Two-year follow-up data from an international, multicenter, randomized trial of ixekizumab in pediatric patients with moderate to severe psoriasis demonstrate prolonged efficacy and no new safety signals with the interleukin (IL)-17 inhibitor, investigators reported.
In addition, findings of a substudy, which evaluated randomized withdrawal of treatment after 60 weeks, suggest patients were able to regain benefit after not being treated for a period.
Ixekizumab (Taltz) was approved by the US Food and Drug Administration for treating pediatric psoriasis in March 2020 for patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
The trial (IXORA-PEDS) involved 171 patients aged 6 to 17 years (mean age, 13.5 years; 99 females and 72 males), who were randomly assigned to receive ixekizumab via subcutaneous administration every 4 weeks (115) or placebo (56) for 12 weeks. Thereafter, 166 patients continued in an open-label maintenance period in which they were treated every 4 weeks for 12–60 weeks. This was followed by an extension period of up to 108 weeks, which was completed by 139 patients (83.7%). At baseline, the patients' Psoriasis Area and Severity Index (PASI) score was 12 or higher, the static Physician's Global Assessment (sPGA) score was 3 or higher, and 10% or more of body surface area was affected.
In the study, at 12 weeks, treatment with ixekizumab was superior to placebo, with sustained responses through 48 weeks. In the follow-up phase, primary and secondary endpoints were sustained through week 108, with patients achieving or maintaining PASI 75 (91.7%), PASI 90 (79%), PASI 100 (55.1%), sPGA 0 or 1 (78.3%), and sPGA 0 (52.4%). Significant improvements in itch were seen at 12 weeks and were sustained with "meaningful improvements in itch for 78.5% of these patients at week 108," the investigators report.
Among the patients who received ixekizumab, clearance rates in areas that are difficult to treat increased from week 12 to week 108 among those affected. During this time, clearance of nail psoriasis increased from 22.8% to 68.1%, clearance of palmoplantar psoriasis increased from 46.2% to 90%, clearance of scalp psoriasis increased from 70.7% to 76.2%, and clearance of genital psoriasis increased from 83.3% to 87.5%.
No new safety findings during weeks 48 to 108 of the trial were reported, including no new cases of inflammatory bowel disease (IBD) or Candida infections. The results were reported in JAMA Dermatology.
"Safety is really what we think of most when we are talking about pediatric patients, especially since they may be on these for decades and especially since they most commonly start these therapies in adolescence," said Amy Paller, MD, the study's lead author, in an interview. "To be able to take this out 108 weeks, 2 years, is starting to get to a point where we are getting more comfortable with safety. Clearly, no new signals arose." Paller is chair of the Department of Dermatology and professor of dermatology and pediatrics, Northwestern University, Chicago, Illinois.
One of the biggest concerns with using IL-17 inhibitors such as ixekizumab to manage psoriasis is the development of IBD, said Paller. She noted that four cases of IBD were reported before the extension phase of the trial but that no new IBD cases were reported after week 48.
"We would not start this as a treatment of choice in someone with Crohn's disease, or perhaps we would think twice about using it in someone with a strong family history [of Crohn's disease]," said Paller, who is also the director of the Skin Biology and Diseases Resource-Based Center at Northwestern. "Otherwise, it does not make me concerned about its use."
Commenting on the study, Kelly M. Cordoro, MD, professor of dermatology and pediatrics at the University of California, San Francisco, said that the trial's results provide additional evidence regarding the optimal management of pediatric psoriasis.
"The landscape has shifted toward involving more pediatric patients in clinical trials, thereby providing dermatologists with data to select safe and effective therapies to manage children with psoriasis," Cordoro said in an interview. "We have data showing that children with psoriasis have been undertreated, likely because of concerns about safety. The more evidence available from trials such as this, the more likely children are to receive necessary treatment."
The efficacy data from the study on difficult-to-treat areas of psoriasis, in addition to improvements in BSA and PASI measures, are significant for clinicians deciding on a therapy for patients with psoriasis concentrated in specific body sites. "It was very valuable that the efficacy data was provided by site, such as scalp, palmoplantar, nails, and genital psoriasis, as these are low-BSA but high-impact areas for patients," said Cordoro.
The trial data on Crohn's disease buttress her decision to continue to refrain from initiating ixekizumab in a child with IBD or who is at high risk for IBD. "I was happy to see that there was not a signal for Candida infection," she added.
Interestingly, in the substudy in the European population, in which there was a double-blind, randomized withdrawal period, fewer patients who were reassigned to receive ixekizumab experienced relapsed in comparison to those who were reassigned to receive placebo. A total of 90.9% of patients who received placebo experienced relapse, compared with 17.6% of patients treated with ixekizumab. The median time to relapse in the placebo group was 149 days.
"There are data in the adult population that suggest intermittent treatment does allow for recapture of clinical response," said Cordoro. "While it is not a large enough dataset to know definitively, this substudy of patients suggests the possibility of intermittent treatment and the ability to regain control [of psoriasis] after a period off drug."
The study was funded by Eli Lilly. Paller is an investigator and consultant for Eli Lilly. Several other authors have received grants, personal fees, and/or were a consultant to Eli Lilly, and two authors are Eli Lilly employees. Cordoro reported no relevant financial relationships.
JAMA Dermatol. Published online April 13, 2022. Full text
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Image 1: Northwestern University, Chicago
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Cite this: Louise Gagnon. Long-term Efficacy, Safety Data for Ixekizumab in Pediatric Psoriasis Reported - Medscape - Apr 25, 2022.