in a 2:1 ratio to receive either gilteritinib 120 mg/day or one of four salvage chemotherapy regimens: azacitidine (AZA), low-dose cytarabine (LoDAC), mitoxantrone/etoposide/cytarabine (MEC), or fludarabine/cytarabine/granulocyte colony-stimulating factor/idarubicin (FLAG-IDA).

Coprimary endpoints were overall survival and the combined rate of complete remission and complete remission with partial hematologic recovery (CR/CRh). Secondary endpoints were complete remission rate and event-free survival.

Demographic data showed that the median patient age was 62 years with a broad range (19-85 years). Most patients were positive for FLT3-ITD (88.4%), while fewer tested positive for FLT3-TKD (8.4%) or both mutations (1.9%). Relapsed AML was more common than refractory disease (60.6% vs. 39.4%).

The efficacy analysis revealed that patients treated with gilteritinib had a median overall survival of 9.3 months, significantly longer than the 5.6 months among those treated with salvage chemotherapy (hazard ratio for death = 0.637; P = .0007). The 1-year survival rate was 37.1% for the gilteritinib group, compared with 16.7% among those who received chemotherapy.

The superiority of gilteritinib was further supported by twofold higher rates of CR/CRh (34.0% vs. 15.3%) and complete remission (21.1% vs. 10.5%). Similarly, median event-free survival was significantly longer in the gilteritinib group (2.8 vs. 0.7 months). Most subgroups, such as age and sex, showed consistent benefit.

Overall, gilteritinib demonstrated a favorable safety profile. After adjusting for exposure duration, serious treatment related adverse events were more common in the chemotherapy group than the gilteritinib group (9.2% vs. 7.1%). Common grade 3 or higher adverse events related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%).

“We were able to give [gilteritinib] in an outpatient setting,” Dr. Perl said.

Although comparisons between responses based on mutation type were not possible, owing to small sample sizes, Dr. Perl highlighted that gilteritinib showed activity against both FLT3 mutation subtypes.

“This drug has been approved on the results of this study,” Dr. Perl said. “Because of this, we have a new standard of care for this population.”

The study was funded by Astellas. The investigators reported financial relationships with AbbVie, Bayer, Takeda, and other companies.

SOURCE: Perl A et al. EHA Congress, Abstract S876.