033 A novel, nonsteroidal, topical, anti-inflammatory, phosphodiesterase inhibitor, Crisaborole Topical Ointment, 2%, in two phase 3 studies in children and adults with mild to moderate atopic dermatitis

Abstract

Interventions often result in statistically significant quality of life (QoL) improvement, but may not reach the threshold of clinical importance. The minimal clinically important difference (MCID) is the minimal score change of relevance clinically. We introduce the concept of 2MCID, a score change at least twice the usual threshold (i.e. 8 for DLQI), highlighting therapies changing by this higher threshold. A systematic review was conducted of the use of QoL instruments and of the impact of psoriasis treatments in randomized controlled trials (RCTs). 388 search terms were used to conduct searches in six databases adhering to PRISMA guidelines. Two assessors independently reviewed abstracts: a third resolved differences. Of 3646 screened publications, 99 articles (100 trials) involving 33,215 subjects met inclusion eligibility criteria. Of these 100 trials, 37 reported MCID; 32 DLQI, 10 SF-36 and 6 EQ-5D. 33 trials tested topical therapy, 18 systemic, 39 biologics, 9 phototherapy and 10 other interventions. For studies with treatment endpoint or assessment at 12 weeks, the interventions with the greatest average DLQI impact in each category were: Liquor Carbonis Distillate 15% (>1MCID, 5.8 pts), ciclosporin 3-5 mg/kg (>1MCID, 6.6 pts), secukinumab 300 mg (>2MCID, 11.4 pts), PUVAsol 0.6 mg/kg + isotretinoin 0.5 mg/kg (>2MCID, 11.2 pts) and educational programme (1MCID, 4 pts). Clolobetasol spray 0.05% (8 points, 4 weeks), ustekinumab 90 mg (8, 12), etanercept 50 mg (8.7, 24) and MTX 15 mg (8.7, 16) also reached 2MCID. The concept of '2MCID' adds meaning to score change when comparing therapies and results across different QoL instruments, though this requires further validation. However secukinumab and PUVAsol + isotretinoin both reached 2MCID at 12 weeks, according well with clinical experience.

Perceptions on Management of Atopic Dermatitis in Children Under 2 Years by Community Pediatricians: A Focus Group Study

“…13-19 This is of concern as some treatments in these guidelines are indicated only for children 2 years and older, including pimecrolimus 1% cream (Elidel), and tacrolimus 0.03% and 0.1% ointment (Protopic). 10-12 PCPs also appear to treat AD differently in children under 2 years, likely due to heightened concern about TCS safety and tolerability in this age group. 20 All focus groups agreed that age-specific guidelines are warranted.…”

“…In addition, the existing guidelines for AD management are not specific to children under 2 years, and some treatments recommended by the guidelines are indicated only for children 2 years and older, such as topical calcineurin inhibitors. [10][11][12] Because AD is a common problem, pediatric management guidelines have been published, but are not specific to children under 2 years. [13][14][15][16][17][18][19] Because treatment recommendations are different and undertreatment is more common in this age group, it deserves specific attention.…”

“…In addition, the existing guidelines for AD management are not specific to children under 2 years, and some treatments recommended by the guidelines are indicated only for children 2 years and older, such as topical calcineurin inhibitors. 10-12…”