PEER Registry

The Pediatric Eczema Elective Registry (PEER) is a long-term, nationwide US observational cohort set up in 2004 as a post-marketing requirement after Pimecrolimus approval. It enrols children aged 2–17 with Atopic Dermatitis who have used pimecrolimus for at least 42 of the previous 180 days. Children then report their skin status and treatments every 6 months. It is the largest paediatric safety dataset for Topical Calcineurin Inhibitors. The study team is at the University of Pennsylvania, and the 2015 paper has a co-author from the drug’s then-owner (Valeant). Under-2s are not enrolled, so it does not directly cover the youngest toddlers.

PEER Registry [part-of] Pimecrolimus FDA [regulates] PEER Registry PEER Registry [relates] Atopic Dermatitis

Malignancy results (Margolis et al., JAMA Dermatol 2015). By May 2014, 7,457 children had contributed 26,792 person-years, with a mean pimecrolimus use of 793 g each. Five cancers were reported: 2 leukaemias, 1 osteosarcoma and 2 lymphomas. There were no skin cancers. Compared with age-standardised US SEER rates, the standardised incidence ratio for all cancers was 1.2 (95% CI 0.5–2.8). It was 2.9 (0.7–11.7) for lymphoma and 2.0 (0.5–8.2) for leukaemia, and none was statistically significant. The authors concluded that an increased cancer risk from pimecrolimus “as it was used in the PEER cohort” seems unlikely. This is the main paediatric dataset cited against the 2006 FDA boxed warning. The lymphoma confidence interval is wide, because the numbers are small.

PEER Registry [contradicts] FDA PEER Registry [supports] Topical Calcineurin Inhibitors PEER Registry [supports] Pimecrolimus

Persistence findings (Margolis et al., JAMA Dermatol 2014). The same registry (7,157 children, 22,550 person-years at that analysis) found that over 80% of participants at every age from 2 to 26 still had eczema symptoms or were using treatment. Only by age 20 had half had at least one 6-month symptom- and treatment-free period. The authors suggested AD is “probably a life-long illness.” Population cohorts such as ALSPAC paint a more optimistic picture. PEER children all needed a second-line prescription cream, so they are likely a more persistent, more severe group than average.

PEER Registry [relates] Eczema Prognosis PEER Registry [contradicts] ALSPAC

Conflict: [Margolis et al., JAMA Dermatol 2014, PEER] says >80% of children aged 2–26 still had symptoms or used treatment, and only half had a 6-month clear spell by age 20. [Paternoster et al., JACI 2018, ALSPAC] says the commonest eczema pattern is early-onset-early-resolving (13–15% of children), clearing by 6–7 years, with only 5–7% early-onset-persistent. Unresolved, and likely due to selection (a registry of pimecrolimus users vs a whole birth cohort). Add to open_questions.

Connections

• Topical Calcineurin Inhibitors — reassuring registry data vs boxed warning, source: Margolis JAMA Dermatol 2015
• Pimecrolimus — drug under surveillance, source: Margolis JAMA Dermatol 2015
• Eczema Prognosis — registry arm of the outgrow-it conflict, source: Margolis 2014
• FDA — registry was a post-marketing requirement; data contest boxed warning, source: Margolis 2015
• ALSPAC — contrasting population-cohort persistence estimates, source: Paternoster 2018; Margolis 2014
• Atopic Dermatitis — >80% symptomatic or treated at every age 2–26, source: Margolis 2014