Bruce Jancin

SAN ANTONIO – An investigational muco-adherent swallowed formulation of budesonide developed specifically for treatment of eosinophilic esophagitis aced all primary and secondary endpoints in a pivotal, phase 3, double-blind, placebo-controlled randomized trial, Ikuo Hirano, MD, reported at the annual scientific meeting of the American College of Gastroenterology.

This is welcome news for patients with this chronic immune-mediated disease, for which no Food and Drug Administration–approved drug therapy exists yet.

“This is the first phase 3 trial to demonstrate efficacy using the validated Dysphagia Symptom Questionnaire, the first completed phase 3 trial of any medical therapeutic for eosinophilic esophagitis, and the largest clinical trial for eosinophilic esophagitis conducted to date,” declared Dr. Hirano, professor of medicine at Northwestern University in Chicago.

This was a 12-week induction therapy study including 318 adolescents and adults randomized 2:1 to 2 mg of budesonide oral suspension (BOS) or placebo twice daily. Patients were instructed not to eat or drink anything for 30 minutes afterward to avoid washing away the medication.

This was a severely affected patient population with high-level inflammatory activity: their mean baseline peak eosinophil count was 75 cells per high-power field, well above the diagnostic threshold of 50 eosinophils per high-power field. In keeping with a requirement for study participation, all patients had failed to respond to at least 6 weeks of high-dose proton pump inhibitor therapy. They also had to experience solid food dysphagia on at least 4 days per 2 weeks. More than 40% of subjects had previously undergone esophageal dilation.

One coprimary endpoint addressed histologic response, defined as 6 or fewer eosinophils per high-power field after 12 weeks of double-blind treatment. The histologic response rate was 53% in the BOS group and 1% in placebo-treated controls.

The other coprimary endpoint was symptom response as defined by at least a 30% reduction from baseline in the Dysphagia Symptom Questionnaire score. This was achieved in 53% of patients on BOS and 39% of controls.

The prespecified key secondary endpoint was the absolute reduction in Dysphagia Symptom Questionnaire score through week 12. From a mean baseline score of 30 out of a possible 84, the swallowed steroid recipients experienced a mean 13-point improvement, compared with a 9.1-improvement for those on placebo.

The topical budesonide group also did significantly better than placebo in terms of all other secondary endpoints. Endoscopic improvement as reflected in the mean Eosinophilic Esophagitis Reference Score was greater in the BOS group by a margin of 4 versus 2.2 points. A high-bar histologic response rate of no more than a single eosinophil per high-power field at week 12 was achieved in one-third of the BOS group and zero controls. The overall peak eosinophil count from baseline to week 12 dropped by an average of 55.2 cells per high-power field in the budesonide group, compared to a 7.6-eosinophil decrease in controls. And the proportion of patients with no more than 15 eosinophils per high-power field at week 12 was 62% with BOS, compared with 1% with placebo.

Treatment-emergent adverse events were similar in the two study arms and were mild to moderate in severity. Of note, however, the 3.8% incidence of esophageal candidiasis rate in the topical corticosteroid group was twice that seen in the placebo arm. Adrenal function as assessed by ACTH stimulation testing at baseline and 12 weeks was normal in 88% of the BOS group and 94% of controls.

Dr. Hirano noted that adrenal function will continue to be carefully monitored during an ongoing, phase 3, double-blind, placebo-controlled BOS maintenance study.

He reported receiving research funding from and serving as a consultant to Takeda, the study sponsor, as well as a handful of other pharmaceutical companies.

[email protected]

SAN ANTONIO – An investigational muco-adherent swallowed formulation of budesonide developed specifically for treatment of eosinophilic esophagitis aced all primary and secondary endpoints in a pivotal, phase 3, double-blind, placebo-controlled randomized trial, Ikuo Hirano, MD, reported at the annual scientific meeting of the American College of Gastroenterology.

This is welcome news for patients with this chronic immune-mediated disease, for which no Food and Drug Administration–approved drug therapy exists yet.

“This is the first phase 3 trial to demonstrate efficacy using the validated Dysphagia Symptom Questionnaire, the first completed phase 3 trial of any medical therapeutic for eosinophilic esophagitis, and the largest clinical trial for eosinophilic esophagitis conducted to date,” declared Dr. Hirano, professor of medicine at Northwestern University in Chicago.

This was a 12-week induction therapy study including 318 adolescents and adults randomized 2:1 to 2 mg of budesonide oral suspension (BOS) or placebo twice daily. Patients were instructed not to eat or drink anything for 30 minutes afterward to avoid washing away the medication.

This was a severely affected patient population with high-level inflammatory activity: their mean baseline peak eosinophil count was 75 cells per high-power field, well above the diagnostic threshold of 50 eosinophils per high-power field. In keeping with a requirement for study participation, all patients had failed to respond to at least 6 weeks of high-dose proton pump inhibitor therapy. They also had to experience solid food dysphagia on at least 4 days per 2 weeks. More than 40% of subjects had previously undergone esophageal dilation.

One coprimary endpoint addressed histologic response, defined as 6 or fewer eosinophils per high-power field after 12 weeks of double-blind treatment. The histologic response rate was 53% in the BOS group and 1% in placebo-treated controls.

The other coprimary endpoint was symptom response as defined by at least a 30% reduction from baseline in the Dysphagia Symptom Questionnaire score. This was achieved in 53% of patients on BOS and 39% of controls.

The prespecified key secondary endpoint was the absolute reduction in Dysphagia Symptom Questionnaire score through week 12. From a mean baseline score of 30 out of a possible 84, the swallowed steroid recipients experienced a mean 13-point improvement, compared with a 9.1-improvement for those on placebo.

The topical budesonide group also did significantly better than placebo in terms of all other secondary endpoints. Endoscopic improvement as reflected in the mean Eosinophilic Esophagitis Reference Score was greater in the BOS group by a margin of 4 versus 2.2 points. A high-bar histologic response rate of no more than a single eosinophil per high-power field at week 12 was achieved in one-third of the BOS group and zero controls. The overall peak eosinophil count from baseline to week 12 dropped by an average of 55.2 cells per high-power field in the budesonide group, compared to a 7.6-eosinophil decrease in controls. And the proportion of patients with no more than 15 eosinophils per high-power field at week 12 was 62% with BOS, compared with 1% with placebo.

Treatment-emergent adverse events were similar in the two study arms and were mild to moderate in severity. Of note, however, the 3.8% incidence of esophageal candidiasis rate in the topical corticosteroid group was twice that seen in the placebo arm. Adrenal function as assessed by ACTH stimulation testing at baseline and 12 weeks was normal in 88% of the BOS group and 94% of controls.

Dr. Hirano noted that adrenal function will continue to be carefully monitored during an ongoing, phase 3, double-blind, placebo-controlled BOS maintenance study.

He reported receiving research funding from and serving as a consultant to Takeda, the study sponsor, as well as a handful of other pharmaceutical companies.

[email protected]

SAN ANTONIO – An investigational muco-adherent swallowed formulation of budesonide developed specifically for treatment of eosinophilic esophagitis aced all primary and secondary endpoints in a pivotal, phase 3, double-blind, placebo-controlled randomized trial, Ikuo Hirano, MD, reported at the annual scientific meeting of the American College of Gastroenterology.

This is welcome news for patients with this chronic immune-mediated disease, for which no Food and Drug Administration–approved drug therapy exists yet.

“This is the first phase 3 trial to demonstrate efficacy using the validated Dysphagia Symptom Questionnaire, the first completed phase 3 trial of any medical therapeutic for eosinophilic esophagitis, and the largest clinical trial for eosinophilic esophagitis conducted to date,” declared Dr. Hirano, professor of medicine at Northwestern University in Chicago.

This was a 12-week induction therapy study including 318 adolescents and adults randomized 2:1 to 2 mg of budesonide oral suspension (BOS) or placebo twice daily. Patients were instructed not to eat or drink anything for 30 minutes afterward to avoid washing away the medication.

This was a severely affected patient population with high-level inflammatory activity: their mean baseline peak eosinophil count was 75 cells per high-power field, well above the diagnostic threshold of 50 eosinophils per high-power field. In keeping with a requirement for study participation, all patients had failed to respond to at least 6 weeks of high-dose proton pump inhibitor therapy. They also had to experience solid food dysphagia on at least 4 days per 2 weeks. More than 40% of subjects had previously undergone esophageal dilation.

One coprimary endpoint addressed histologic response, defined as 6 or fewer eosinophils per high-power field after 12 weeks of double-blind treatment. The histologic response rate was 53% in the BOS group and 1% in placebo-treated controls.

The other coprimary endpoint was symptom response as defined by at least a 30% reduction from baseline in the Dysphagia Symptom Questionnaire score. This was achieved in 53% of patients on BOS and 39% of controls.

The prespecified key secondary endpoint was the absolute reduction in Dysphagia Symptom Questionnaire score through week 12. From a mean baseline score of 30 out of a possible 84, the swallowed steroid recipients experienced a mean 13-point improvement, compared with a 9.1-improvement for those on placebo.

The topical budesonide group also did significantly better than placebo in terms of all other secondary endpoints. Endoscopic improvement as reflected in the mean Eosinophilic Esophagitis Reference Score was greater in the BOS group by a margin of 4 versus 2.2 points. A high-bar histologic response rate of no more than a single eosinophil per high-power field at week 12 was achieved in one-third of the BOS group and zero controls. The overall peak eosinophil count from baseline to week 12 dropped by an average of 55.2 cells per high-power field in the budesonide group, compared to a 7.6-eosinophil decrease in controls. And the proportion of patients with no more than 15 eosinophils per high-power field at week 12 was 62% with BOS, compared with 1% with placebo.

Treatment-emergent adverse events were similar in the two study arms and were mild to moderate in severity. Of note, however, the 3.8% incidence of esophageal candidiasis rate in the topical corticosteroid group was twice that seen in the placebo arm. Adrenal function as assessed by ACTH stimulation testing at baseline and 12 weeks was normal in 88% of the BOS group and 94% of controls.

Dr. Hirano noted that adrenal function will continue to be carefully monitored during an ongoing, phase 3, double-blind, placebo-controlled BOS maintenance study.

He reported receiving research funding from and serving as a consultant to Takeda, the study sponsor, as well as a handful of other pharmaceutical companies.

[email protected]

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

[email protected]

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

[email protected]

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

[email protected]

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

MADRID – Repigmentation in patients with vitiligo documented at 24 weeks continued to increase up to 1 year, in a randomized clinical trial of ruxolitinib cream for the treatment of vitiligo, Amit G. Pandya, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“I have been waiting 30 years for the first clinical trial for vitiligo. I know many of you dermatologists have been waiting for something for vitiligo, so I’m happy to present the results of the first randomized, placebo-controlled, double-blind, prospective trial of a topical agent in history for vitiligo,” said Dr. Pandya, who was clearly overjoyed to present the final results of the 52-week trial.

Ruxolitinib is a Janus kinase (JAK) 1 and 2 inhibitor. Topical ruxolitinib is under study for vitiligo because this chronic autoimmune disease targeting melanocytes is now recognized as being driven by signaling through the JAK 1/2 pathways.

The interim 24-week results of the phase 2 trial, presented earlier in the year at the World Congress of Dermatology in Milan, showed significant repigmentation with ruxolitinib cream. Dr. Pandya’s key message at EADV 2019 was that continued treatment out to a year brought substantial further improvement, and with a benign safety profile indistinguishable from vehicle control.

“We see a tremendous difference between 6 months and 1 year,” said Dr. Pandya, professor of dermatology at the University of Texas, Dallas. “For the first time, we dare talk about F-VASI75 [Facial Vitiligo Area Scoring Index] and F-VASI90 responses. We don’t usually tell patients that they can get 75% or 90% of their color back, and yet the week-52 F-VASI75 rate was 51.5%, up from 30.3% at week 24. And the F-VASI90 response was 33.3%, versus 12.1% at week 24.”

F-VASI is measured using the patient’s hand, which is typically equivalent to about 1% of body surface area. The mean baseline F-VASI was 1.26% in this study of 157 mostly middle-aged adults with longstanding vitiligo of a mean 14-year duration. That’s fairly severe vitiligo, since the total face occupies only about 4% of total body surface area.

The primary study endpoint was achievement of greater than 50% repigmentation in the F-VASI, or an F-VASI50 response. Under double-blind conditions at 52 weeks in the group randomized to 1.5% ruxolitinib cream twice a day, the highest dose used in the trial, the F-VASI50 rate was 57.6%. That’s up from a week-24 F-VASI50 of 45.5%, and a week-34 response rate of 51.5%.

A key secondary endpoint was T-VASI50, reflecting the total body response.

“Patients don’t just want their face to be better, they want their chest, arms, elbows, knees, hands, and feet to be better,” the dermatologist commented.

The week-52 T-VASI50 rate was 36.4%, up substantially from 12.1% at week 24. And that week-52 T-VASI50 rate probably underestimates the full potential benefit. That’s because a safety-based study rule prohibited patients from applying the cream to more than 20% of their body surface area. Adverse effects reported for oral ruxolitinib, approved for treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease, include thrombocytopenia and anemia.

“In this early study we didn’t want to take a chance of systemic absorption with serum levels that would potentially affect the bone marrow,” Dr. Pandya explained.

He noted that 57 study participants had a baseline T-VASI greater than 20% of their body surface area and thus weren’t able to treat all of their disease. In the 100 patients with a vitiligo-involved total body surface area of 20% or less, however, the week-52 T-VASI50 reached 45%, compared with 20% at week 24.

Another prespecified secondary endpoint was the proportion of patients who received a facial physician’s global assessment of clear or almost clear. About 21% of patients in the highest-dose group achieved this milestone at 52 weeks.

A phase 3, randomized, controlled trial of ruxolitinib cream is ongoing and should be completed next year. Dr. Pandya reported receiving research funding from and serving as a consultant to Incyte, the study sponsor. He has similar financial relationships with Pfizer, Aclaris Therapeutics, and the Immune Tolerance Network.

[email protected]

MADRID – Repigmentation in patients with vitiligo documented at 24 weeks continued to increase up to 1 year, in a randomized clinical trial of ruxolitinib cream for the treatment of vitiligo, Amit G. Pandya, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“I have been waiting 30 years for the first clinical trial for vitiligo. I know many of you dermatologists have been waiting for something for vitiligo, so I’m happy to present the results of the first randomized, placebo-controlled, double-blind, prospective trial of a topical agent in history for vitiligo,” said Dr. Pandya, who was clearly overjoyed to present the final results of the 52-week trial.

Ruxolitinib is a Janus kinase (JAK) 1 and 2 inhibitor. Topical ruxolitinib is under study for vitiligo because this chronic autoimmune disease targeting melanocytes is now recognized as being driven by signaling through the JAK 1/2 pathways.

The interim 24-week results of the phase 2 trial, presented earlier in the year at the World Congress of Dermatology in Milan, showed significant repigmentation with ruxolitinib cream. Dr. Pandya’s key message at EADV 2019 was that continued treatment out to a year brought substantial further improvement, and with a benign safety profile indistinguishable from vehicle control.

“We see a tremendous difference between 6 months and 1 year,” said Dr. Pandya, professor of dermatology at the University of Texas, Dallas. “For the first time, we dare talk about F-VASI75 [Facial Vitiligo Area Scoring Index] and F-VASI90 responses. We don’t usually tell patients that they can get 75% or 90% of their color back, and yet the week-52 F-VASI75 rate was 51.5%, up from 30.3% at week 24. And the F-VASI90 response was 33.3%, versus 12.1% at week 24.”

F-VASI is measured using the patient’s hand, which is typically equivalent to about 1% of body surface area. The mean baseline F-VASI was 1.26% in this study of 157 mostly middle-aged adults with longstanding vitiligo of a mean 14-year duration. That’s fairly severe vitiligo, since the total face occupies only about 4% of total body surface area.

The primary study endpoint was achievement of greater than 50% repigmentation in the F-VASI, or an F-VASI50 response. Under double-blind conditions at 52 weeks in the group randomized to 1.5% ruxolitinib cream twice a day, the highest dose used in the trial, the F-VASI50 rate was 57.6%. That’s up from a week-24 F-VASI50 of 45.5%, and a week-34 response rate of 51.5%.

A key secondary endpoint was T-VASI50, reflecting the total body response.

“Patients don’t just want their face to be better, they want their chest, arms, elbows, knees, hands, and feet to be better,” the dermatologist commented.

The week-52 T-VASI50 rate was 36.4%, up substantially from 12.1% at week 24. And that week-52 T-VASI50 rate probably underestimates the full potential benefit. That’s because a safety-based study rule prohibited patients from applying the cream to more than 20% of their body surface area. Adverse effects reported for oral ruxolitinib, approved for treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease, include thrombocytopenia and anemia.

“In this early study we didn’t want to take a chance of systemic absorption with serum levels that would potentially affect the bone marrow,” Dr. Pandya explained.

He noted that 57 study participants had a baseline T-VASI greater than 20% of their body surface area and thus weren’t able to treat all of their disease. In the 100 patients with a vitiligo-involved total body surface area of 20% or less, however, the week-52 T-VASI50 reached 45%, compared with 20% at week 24.

Another prespecified secondary endpoint was the proportion of patients who received a facial physician’s global assessment of clear or almost clear. About 21% of patients in the highest-dose group achieved this milestone at 52 weeks.

A phase 3, randomized, controlled trial of ruxolitinib cream is ongoing and should be completed next year. Dr. Pandya reported receiving research funding from and serving as a consultant to Incyte, the study sponsor. He has similar financial relationships with Pfizer, Aclaris Therapeutics, and the Immune Tolerance Network.

[email protected]

MADRID – Repigmentation in patients with vitiligo documented at 24 weeks continued to increase up to 1 year, in a randomized clinical trial of ruxolitinib cream for the treatment of vitiligo, Amit G. Pandya, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“I have been waiting 30 years for the first clinical trial for vitiligo. I know many of you dermatologists have been waiting for something for vitiligo, so I’m happy to present the results of the first randomized, placebo-controlled, double-blind, prospective trial of a topical agent in history for vitiligo,” said Dr. Pandya, who was clearly overjoyed to present the final results of the 52-week trial.

Ruxolitinib is a Janus kinase (JAK) 1 and 2 inhibitor. Topical ruxolitinib is under study for vitiligo because this chronic autoimmune disease targeting melanocytes is now recognized as being driven by signaling through the JAK 1/2 pathways.

The interim 24-week results of the phase 2 trial, presented earlier in the year at the World Congress of Dermatology in Milan, showed significant repigmentation with ruxolitinib cream. Dr. Pandya’s key message at EADV 2019 was that continued treatment out to a year brought substantial further improvement, and with a benign safety profile indistinguishable from vehicle control.

“We see a tremendous difference between 6 months and 1 year,” said Dr. Pandya, professor of dermatology at the University of Texas, Dallas. “For the first time, we dare talk about F-VASI75 [Facial Vitiligo Area Scoring Index] and F-VASI90 responses. We don’t usually tell patients that they can get 75% or 90% of their color back, and yet the week-52 F-VASI75 rate was 51.5%, up from 30.3% at week 24. And the F-VASI90 response was 33.3%, versus 12.1% at week 24.”

F-VASI is measured using the patient’s hand, which is typically equivalent to about 1% of body surface area. The mean baseline F-VASI was 1.26% in this study of 157 mostly middle-aged adults with longstanding vitiligo of a mean 14-year duration. That’s fairly severe vitiligo, since the total face occupies only about 4% of total body surface area.

The primary study endpoint was achievement of greater than 50% repigmentation in the F-VASI, or an F-VASI50 response. Under double-blind conditions at 52 weeks in the group randomized to 1.5% ruxolitinib cream twice a day, the highest dose used in the trial, the F-VASI50 rate was 57.6%. That’s up from a week-24 F-VASI50 of 45.5%, and a week-34 response rate of 51.5%.

A key secondary endpoint was T-VASI50, reflecting the total body response.

“Patients don’t just want their face to be better, they want their chest, arms, elbows, knees, hands, and feet to be better,” the dermatologist commented.

The week-52 T-VASI50 rate was 36.4%, up substantially from 12.1% at week 24. And that week-52 T-VASI50 rate probably underestimates the full potential benefit. That’s because a safety-based study rule prohibited patients from applying the cream to more than 20% of their body surface area. Adverse effects reported for oral ruxolitinib, approved for treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease, include thrombocytopenia and anemia.

“In this early study we didn’t want to take a chance of systemic absorption with serum levels that would potentially affect the bone marrow,” Dr. Pandya explained.

He noted that 57 study participants had a baseline T-VASI greater than 20% of their body surface area and thus weren’t able to treat all of their disease. In the 100 patients with a vitiligo-involved total body surface area of 20% or less, however, the week-52 T-VASI50 reached 45%, compared with 20% at week 24.

Another prespecified secondary endpoint was the proportion of patients who received a facial physician’s global assessment of clear or almost clear. About 21% of patients in the highest-dose group achieved this milestone at 52 weeks.

A phase 3, randomized, controlled trial of ruxolitinib cream is ongoing and should be completed next year. Dr. Pandya reported receiving research funding from and serving as a consultant to Incyte, the study sponsor. He has similar financial relationships with Pfizer, Aclaris Therapeutics, and the Immune Tolerance Network.

[email protected]

MADRID – Psoriasis patients aged 65 years and older are at more than twice the risk of serious bacterial and opportunistic infections, compared with younger patients, but that risk is not further elevated by being on biologic agents, Joseph F. Merola, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

He presented a large, propensity score–matched comparative safety study, which demonstrated that the infection risk of older psoriasis patients on biologics was not significantly different from that of similar patients on nonbiologic systemic medications or phototherapy. The study implications, he said, are clear: When moderate to severe psoriasis warrants consideration of highly effective biologic therapies, that therapeutic option shouldn’t be taken off the table on the basis of a mistaken belief that biologics pose a greater infection risk just because the affected patient is over age 65 years.

“We really think that older patients should be offered treatments at the same level of disease control as all the rest of our psoriasis patients, in the context of shared decision making,” said Dr. Merola, a dermatologist and rheumatologist who is the director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston.

The study utilized longitudinal claims data from a very large U.S. database covering the years 2003-2017. Among the 185 million covered lives were 1.1 million individuals with psoriasis, including 150,000 aged 65 years or older. After excluding older psoriasis patients with comorbid cancer or autoimmune disease, the investigators were left with 11,218 older psoriasis patients initiating systemic therapy for the first time and therefore eligible for propensity score matching using a highly accurate proprietary platform. The final study population consisted of 2,795 older psoriasis patients newly initiating biologic therapy, 2,795 others newly initiating nonbiologic systemic agents, and 2,529 seniors starting phototherapy. The matching was based upon factors including age, sex, prior infections, comorbid psoriatic arthritis, diabetes, and obesity.

The primary study endpoint was the rate of serious bacterial or opportunistic infections requiring hospitalization during the first 6 months of treatment. The bottom line: The rates were closely similar across all three groups, with the most common serious infections being pneumonia and cellulitis.

In contrast, among a population of 115,047 senior psoriasis patients who never used systemic therapy, the risk of serious infection was 12.2 events per 1,000 patients over 6 months, compared with 5.3 events in 120,174 matched controls without psoriasis. That translates to a 2.24-fold increased risk.

One audience member commented that a limitation of the study was that all biologics were lumped together. He would expect that the tumor necrosis factor inhibitors, for example, would be associated with a significantly higher serious infection risk than biologics with other targets.

Dr. Merola conceded the point, adding that the investigators are trying to reanalyze the data in a more granular way to address that shortcoming. Other study limitations included an inability to access the specific doses of systemic treatments used or to stratify patients by disease severity.

Another audience member noted that dermatologists often reassure surgeons that there’s no increased risk of infection associated with psoriasis when in fact there is increased risk in older psoriasis patients, according to these new data.

“We’re not trying to send a message to surgeons to withhold a knee transplant because of a psoriasis plaque over the knee,” Dr. Merola replied. “I think we’ve all been there; we’ve all fought that battle.” Based on the data, he said, he would advise that “our patients who need to be on systemics should remain appropriately on systemics as we see fit.”

The study was entirely funded by Brigham and Women’s Hospital. Dr. Merola reported serving as a consultant to and/or recipient of research grants from nearly two dozen pharmaceutical companies.

[email protected]

MADRID – Psoriasis patients aged 65 years and older are at more than twice the risk of serious bacterial and opportunistic infections, compared with younger patients, but that risk is not further elevated by being on biologic agents, Joseph F. Merola, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

He presented a large, propensity score–matched comparative safety study, which demonstrated that the infection risk of older psoriasis patients on biologics was not significantly different from that of similar patients on nonbiologic systemic medications or phototherapy. The study implications, he said, are clear: When moderate to severe psoriasis warrants consideration of highly effective biologic therapies, that therapeutic option shouldn’t be taken off the table on the basis of a mistaken belief that biologics pose a greater infection risk just because the affected patient is over age 65 years.

“We really think that older patients should be offered treatments at the same level of disease control as all the rest of our psoriasis patients, in the context of shared decision making,” said Dr. Merola, a dermatologist and rheumatologist who is the director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston.

The study utilized longitudinal claims data from a very large U.S. database covering the years 2003-2017. Among the 185 million covered lives were 1.1 million individuals with psoriasis, including 150,000 aged 65 years or older. After excluding older psoriasis patients with comorbid cancer or autoimmune disease, the investigators were left with 11,218 older psoriasis patients initiating systemic therapy for the first time and therefore eligible for propensity score matching using a highly accurate proprietary platform. The final study population consisted of 2,795 older psoriasis patients newly initiating biologic therapy, 2,795 others newly initiating nonbiologic systemic agents, and 2,529 seniors starting phototherapy. The matching was based upon factors including age, sex, prior infections, comorbid psoriatic arthritis, diabetes, and obesity.

The primary study endpoint was the rate of serious bacterial or opportunistic infections requiring hospitalization during the first 6 months of treatment. The bottom line: The rates were closely similar across all three groups, with the most common serious infections being pneumonia and cellulitis.

In contrast, among a population of 115,047 senior psoriasis patients who never used systemic therapy, the risk of serious infection was 12.2 events per 1,000 patients over 6 months, compared with 5.3 events in 120,174 matched controls without psoriasis. That translates to a 2.24-fold increased risk.

One audience member commented that a limitation of the study was that all biologics were lumped together. He would expect that the tumor necrosis factor inhibitors, for example, would be associated with a significantly higher serious infection risk than biologics with other targets.

Dr. Merola conceded the point, adding that the investigators are trying to reanalyze the data in a more granular way to address that shortcoming. Other study limitations included an inability to access the specific doses of systemic treatments used or to stratify patients by disease severity.

Another audience member noted that dermatologists often reassure surgeons that there’s no increased risk of infection associated with psoriasis when in fact there is increased risk in older psoriasis patients, according to these new data.

“We’re not trying to send a message to surgeons to withhold a knee transplant because of a psoriasis plaque over the knee,” Dr. Merola replied. “I think we’ve all been there; we’ve all fought that battle.” Based on the data, he said, he would advise that “our patients who need to be on systemics should remain appropriately on systemics as we see fit.”

The study was entirely funded by Brigham and Women’s Hospital. Dr. Merola reported serving as a consultant to and/or recipient of research grants from nearly two dozen pharmaceutical companies.

[email protected]

MADRID – Psoriasis patients aged 65 years and older are at more than twice the risk of serious bacterial and opportunistic infections, compared with younger patients, but that risk is not further elevated by being on biologic agents, Joseph F. Merola, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

He presented a large, propensity score–matched comparative safety study, which demonstrated that the infection risk of older psoriasis patients on biologics was not significantly different from that of similar patients on nonbiologic systemic medications or phototherapy. The study implications, he said, are clear: When moderate to severe psoriasis warrants consideration of highly effective biologic therapies, that therapeutic option shouldn’t be taken off the table on the basis of a mistaken belief that biologics pose a greater infection risk just because the affected patient is over age 65 years.

“We really think that older patients should be offered treatments at the same level of disease control as all the rest of our psoriasis patients, in the context of shared decision making,” said Dr. Merola, a dermatologist and rheumatologist who is the director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston.

The study utilized longitudinal claims data from a very large U.S. database covering the years 2003-2017. Among the 185 million covered lives were 1.1 million individuals with psoriasis, including 150,000 aged 65 years or older. After excluding older psoriasis patients with comorbid cancer or autoimmune disease, the investigators were left with 11,218 older psoriasis patients initiating systemic therapy for the first time and therefore eligible for propensity score matching using a highly accurate proprietary platform. The final study population consisted of 2,795 older psoriasis patients newly initiating biologic therapy, 2,795 others newly initiating nonbiologic systemic agents, and 2,529 seniors starting phototherapy. The matching was based upon factors including age, sex, prior infections, comorbid psoriatic arthritis, diabetes, and obesity.

The primary study endpoint was the rate of serious bacterial or opportunistic infections requiring hospitalization during the first 6 months of treatment. The bottom line: The rates were closely similar across all three groups, with the most common serious infections being pneumonia and cellulitis.

In contrast, among a population of 115,047 senior psoriasis patients who never used systemic therapy, the risk of serious infection was 12.2 events per 1,000 patients over 6 months, compared with 5.3 events in 120,174 matched controls without psoriasis. That translates to a 2.24-fold increased risk.

One audience member commented that a limitation of the study was that all biologics were lumped together. He would expect that the tumor necrosis factor inhibitors, for example, would be associated with a significantly higher serious infection risk than biologics with other targets.

Dr. Merola conceded the point, adding that the investigators are trying to reanalyze the data in a more granular way to address that shortcoming. Other study limitations included an inability to access the specific doses of systemic treatments used or to stratify patients by disease severity.

Another audience member noted that dermatologists often reassure surgeons that there’s no increased risk of infection associated with psoriasis when in fact there is increased risk in older psoriasis patients, according to these new data.

“We’re not trying to send a message to surgeons to withhold a knee transplant because of a psoriasis plaque over the knee,” Dr. Merola replied. “I think we’ve all been there; we’ve all fought that battle.” Based on the data, he said, he would advise that “our patients who need to be on systemics should remain appropriately on systemics as we see fit.”

The study was entirely funded by Brigham and Women’s Hospital. Dr. Merola reported serving as a consultant to and/or recipient of research grants from nearly two dozen pharmaceutical companies.

[email protected]

COPENHAGEN – Sleep problems during pregnancy are a risk factor for subsequent clinically significant postnatal depressive symptoms, Tiina Paunio, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

“I think it is very important to understand that we need to screen pregnant women for sleep problems, even those without a history of depression, so we can have early treatment of insomnia – and also depression – because postnatal maternal depression is very much a risk for the child during a vulnerable period for development,” said Dr. Paunio, professor of psychiatry at the University of Helsinki.

She was a coinvestigator in a prospective study of the Finnish CHILD-SLEEP longitudinal birth cohort in which 1,398 women completed the Basic Nordic Sleep Questionnaire and the 10-item version of the Center for Epidemiological Studies Depression Scale (CES-D) at about gestational week 32 and again around 3 months following delivery. Postnatal depressiveness as defined by a CES-D score of at least 10 points was present in 10.3% of the mothers. After adjusting for prenatal depressiveness and other potential confounders, the investigators found that tiredness during the day, poor general sleep quality, getting less than 6 hours of sleep, taking longer than 20 minutes to fall asleep, and sleep loss of 2 hours or more per night during pregnancy were each associated with clinically significant postnatal depressive symptoms, with odds ratios of 1.87-2.19.

The full details of the study have been published (Arch Womens Ment Health. 2019 Jun;22[3]:327-37).

The impetus for this study of sleep problems in pregnancy as a predictor of postnatal depressive symptoms was a body of evidence linking insomnia to depression in both men and women. But it turns out that insomnia is a significant predictor of later onset of a wide variety of psychiatric disorders, not only depression, as highlighted in a recent systematic review and meta-analysis conducted by an international team of investigators, Dr. Paunio observed.

Baseline insomnia symptoms were associated with a 183% increased risk of later onset of depression, a 223% increased risk of anxiety, a 35%greater risk of alcohol abuse, and a 28% increased risk of psychosis. However, the insomnia/psychosis link must be viewed as tentative, as it was examined in only a single published study. The investigators rated the overall risk of bias in the studies included in their meta-analysis as moderate (Sleep Med Rev. 2019 Feb;43:96-105).

For Dr. Paunio, these findings suggest that interventional studies of early and effective treatment of insomnia as a potential means of preventing psychiatric disorders are in order.

She reported receiving research funding from the Academy of Finland, the Gyllenberg Foundation, and Finska Lakaresallskapet.

[email protected]

COPENHAGEN – Sleep problems during pregnancy are a risk factor for subsequent clinically significant postnatal depressive symptoms, Tiina Paunio, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

“I think it is very important to understand that we need to screen pregnant women for sleep problems, even those without a history of depression, so we can have early treatment of insomnia – and also depression – because postnatal maternal depression is very much a risk for the child during a vulnerable period for development,” said Dr. Paunio, professor of psychiatry at the University of Helsinki.

She was a coinvestigator in a prospective study of the Finnish CHILD-SLEEP longitudinal birth cohort in which 1,398 women completed the Basic Nordic Sleep Questionnaire and the 10-item version of the Center for Epidemiological Studies Depression Scale (CES-D) at about gestational week 32 and again around 3 months following delivery. Postnatal depressiveness as defined by a CES-D score of at least 10 points was present in 10.3% of the mothers. After adjusting for prenatal depressiveness and other potential confounders, the investigators found that tiredness during the day, poor general sleep quality, getting less than 6 hours of sleep, taking longer than 20 minutes to fall asleep, and sleep loss of 2 hours or more per night during pregnancy were each associated with clinically significant postnatal depressive symptoms, with odds ratios of 1.87-2.19.

The full details of the study have been published (Arch Womens Ment Health. 2019 Jun;22[3]:327-37).

The impetus for this study of sleep problems in pregnancy as a predictor of postnatal depressive symptoms was a body of evidence linking insomnia to depression in both men and women. But it turns out that insomnia is a significant predictor of later onset of a wide variety of psychiatric disorders, not only depression, as highlighted in a recent systematic review and meta-analysis conducted by an international team of investigators, Dr. Paunio observed.

Baseline insomnia symptoms were associated with a 183% increased risk of later onset of depression, a 223% increased risk of anxiety, a 35%greater risk of alcohol abuse, and a 28% increased risk of psychosis. However, the insomnia/psychosis link must be viewed as tentative, as it was examined in only a single published study. The investigators rated the overall risk of bias in the studies included in their meta-analysis as moderate (Sleep Med Rev. 2019 Feb;43:96-105).

For Dr. Paunio, these findings suggest that interventional studies of early and effective treatment of insomnia as a potential means of preventing psychiatric disorders are in order.

She reported receiving research funding from the Academy of Finland, the Gyllenberg Foundation, and Finska Lakaresallskapet.

[email protected]

COPENHAGEN – Sleep problems during pregnancy are a risk factor for subsequent clinically significant postnatal depressive symptoms, Tiina Paunio, MD, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

“I think it is very important to understand that we need to screen pregnant women for sleep problems, even those without a history of depression, so we can have early treatment of insomnia – and also depression – because postnatal maternal depression is very much a risk for the child during a vulnerable period for development,” said Dr. Paunio, professor of psychiatry at the University of Helsinki.

She was a coinvestigator in a prospective study of the Finnish CHILD-SLEEP longitudinal birth cohort in which 1,398 women completed the Basic Nordic Sleep Questionnaire and the 10-item version of the Center for Epidemiological Studies Depression Scale (CES-D) at about gestational week 32 and again around 3 months following delivery. Postnatal depressiveness as defined by a CES-D score of at least 10 points was present in 10.3% of the mothers. After adjusting for prenatal depressiveness and other potential confounders, the investigators found that tiredness during the day, poor general sleep quality, getting less than 6 hours of sleep, taking longer than 20 minutes to fall asleep, and sleep loss of 2 hours or more per night during pregnancy were each associated with clinically significant postnatal depressive symptoms, with odds ratios of 1.87-2.19.

The full details of the study have been published (Arch Womens Ment Health. 2019 Jun;22[3]:327-37).

The impetus for this study of sleep problems in pregnancy as a predictor of postnatal depressive symptoms was a body of evidence linking insomnia to depression in both men and women. But it turns out that insomnia is a significant predictor of later onset of a wide variety of psychiatric disorders, not only depression, as highlighted in a recent systematic review and meta-analysis conducted by an international team of investigators, Dr. Paunio observed.

Baseline insomnia symptoms were associated with a 183% increased risk of later onset of depression, a 223% increased risk of anxiety, a 35%greater risk of alcohol abuse, and a 28% increased risk of psychosis. However, the insomnia/psychosis link must be viewed as tentative, as it was examined in only a single published study. The investigators rated the overall risk of bias in the studies included in their meta-analysis as moderate (Sleep Med Rev. 2019 Feb;43:96-105).

For Dr. Paunio, these findings suggest that interventional studies of early and effective treatment of insomnia as a potential means of preventing psychiatric disorders are in order.

She reported receiving research funding from the Academy of Finland, the Gyllenberg Foundation, and Finska Lakaresallskapet.

[email protected]

MADRID – The interleukin-17A inhibitor ixekizumab met all primary and secondary endpoints in a phase 3 trial in 6- to 18-year-olds with moderate to severe plaque psoriasis, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The results bode well for an underserved population.

“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.

At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.

The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.

The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.

An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.

The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.

More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.

And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.

“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.

He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.

Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.

Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.

[email protected]

SOURCE: Papp KA. EADV Late breaker.

MADRID – The interleukin-17A inhibitor ixekizumab met all primary and secondary endpoints in a phase 3 trial in 6- to 18-year-olds with moderate to severe plaque psoriasis, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The results bode well for an underserved population.

“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.

At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.

The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.

The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.

An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.

The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.

More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.

And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.

“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.

He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.

Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.

Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.

[email protected]

SOURCE: Papp KA. EADV Late breaker.

MADRID – The interleukin-17A inhibitor ixekizumab met all primary and secondary endpoints in a phase 3 trial in 6- to 18-year-olds with moderate to severe plaque psoriasis, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

The results bode well for an underserved population.

“I think all of us know that there is still a vulnerable population that remains a high-risk population because of the limited number of therapies available for them, and that is children,” said Dr. Papp, a dermatologist and president of Probity Medical Research, Inc., of Waterloo, Ont.

At present, etanercept, one of the earliest biologics to become available, and a relatively less effective one, is the only biologic approved for treatment of pediatric psoriasis. However, Lilly, which sponsored the phase 3 ixekizumab study, has announced that based upon the highly positive findings the company plans to seek Food and Drug Administration approval for an expanded indication for the medication in pediatric psoriasis. The company now markets ixekizumab for the approved indications of treatment of adults with moderate to severe plaque psoriasis, active psoriatic arthritis, or active ankylosing spondylitis.

The 12-week, double-blind, multicenter phase 3 trial known as IXORA-PEDS included 115 pediatric psoriasis patients randomized to weight-based ixekizumab, 30 on weight-based etanercept, and 58 on placebo. At the 12-week mark, everyone was switched to open-label ixekizumab in a long-term extension study. Children weighing less than 25 kg received a 40-mg loading dose of ixekizumab, followed by a maintenance dose of 20 mg by subcutaneous injection every 4 weeks. Patients weighing 25-50 kg got a starting dose of 80 mg, then 40 mg for maintenance therapy. Those who weighed more than 50 kg got the usual adult dosing: a 160-mg loading dose followed by 80 mg every 4 weeks. Etanercept was dosed at 0.8 mg/kg once weekly.

The coprimary endpoints were the proportion of subjects achieving a static Physician’s Global Assessment (sPGA) of 0 or 1 – that is, clear or almost clear skin – at week 12, and the PASI 75 response rate.

An sPGA of 0 or 1 at week 12 was documented in 81% of the ixekizumab group, 11% on placebo, and 40% of etanercept-treated patients, who on average had more severe baseline disease than did the other two groups.

The PASI 75 rate was 89% with ixekizumab, 25% for placebo, and 63% on etanercept. But Dr. Papp indicated that’s too low a bar. “I don’t think PASI 75s are the standard any longer,” he said.

More revealing was the PASI 90 rate: 78% with the IL-17A inhibitor, 5% in placebo-treated controls, and 40% with etanercept.

And then there’s the PASI 100 response rate: 50% with ixekizumab, 2% for placebo, and 17% for etanercept.

“I think this is very telling. I’ll leave it as a tantalizing comment that if one looks at the slope of the curve, it doesn’t yet seem to have reached its plateau at week 12 – and this is very similar to the pattern that we see in the adult population. I don’t have the long-term extension efficacy data, but I am, like you, very interested in seeing where this PASI 100 response rate finally plateaus,” Dr. Papp said.

He did, however, have the combined safety data for the 12-week double-blind phase plus the open-label extension, which he described as essentially the same as the adult experience. Injection-site reactions occurred in 19% of pediatric patients on ixekizumab, but they were generally mild and there were few if any treatment discontinuations for that reason. There was a 2% incidence of Crohn’s disease. Candidiasis and other infections were rare.

Seventy-one percent of the ixekizumab group had at least a 4-point improvement in itch on a 10-point self-rated scale by week 12, as did 20% of placebo-treated controls. A Dermatologic Life Quality Index score of 0 or 1 at week 12, indicative of no or minimal impact of psoriasis on quality of life, was documented in 64% of the ixekizumab group and 23% of controls.

Dr. Papp reported serving as a consultant, investigator, and/or speaker for Lilly and more than three dozen other pharmaceutical companies.

[email protected]

SOURCE: Papp KA. EADV Late breaker.

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

[email protected]

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

[email protected]

MADRID – Serlopitant, an investigational once-daily oral neurokinin-1 receptor antagonist, resulted in clinically meaningful improvement in psoriatic itch in a phase 2, double-blind, placebo-controlled randomized trial, David M. Pariser, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

The drug is not an effective stand alone treatment for psoriasis, though.

“The psoriasis itself did not improve during the trial. It’s the itch that improved. This drug is not designed for psoriasis; it’s going to be used for itching. If this does materialize as a treatment for psoriasis, it would be as an adjunct,” according to Dr. Pariser, a dermatologist at the Eastern Virginia School of Medicine, Norfolk.

Still, serlopitant addresses an unmet need for better treatment options for psoriatic itch. Up to 90% of psoriasis patients report experiencing pruritus, regardless of their disease severity.

“Although patients consider pruritus one of the most important, severe, and troublesome symptoms of psoriasis, clinicians have not historically recognized itch as a significant symptom, and treatments for psoriasis often don’t alleviate the associated pruritus,” he said.

Serlopitant has already shown efficacy and good tolerability in phase 2 studies in patients with prurigo nodularis and chronic pruritus.

The 8-week psoriatic itch trial included 204 adults with plaque psoriasis randomized to 5 mg of serlopitant once daily or placebo. Patients averaged 4.3% involved body surface area, and nearly two-thirds of them had moderate psoriasis by physician global assessment. The majority of patients rated their itch as severe; The average baseline score on the 0-10 Worst Itch Numeric Rating Scale was 8.2.

The primary study endpoint was achievement of at least a 4-point improvement on the Worst Itch Numeric Rating Scale. This was achieved in 33.9% of the serlopitant group and 21.1% of placebo-treated controls. The therapeutic benefit was consistent regardless of baseline body weight, gender, age, or extent of psoriasis-involved body surface area.

The safety data were consistent with what was seen in prior phase 2 studies for other dermatologic disorders. There were no serious adverse events, and the type and frequency of adverse events deemed related to treatment was similar in the two study arms.

“These results support the ongoing development of serlopitant across the spectrum of psoriatic disease,” Dr. Pariser declared.

The study was funded by Menlo Therapeutics. Dr. Pariser reported receiving research funding from and/or serving as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

[email protected]

PARIS – The first-ever randomized trial of in-hospital initiation of a PCSK9 inhibitor on top of guideline-recommended high-intensity statin therapy in the very-high-risk acute phase of an acute coronary syndrome (ACS) safely resulted in dramatically lower LDL cholesterol levels than with early prescribing of a high-intensity statin alone, Konstantinos C. Koskinas, MD, reported at the annual congress of the European Society of Cardiology.

At 8 weeks of follow-up, 90% of the dual-therapy group had achieved the new ESC guideline-recommended target of an LDL cholesterol less than 55 mg/dL, compared with 11% of patients randomized to high-intensity atorvastatin at 40 mg/day plus placebo injections. Moreover, 96% of patients on atorvastatin 40 mg/day plus evolocumab at 420 mg per subcutaneous injection were below the former target of an LDL cholesterol less than 70 mg/dL, as were 38% of those on the high-intensity statin alone, according to Dr. Koskinas, a cardiologist at the University of Bern (Switzerland).

The seven-center Swiss EVOPACS trial, featuring 308 ACS patients, could be considered a proof-of-concept study, as it lacked the size and duration to be powered to assess clinical outcomes.

“The clinical impact of very early LDL lowering with evolocumab initiated in the acute setting of ACS warrants further investigation in a dedicated cardiovascular outcomes trial,” Dr. Koskinas asserted. “We see this as the natural next step. Discussions are underway about a long-term trial with clinical endpoints, but no decisions have been made.”

The rationale for the EVOPACS trial is based upon current standard practice in ACS management, which includes initiation of a high-intensity statin during the acute phase of ACS, a particularly high-risk period for recurrent events. This practice has a Class IA recommendation in the guidelines based on published evidence that it results in a significantly reduced rate of the composite of death, MI, or rehospitalization for ACS within 30 days, compared with a less aggressive approach to LDL cholesterol lowering.

Yet even though the PCSK9 inhibitors are the 800-lb gorillas of LDL cholesterol lowering, they’ve never been tested in the setting of acute-phase ACS. For example, in the landmark ODYSSEY OUTCOMES trial, alirocumab was initiated on average 2.6 months after ACS, while in FOURIER the lag time between ACS and the start of evolocumab was 3.4 years, the cardiologist noted.

In contrast, all of the 37% of EVOPACS participants with an ST-segment elevation MI were enrolled in the study and on treatment within 24 hours after symptom onset. So were more than one-third of those with non–ST-elevation ACS, with the remainder getting onboard 24-72 hours after symptom onset.

The safety and tolerability of dual LDL cholesterol–lowering therapy were excellent in the brief EVOPACS study. There were no significant between-group differences in adverse events or serious adverse events, nor in prespecified events of special interest, including muscle pain, neurocognitive changes, or elevated liver enzyme levels.

The LDL cholesterol lowering achieved with dual therapy in EVOPACS was jaw dropping: Over the course of 8 weeks, the mean LDL cholesterol went from 132 to 31 mg/dL. In patients on early high-intensity atorvastatin alone, LDL cholesterol went from 139 to 80 mg/dL.

The full details of the EVOPACS trial have been published (J Am Coll Cardiol. 2019 Aug 16. doi: 10.1016/j.jacc.2019.08.010.

The trial was funded by Amgen. Dr. Koskinas reported receiving honoraria from Amgen and Sanofi.

[email protected]

PARIS – The first-ever randomized trial of in-hospital initiation of a PCSK9 inhibitor on top of guideline-recommended high-intensity statin therapy in the very-high-risk acute phase of an acute coronary syndrome (ACS) safely resulted in dramatically lower LDL cholesterol levels than with early prescribing of a high-intensity statin alone, Konstantinos C. Koskinas, MD, reported at the annual congress of the European Society of Cardiology.

At 8 weeks of follow-up, 90% of the dual-therapy group had achieved the new ESC guideline-recommended target of an LDL cholesterol less than 55 mg/dL, compared with 11% of patients randomized to high-intensity atorvastatin at 40 mg/day plus placebo injections. Moreover, 96% of patients on atorvastatin 40 mg/day plus evolocumab at 420 mg per subcutaneous injection were below the former target of an LDL cholesterol less than 70 mg/dL, as were 38% of those on the high-intensity statin alone, according to Dr. Koskinas, a cardiologist at the University of Bern (Switzerland).

The seven-center Swiss EVOPACS trial, featuring 308 ACS patients, could be considered a proof-of-concept study, as it lacked the size and duration to be powered to assess clinical outcomes.

“The clinical impact of very early LDL lowering with evolocumab initiated in the acute setting of ACS warrants further investigation in a dedicated cardiovascular outcomes trial,” Dr. Koskinas asserted. “We see this as the natural next step. Discussions are underway about a long-term trial with clinical endpoints, but no decisions have been made.”

The rationale for the EVOPACS trial is based upon current standard practice in ACS management, which includes initiation of a high-intensity statin during the acute phase of ACS, a particularly high-risk period for recurrent events. This practice has a Class IA recommendation in the guidelines based on published evidence that it results in a significantly reduced rate of the composite of death, MI, or rehospitalization for ACS within 30 days, compared with a less aggressive approach to LDL cholesterol lowering.

Yet even though the PCSK9 inhibitors are the 800-lb gorillas of LDL cholesterol lowering, they’ve never been tested in the setting of acute-phase ACS. For example, in the landmark ODYSSEY OUTCOMES trial, alirocumab was initiated on average 2.6 months after ACS, while in FOURIER the lag time between ACS and the start of evolocumab was 3.4 years, the cardiologist noted.

In contrast, all of the 37% of EVOPACS participants with an ST-segment elevation MI were enrolled in the study and on treatment within 24 hours after symptom onset. So were more than one-third of those with non–ST-elevation ACS, with the remainder getting onboard 24-72 hours after symptom onset.

The safety and tolerability of dual LDL cholesterol–lowering therapy were excellent in the brief EVOPACS study. There were no significant between-group differences in adverse events or serious adverse events, nor in prespecified events of special interest, including muscle pain, neurocognitive changes, or elevated liver enzyme levels.

The LDL cholesterol lowering achieved with dual therapy in EVOPACS was jaw dropping: Over the course of 8 weeks, the mean LDL cholesterol went from 132 to 31 mg/dL. In patients on early high-intensity atorvastatin alone, LDL cholesterol went from 139 to 80 mg/dL.

The full details of the EVOPACS trial have been published (J Am Coll Cardiol. 2019 Aug 16. doi: 10.1016/j.jacc.2019.08.010.

The trial was funded by Amgen. Dr. Koskinas reported receiving honoraria from Amgen and Sanofi.

[email protected]

PARIS – The first-ever randomized trial of in-hospital initiation of a PCSK9 inhibitor on top of guideline-recommended high-intensity statin therapy in the very-high-risk acute phase of an acute coronary syndrome (ACS) safely resulted in dramatically lower LDL cholesterol levels than with early prescribing of a high-intensity statin alone, Konstantinos C. Koskinas, MD, reported at the annual congress of the European Society of Cardiology.

At 8 weeks of follow-up, 90% of the dual-therapy group had achieved the new ESC guideline-recommended target of an LDL cholesterol less than 55 mg/dL, compared with 11% of patients randomized to high-intensity atorvastatin at 40 mg/day plus placebo injections. Moreover, 96% of patients on atorvastatin 40 mg/day plus evolocumab at 420 mg per subcutaneous injection were below the former target of an LDL cholesterol less than 70 mg/dL, as were 38% of those on the high-intensity statin alone, according to Dr. Koskinas, a cardiologist at the University of Bern (Switzerland).

The seven-center Swiss EVOPACS trial, featuring 308 ACS patients, could be considered a proof-of-concept study, as it lacked the size and duration to be powered to assess clinical outcomes.

“The clinical impact of very early LDL lowering with evolocumab initiated in the acute setting of ACS warrants further investigation in a dedicated cardiovascular outcomes trial,” Dr. Koskinas asserted. “We see this as the natural next step. Discussions are underway about a long-term trial with clinical endpoints, but no decisions have been made.”

The rationale for the EVOPACS trial is based upon current standard practice in ACS management, which includes initiation of a high-intensity statin during the acute phase of ACS, a particularly high-risk period for recurrent events. This practice has a Class IA recommendation in the guidelines based on published evidence that it results in a significantly reduced rate of the composite of death, MI, or rehospitalization for ACS within 30 days, compared with a less aggressive approach to LDL cholesterol lowering.

Yet even though the PCSK9 inhibitors are the 800-lb gorillas of LDL cholesterol lowering, they’ve never been tested in the setting of acute-phase ACS. For example, in the landmark ODYSSEY OUTCOMES trial, alirocumab was initiated on average 2.6 months after ACS, while in FOURIER the lag time between ACS and the start of evolocumab was 3.4 years, the cardiologist noted.

In contrast, all of the 37% of EVOPACS participants with an ST-segment elevation MI were enrolled in the study and on treatment within 24 hours after symptom onset. So were more than one-third of those with non–ST-elevation ACS, with the remainder getting onboard 24-72 hours after symptom onset.

The safety and tolerability of dual LDL cholesterol–lowering therapy were excellent in the brief EVOPACS study. There were no significant between-group differences in adverse events or serious adverse events, nor in prespecified events of special interest, including muscle pain, neurocognitive changes, or elevated liver enzyme levels.

The LDL cholesterol lowering achieved with dual therapy in EVOPACS was jaw dropping: Over the course of 8 weeks, the mean LDL cholesterol went from 132 to 31 mg/dL. In patients on early high-intensity atorvastatin alone, LDL cholesterol went from 139 to 80 mg/dL.

The full details of the EVOPACS trial have been published (J Am Coll Cardiol. 2019 Aug 16. doi: 10.1016/j.jacc.2019.08.010.

The trial was funded by Amgen. Dr. Koskinas reported receiving honoraria from Amgen and Sanofi.

[email protected]

STOCKHOLM – Early adolescence may be a period of heightened susceptibility to future development of multiple sclerosis (MS) resulting from exposure to pneumonia and other forms of lung inflammation, Scott Montgomery, PhD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

This is speculative, he readily acknowledged, but it is a hypothesis supported by multiple lines of evidence provided by separate Swedish national health care registry studies he has led that showed associations between pneumonia or infectious mononucleosis occurring in early adolescence and increased risk of later MS.

These findings are consistent with the well-established observations that two other causes of lung irritation – cigarette smoking and exposure to organic solvents – are also linked to increased risk of MS (Neurology. 2018 Jul 31;91[5]:e455-62), noted Dr. Montgomery, head of the clinical epidemiology research group at Örebro (Sweden) University.

Moreover, he and his coinvestigators also found in yet another Swedish national registry cohort study that one concussion during adolescence was independently associated with a statistically significant 1.22-fold increased risk of later MS, while two or more were linked to a 2.33-fold increased risk. In contrast, concussions occurring before age 11 years were not associated with any increased risk of MS, which suggests an age-defined period of susceptibility (Ann Neurol. 2017 Oct;82[4]:554-61).

“There seems to be greater brain resilience in childhood as compared to adolescence,” Dr. Montgomery commented.

The new Swedish registry pneumonia study included 6,109 Swedish MS patients and 49,479 controls matched for age, gender, and locale. In an analysis adjusted for education level and history of infectious mononucleosis, history of having pneumonia at age 11-15 years was independently associated with a 2.8-fold increased risk of subsequent MS. Pneumonia occurring at age 16-20 years was associated with a more modest 1.38-fold increased risk, which did not achieve statistical significance, while pneumonia up to age 5 years or at age 6-10 years conferred no increased risk. The investigators restricted their analysis to cases of pneumonia occurring up to age 20 years because that is younger than the typical age of MS onset. The age restriction sidestepped the potential for confounding by reverse causation since it is known that pneumonia occurs with increased frequency in patients with MS.

Because MS patients also have an increased risk of urinary tract infections, Dr. Montgomery and coinvestigators also analyzed the same pediatric data set for UTI rates broken down by 5-year age groups. Rates were similar in individuals who later developed MS and in controls, which suggests that the observed increase in MS risk associated with pneumonia in early adolescence was not an expression of an MS prodromal illness, he explained.

The investigators focused on pneumonia in childhood and adolescence as a potential trigger for MS because pneumonia results in more profound and prolonged inflammation than do other common respiratory illnesses. For example, pneumonia has been shown to be linked to increased risks of cardiovascular disease and chronic kidney disease for up to 5 years after the infection.

Developmentally, age 11-15 years is a period defined by peripubertal reorganization and synaptogenesis, while synaptic pruning and axonal myelination are on the agenda at age 16-20 years, Dr. Montgomery observed.

The study of infectious mononucleosis as a potential risk factor for MS included 4,527 Swedish MS patients and 3.2 million controls, all born during 1970-2000 and followed until 2014. In this analysis, infectious mononucleosis occurring at age 11-15 years was associated with the greatest risk of subsequent MS, with an associated 3.47-fold greater risk of the neurologic disease versus that seen in patients who did not have infectious mononucleosis at age 11-15 years

“It does look like a causal association between Epstein-Barr virus infection and subsequent MS,” according to Dr. Montgomery.

He noted that a plausible mechanism by which lung inflammation could predispose future MS has been put forth by German investigators. Using an animal model, they demonstrated that autoreactive T cells are prepared in bronchus-associated lymphoid tissue and attain a migratory profile allowing them to cross the blood-brain barrier and induce CNS autoimmune disease (Nature. 2012 Aug 30;488[7413]:675-9).

All of this, as Dr. Montgomery emphasized, is speculative at this point in regard to MS pathogenesis. What is not speculative, he continued, is the solid evidence that infection-related mortality after diagnosis of MS has gone down substantially in the current era of newer disease-modifying treatments, as he and his coinvestigators have demonstrated (Neurology. 2017 Aug 8;89[6]:555-62).

“People with MS, compared to the general population, are still at increased risk, but not nearly as much as the infection-related mortality risk present back in the 1960s-80s. So things have improved somewhat,” Dr. Montgomery said.

Which MS patients are at increased risk for mortality caused by infection? His Swedish national registry research demonstrates that the risk is essentially confined to patients with secondary or primary progressive MS or an Expanded Disability Status Scale score of 6 or more.

Another new study he presented at the meeting focused on the types of infections that are more common in a contemporary MS population than in MS-free individuals. This Swedish national cohort study included 6,602 patients diagnosed with MS during 2008-2016 and 61,828 age-, sex-, and location-matched controls. Infections serious enough to have resulted in hospitalization occurred 2.59 times more frequently in the MS population. The risk of meningitis and encephalitis was increased 6.16-fold, opportunistic infections were 2.72-fold more frequent, the risk of urinary tract and kidney infections was increased 2.44-fold, herpes virus infections were increased 2.32-fold, and the combined rate of pneumonia and influenza was roughly double that seen in the matched general population.

Dr. Montgomery reported receiving research funding from F. Hoffmann–La Roche, Novartis, and AstraZeneca and serving on an advisory board for IQVIA.
 

[email protected]

SOURCE: Montgomery S. ECTRIMS 2019, Abstract 270.
 

STOCKHOLM – Early adolescence may be a period of heightened susceptibility to future development of multiple sclerosis (MS) resulting from exposure to pneumonia and other forms of lung inflammation, Scott Montgomery, PhD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

This is speculative, he readily acknowledged, but it is a hypothesis supported by multiple lines of evidence provided by separate Swedish national health care registry studies he has led that showed associations between pneumonia or infectious mononucleosis occurring in early adolescence and increased risk of later MS.

These findings are consistent with the well-established observations that two other causes of lung irritation – cigarette smoking and exposure to organic solvents – are also linked to increased risk of MS (Neurology. 2018 Jul 31;91[5]:e455-62), noted Dr. Montgomery, head of the clinical epidemiology research group at Örebro (Sweden) University.

Moreover, he and his coinvestigators also found in yet another Swedish national registry cohort study that one concussion during adolescence was independently associated with a statistically significant 1.22-fold increased risk of later MS, while two or more were linked to a 2.33-fold increased risk. In contrast, concussions occurring before age 11 years were not associated with any increased risk of MS, which suggests an age-defined period of susceptibility (Ann Neurol. 2017 Oct;82[4]:554-61).

“There seems to be greater brain resilience in childhood as compared to adolescence,” Dr. Montgomery commented.

The new Swedish registry pneumonia study included 6,109 Swedish MS patients and 49,479 controls matched for age, gender, and locale. In an analysis adjusted for education level and history of infectious mononucleosis, history of having pneumonia at age 11-15 years was independently associated with a 2.8-fold increased risk of subsequent MS. Pneumonia occurring at age 16-20 years was associated with a more modest 1.38-fold increased risk, which did not achieve statistical significance, while pneumonia up to age 5 years or at age 6-10 years conferred no increased risk. The investigators restricted their analysis to cases of pneumonia occurring up to age 20 years because that is younger than the typical age of MS onset. The age restriction sidestepped the potential for confounding by reverse causation since it is known that pneumonia occurs with increased frequency in patients with MS.

Because MS patients also have an increased risk of urinary tract infections, Dr. Montgomery and coinvestigators also analyzed the same pediatric data set for UTI rates broken down by 5-year age groups. Rates were similar in individuals who later developed MS and in controls, which suggests that the observed increase in MS risk associated with pneumonia in early adolescence was not an expression of an MS prodromal illness, he explained.

The investigators focused on pneumonia in childhood and adolescence as a potential trigger for MS because pneumonia results in more profound and prolonged inflammation than do other common respiratory illnesses. For example, pneumonia has been shown to be linked to increased risks of cardiovascular disease and chronic kidney disease for up to 5 years after the infection.

Developmentally, age 11-15 years is a period defined by peripubertal reorganization and synaptogenesis, while synaptic pruning and axonal myelination are on the agenda at age 16-20 years, Dr. Montgomery observed.

The study of infectious mononucleosis as a potential risk factor for MS included 4,527 Swedish MS patients and 3.2 million controls, all born during 1970-2000 and followed until 2014. In this analysis, infectious mononucleosis occurring at age 11-15 years was associated with the greatest risk of subsequent MS, with an associated 3.47-fold greater risk of the neurologic disease versus that seen in patients who did not have infectious mononucleosis at age 11-15 years

“It does look like a causal association between Epstein-Barr virus infection and subsequent MS,” according to Dr. Montgomery.

He noted that a plausible mechanism by which lung inflammation could predispose future MS has been put forth by German investigators. Using an animal model, they demonstrated that autoreactive T cells are prepared in bronchus-associated lymphoid tissue and attain a migratory profile allowing them to cross the blood-brain barrier and induce CNS autoimmune disease (Nature. 2012 Aug 30;488[7413]:675-9).

All of this, as Dr. Montgomery emphasized, is speculative at this point in regard to MS pathogenesis. What is not speculative, he continued, is the solid evidence that infection-related mortality after diagnosis of MS has gone down substantially in the current era of newer disease-modifying treatments, as he and his coinvestigators have demonstrated (Neurology. 2017 Aug 8;89[6]:555-62).

“People with MS, compared to the general population, are still at increased risk, but not nearly as much as the infection-related mortality risk present back in the 1960s-80s. So things have improved somewhat,” Dr. Montgomery said.

Which MS patients are at increased risk for mortality caused by infection? His Swedish national registry research demonstrates that the risk is essentially confined to patients with secondary or primary progressive MS or an Expanded Disability Status Scale score of 6 or more.

Another new study he presented at the meeting focused on the types of infections that are more common in a contemporary MS population than in MS-free individuals. This Swedish national cohort study included 6,602 patients diagnosed with MS during 2008-2016 and 61,828 age-, sex-, and location-matched controls. Infections serious enough to have resulted in hospitalization occurred 2.59 times more frequently in the MS population. The risk of meningitis and encephalitis was increased 6.16-fold, opportunistic infections were 2.72-fold more frequent, the risk of urinary tract and kidney infections was increased 2.44-fold, herpes virus infections were increased 2.32-fold, and the combined rate of pneumonia and influenza was roughly double that seen in the matched general population.

Dr. Montgomery reported receiving research funding from F. Hoffmann–La Roche, Novartis, and AstraZeneca and serving on an advisory board for IQVIA.
 

[email protected]

SOURCE: Montgomery S. ECTRIMS 2019, Abstract 270.
 

STOCKHOLM – Early adolescence may be a period of heightened susceptibility to future development of multiple sclerosis (MS) resulting from exposure to pneumonia and other forms of lung inflammation, Scott Montgomery, PhD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

This is speculative, he readily acknowledged, but it is a hypothesis supported by multiple lines of evidence provided by separate Swedish national health care registry studies he has led that showed associations between pneumonia or infectious mononucleosis occurring in early adolescence and increased risk of later MS.

These findings are consistent with the well-established observations that two other causes of lung irritation – cigarette smoking and exposure to organic solvents – are also linked to increased risk of MS (Neurology. 2018 Jul 31;91[5]:e455-62), noted Dr. Montgomery, head of the clinical epidemiology research group at Örebro (Sweden) University.

Moreover, he and his coinvestigators also found in yet another Swedish national registry cohort study that one concussion during adolescence was independently associated with a statistically significant 1.22-fold increased risk of later MS, while two or more were linked to a 2.33-fold increased risk. In contrast, concussions occurring before age 11 years were not associated with any increased risk of MS, which suggests an age-defined period of susceptibility (Ann Neurol. 2017 Oct;82[4]:554-61).

“There seems to be greater brain resilience in childhood as compared to adolescence,” Dr. Montgomery commented.

The new Swedish registry pneumonia study included 6,109 Swedish MS patients and 49,479 controls matched for age, gender, and locale. In an analysis adjusted for education level and history of infectious mononucleosis, history of having pneumonia at age 11-15 years was independently associated with a 2.8-fold increased risk of subsequent MS. Pneumonia occurring at age 16-20 years was associated with a more modest 1.38-fold increased risk, which did not achieve statistical significance, while pneumonia up to age 5 years or at age 6-10 years conferred no increased risk. The investigators restricted their analysis to cases of pneumonia occurring up to age 20 years because that is younger than the typical age of MS onset. The age restriction sidestepped the potential for confounding by reverse causation since it is known that pneumonia occurs with increased frequency in patients with MS.

Because MS patients also have an increased risk of urinary tract infections, Dr. Montgomery and coinvestigators also analyzed the same pediatric data set for UTI rates broken down by 5-year age groups. Rates were similar in individuals who later developed MS and in controls, which suggests that the observed increase in MS risk associated with pneumonia in early adolescence was not an expression of an MS prodromal illness, he explained.

The investigators focused on pneumonia in childhood and adolescence as a potential trigger for MS because pneumonia results in more profound and prolonged inflammation than do other common respiratory illnesses. For example, pneumonia has been shown to be linked to increased risks of cardiovascular disease and chronic kidney disease for up to 5 years after the infection.

Developmentally, age 11-15 years is a period defined by peripubertal reorganization and synaptogenesis, while synaptic pruning and axonal myelination are on the agenda at age 16-20 years, Dr. Montgomery observed.

The study of infectious mononucleosis as a potential risk factor for MS included 4,527 Swedish MS patients and 3.2 million controls, all born during 1970-2000 and followed until 2014. In this analysis, infectious mononucleosis occurring at age 11-15 years was associated with the greatest risk of subsequent MS, with an associated 3.47-fold greater risk of the neurologic disease versus that seen in patients who did not have infectious mononucleosis at age 11-15 years

“It does look like a causal association between Epstein-Barr virus infection and subsequent MS,” according to Dr. Montgomery.

He noted that a plausible mechanism by which lung inflammation could predispose future MS has been put forth by German investigators. Using an animal model, they demonstrated that autoreactive T cells are prepared in bronchus-associated lymphoid tissue and attain a migratory profile allowing them to cross the blood-brain barrier and induce CNS autoimmune disease (Nature. 2012 Aug 30;488[7413]:675-9).

All of this, as Dr. Montgomery emphasized, is speculative at this point in regard to MS pathogenesis. What is not speculative, he continued, is the solid evidence that infection-related mortality after diagnosis of MS has gone down substantially in the current era of newer disease-modifying treatments, as he and his coinvestigators have demonstrated (Neurology. 2017 Aug 8;89[6]:555-62).

“People with MS, compared to the general population, are still at increased risk, but not nearly as much as the infection-related mortality risk present back in the 1960s-80s. So things have improved somewhat,” Dr. Montgomery said.

Which MS patients are at increased risk for mortality caused by infection? His Swedish national registry research demonstrates that the risk is essentially confined to patients with secondary or primary progressive MS or an Expanded Disability Status Scale score of 6 or more.

Another new study he presented at the meeting focused on the types of infections that are more common in a contemporary MS population than in MS-free individuals. This Swedish national cohort study included 6,602 patients diagnosed with MS during 2008-2016 and 61,828 age-, sex-, and location-matched controls. Infections serious enough to have resulted in hospitalization occurred 2.59 times more frequently in the MS population. The risk of meningitis and encephalitis was increased 6.16-fold, opportunistic infections were 2.72-fold more frequent, the risk of urinary tract and kidney infections was increased 2.44-fold, herpes virus infections were increased 2.32-fold, and the combined rate of pneumonia and influenza was roughly double that seen in the matched general population.

Dr. Montgomery reported receiving research funding from F. Hoffmann–La Roche, Novartis, and AstraZeneca and serving on an advisory board for IQVIA.
 

[email protected]

SOURCE: Montgomery S. ECTRIMS 2019, Abstract 270.
 

STOCKHOLM – Here’s another good reason for smokers with multiple sclerosis (MS) to quit the tobacco habit: Their cognitive function may get a boost as a result, Ebtesam Alshehri, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

“We found that smokers have reduced Processing Speed Test scores compared with nonsmokers. They also have more brain atrophy. And we found that former smokers had intermediate results between current smokers and never smokers, suggesting that there is a benefit of smoking cessation early in the course of the disease,” explained Dr. Alshehri, a clinical neuroimmunology fellow at the Cleveland Clinic.

Dr. Alshehri and colleagues presented a cross-sectional study of 997 patients with MS. At the Cleveland Clinic, patients with MS routinely undergo the Processing Speed Test (PST) – an electronic version of the Symbol Digit Modalities Test – at each clinical visit as a means of assessing cognitive function. All 997 patients also underwent quantitative brain MRI within 90 days of their cognitive function test. The study population consisted of 520 never smokers, 335 ex-smokers, and 142 current smokers. Seventy-seven percent of the patients had relapsing-remitting MS, and most of the rest had progressive disease.

The impetus for this hypothesis-generating study was a recognition that while smoking has previously been reported to be a risk factor for MS and has also been associated with accelerated progression of disability in patients who already have the disease, the impact of smoking on cognition and brain atrophy in the MS population has been a murky area, according to Dr. Alshehri.

In a multivariate analysis adjusted for age, disease duration, and disease course, smoking status was an independent predictor of PST score. Former smokers scored an average of 3.6 points lower than never smokers, and current smokers scored 5.9 points lower than the never smokers. Similarly, former smokers appeared better off than current smokers in terms of brain atrophy as measured by whole brain function on MRI: The ex-smokers had significantly greater brain atrophy than that of never smokers, an effect that was magnified in current smokers.

For Dr. Alshehri, these findings contain an important message for physicians: “I think as clinicians we should ask our patients with MS about tobacco use at each visit, remind patients about the risks of smoking and the negative impact not only on their general health, but also the impact on disease progression and disability worsening, encourage patients to stop smoking, and provide them with this encouraging data.”

She reported having no financial conflicts regarding this study, which was conducted free of commercial support.

[email protected]

SOURCE: Alshehri E et al. ECTRIMS 2019. Abstract P461.

STOCKHOLM – Here’s another good reason for smokers with multiple sclerosis (MS) to quit the tobacco habit: Their cognitive function may get a boost as a result, Ebtesam Alshehri, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

“We found that smokers have reduced Processing Speed Test scores compared with nonsmokers. They also have more brain atrophy. And we found that former smokers had intermediate results between current smokers and never smokers, suggesting that there is a benefit of smoking cessation early in the course of the disease,” explained Dr. Alshehri, a clinical neuroimmunology fellow at the Cleveland Clinic.

Dr. Alshehri and colleagues presented a cross-sectional study of 997 patients with MS. At the Cleveland Clinic, patients with MS routinely undergo the Processing Speed Test (PST) – an electronic version of the Symbol Digit Modalities Test – at each clinical visit as a means of assessing cognitive function. All 997 patients also underwent quantitative brain MRI within 90 days of their cognitive function test. The study population consisted of 520 never smokers, 335 ex-smokers, and 142 current smokers. Seventy-seven percent of the patients had relapsing-remitting MS, and most of the rest had progressive disease.

The impetus for this hypothesis-generating study was a recognition that while smoking has previously been reported to be a risk factor for MS and has also been associated with accelerated progression of disability in patients who already have the disease, the impact of smoking on cognition and brain atrophy in the MS population has been a murky area, according to Dr. Alshehri.

In a multivariate analysis adjusted for age, disease duration, and disease course, smoking status was an independent predictor of PST score. Former smokers scored an average of 3.6 points lower than never smokers, and current smokers scored 5.9 points lower than the never smokers. Similarly, former smokers appeared better off than current smokers in terms of brain atrophy as measured by whole brain function on MRI: The ex-smokers had significantly greater brain atrophy than that of never smokers, an effect that was magnified in current smokers.

For Dr. Alshehri, these findings contain an important message for physicians: “I think as clinicians we should ask our patients with MS about tobacco use at each visit, remind patients about the risks of smoking and the negative impact not only on their general health, but also the impact on disease progression and disability worsening, encourage patients to stop smoking, and provide them with this encouraging data.”

She reported having no financial conflicts regarding this study, which was conducted free of commercial support.

[email protected]

SOURCE: Alshehri E et al. ECTRIMS 2019. Abstract P461.

STOCKHOLM – Here’s another good reason for smokers with multiple sclerosis (MS) to quit the tobacco habit: Their cognitive function may get a boost as a result, Ebtesam Alshehri, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Bruce Jancin/MDedge News

“We found that smokers have reduced Processing Speed Test scores compared with nonsmokers. They also have more brain atrophy. And we found that former smokers had intermediate results between current smokers and never smokers, suggesting that there is a benefit of smoking cessation early in the course of the disease,” explained Dr. Alshehri, a clinical neuroimmunology fellow at the Cleveland Clinic.

Dr. Alshehri and colleagues presented a cross-sectional study of 997 patients with MS. At the Cleveland Clinic, patients with MS routinely undergo the Processing Speed Test (PST) – an electronic version of the Symbol Digit Modalities Test – at each clinical visit as a means of assessing cognitive function. All 997 patients also underwent quantitative brain MRI within 90 days of their cognitive function test. The study population consisted of 520 never smokers, 335 ex-smokers, and 142 current smokers. Seventy-seven percent of the patients had relapsing-remitting MS, and most of the rest had progressive disease.

The impetus for this hypothesis-generating study was a recognition that while smoking has previously been reported to be a risk factor for MS and has also been associated with accelerated progression of disability in patients who already have the disease, the impact of smoking on cognition and brain atrophy in the MS population has been a murky area, according to Dr. Alshehri.

In a multivariate analysis adjusted for age, disease duration, and disease course, smoking status was an independent predictor of PST score. Former smokers scored an average of 3.6 points lower than never smokers, and current smokers scored 5.9 points lower than the never smokers. Similarly, former smokers appeared better off than current smokers in terms of brain atrophy as measured by whole brain function on MRI: The ex-smokers had significantly greater brain atrophy than that of never smokers, an effect that was magnified in current smokers.

For Dr. Alshehri, these findings contain an important message for physicians: “I think as clinicians we should ask our patients with MS about tobacco use at each visit, remind patients about the risks of smoking and the negative impact not only on their general health, but also the impact on disease progression and disability worsening, encourage patients to stop smoking, and provide them with this encouraging data.”

She reported having no financial conflicts regarding this study, which was conducted free of commercial support.

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SOURCE: Alshehri E et al. ECTRIMS 2019. Abstract P461.