In the Journals

Phase 2 trial supports weight-based Otezla dosing in pediatric patients with psoriasis

An improvement in Psoriasis Area and Severity Index scores occurred as early as week 2 in a phase 2 trial of adolescent patients with moderate to severe plaque psoriasis treated with Otezla 20 mg or 30 mg twice daily, leading researchers to support the use of weight-based dosing in children and adolescents, according to analysis in Journal of the American Academy of Dermatology.

“Our preliminary findings provide the first evidence of the potential efficacy of apremilast in pediatric patients with plaque psoriasis, and safety was generally consistent with the known safety profile of apremilast in adult patients with psoriasis,” Amy S. Paller, MD, Walter J. Hamlin Professor and chair of dermatology at Northwestern University Feinberg School of Medicine, and colleagues wrote.

The phase 2, multicenter, open-label study at 10 sites in the U.S., Canada and Europe enrolled pediatric patients into two groups to evaluate the pharmacokinetics and insight on the proper pediatric dosage for a phase 3 study.

Twenty-one patients in group 1 aged 12 to 17 years, weighing at least 35 kg to less than 70 kg, received Otezla (apremilast, Celgene Corp.) 20 mg, and those weighing at least 70 kg received apremilast 30 mg twice daily. Group 2 consisted of 21 patients aged 6 to 11 years and weighing at least 15 kg who were assigned apremilast 20 mg twice daily. The majority of patients were white (76.2%).

Patients received apremilast for 2 weeks and then underwent a 48-week extension treatment period and a posttreatment observation follow-up of up to 52 weeks.

Most patients (92.9%) were compliant with the study treatment.

All doses represent twice-daily administration throughout the study within both groups.

In the pharmacokinetics analysis, apremilast concentrations were lower in adolescents who received apremilast 20 mg twice daily compared with those on 30 mg twice daily and children who received apremilast 20 mg twice daily, according to researchers.

Apremilast concentrations were weight- and dose-dependent. Concentrations were mostly lower among those whose body weight was 50 kg to less than 70 kg who received apremilast 20 mg compared with those weighing at least 70 kg who received apremilast 30 mg and those weighing less than 50 kg who received 20 mg, according to the study. The maximal concentration of apremilast occurred at 2 to 3 hours post-dose.

Most patients experienced one or more mild to moderate treatment-emergent adverse events.

One patient in group 1 (apremilast 20 mg) had a severe headache and severe abdominal pain beginning on day 1 and each resolved the next day.

Nausea (52.4%), headache (45.2%), abdominal pain (42.9%), nasopharyngitis (38.1%), diarrhea (35.7%) and vomiting (31%) were the most frequently reported adverse events.

Group 1 experienced more nausea, nasopharyngitis and diarrhea, whereas group 2 had more headache, abdominal pain and vomiting. Weight loss was exhibited in both groups treated with 20 mg but resolved at study follow-up.

PASI score improvement was seen as early as week 2 in both treatment arms. At week 16, the mean percentage change from baseline in PASI score was –69.6 (standard deviation [SD], 19.5) for adolescents treated with apremilast 20 mg, –66.5 (SD, 17.1) for those treated with 30 mg and –79.3 (SD, 17.4) for children treated with apremilast 20 mg, according to researchers.

“Our exploratory efficacy findings lend further support to the use of weight-based dosing in pediatric patients. A planned phase 3 study will investigate the efficacy and safety of weight-based apremilast dosing for children and adolescents with moderate to severe plaque psoriasis,” Paller and colleagues wrote.

Although safety in this pediatric population was generally similar to reports in adults, there was a higher incidence of common adverse events.

The study limitations include a small sample size, a predominantly white study population and a lack of children weighing less than 20 kg.

Dose titration will be implemented in the upcoming phase 3, which may minimize adverse events, as doing so has in adult studies, according to the researchers. – by Abigail Sutton

 

Disclosures: The authors acknowledge support for this study from Celgene Corporation. Paller reports she received honoraria as a consultant for Asana, Dermira, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, UCB and Valeant. She also reports being an investigator for AbbVie, Celgene Corporation, Eli Lilly, Galderma, Janssen, LEO Pharma and Novartis. Please see the study for all other authors’ relevant financial disclosures.

An improvement in Psoriasis Area and Severity Index scores occurred as early as week 2 in a phase 2 trial of adolescent patients with moderate to severe plaque psoriasis treated with Otezla 20 mg or 30 mg twice daily, leading researchers to support the use of weight-based dosing in children and adolescents, according to analysis in Journal of the American Academy of Dermatology.

“Our preliminary findings provide the first evidence of the potential efficacy of apremilast in pediatric patients with plaque psoriasis, and safety was generally consistent with the known safety profile of apremilast in adult patients with psoriasis,” Amy S. Paller, MD, Walter J. Hamlin Professor and chair of dermatology at Northwestern University Feinberg School of Medicine, and colleagues wrote.

The phase 2, multicenter, open-label study at 10 sites in the U.S., Canada and Europe enrolled pediatric patients into two groups to evaluate the pharmacokinetics and insight on the proper pediatric dosage for a phase 3 study.

Twenty-one patients in group 1 aged 12 to 17 years, weighing at least 35 kg to less than 70 kg, received Otezla (apremilast, Celgene Corp.) 20 mg, and those weighing at least 70 kg received apremilast 30 mg twice daily. Group 2 consisted of 21 patients aged 6 to 11 years and weighing at least 15 kg who were assigned apremilast 20 mg twice daily. The majority of patients were white (76.2%).

Patients received apremilast for 2 weeks and then underwent a 48-week extension treatment period and a posttreatment observation follow-up of up to 52 weeks.

Most patients (92.9%) were compliant with the study treatment.

All doses represent twice-daily administration throughout the study within both groups.

In the pharmacokinetics analysis, apremilast concentrations were lower in adolescents who received apremilast 20 mg twice daily compared with those on 30 mg twice daily and children who received apremilast 20 mg twice daily, according to researchers.

Apremilast concentrations were weight- and dose-dependent. Concentrations were mostly lower among those whose body weight was 50 kg to less than 70 kg who received apremilast 20 mg compared with those weighing at least 70 kg who received apremilast 30 mg and those weighing less than 50 kg who received 20 mg, according to the study. The maximal concentration of apremilast occurred at 2 to 3 hours post-dose.

Most patients experienced one or more mild to moderate treatment-emergent adverse events.

One patient in group 1 (apremilast 20 mg) had a severe headache and severe abdominal pain beginning on day 1 and each resolved the next day.

Nausea (52.4%), headache (45.2%), abdominal pain (42.9%), nasopharyngitis (38.1%), diarrhea (35.7%) and vomiting (31%) were the most frequently reported adverse events.

Group 1 experienced more nausea, nasopharyngitis and diarrhea, whereas group 2 had more headache, abdominal pain and vomiting. Weight loss was exhibited in both groups treated with 20 mg but resolved at study follow-up.

PASI score improvement was seen as early as week 2 in both treatment arms. At week 16, the mean percentage change from baseline in PASI score was –69.6 (standard deviation [SD], 19.5) for adolescents treated with apremilast 20 mg, –66.5 (SD, 17.1) for those treated with 30 mg and –79.3 (SD, 17.4) for children treated with apremilast 20 mg, according to researchers.

“Our exploratory efficacy findings lend further support to the use of weight-based dosing in pediatric patients. A planned phase 3 study will investigate the efficacy and safety of weight-based apremilast dosing for children and adolescents with moderate to severe plaque psoriasis,” Paller and colleagues wrote.

Although safety in this pediatric population was generally similar to reports in adults, there was a higher incidence of common adverse events.

The study limitations include a small sample size, a predominantly white study population and a lack of children weighing less than 20 kg.

Dose titration will be implemented in the upcoming phase 3, which may minimize adverse events, as doing so has in adult studies, according to the researchers. – by Abigail Sutton

 

Disclosures: The authors acknowledge support for this study from Celgene Corporation. Paller reports she received honoraria as a consultant for Asana, Dermira, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, UCB and Valeant. She also reports being an investigator for AbbVie, Celgene Corporation, Eli Lilly, Galderma, Janssen, LEO Pharma and Novartis. Please see the study for all other authors’ relevant financial disclosures.