b'Theirrecommendationabouttheuseofthetopi- [12 fewer to 4 more]). The direct data were too short cal JAK inhibitor product in adolescents and adultand did not contain enough adults (at risk) to cred-patients was noted as being conditional with low-cer- ibly estimate the effect on death, cancer, thrombosis, tainty evidence. The guidelines suggested the follow- or serious infections, according to the report. Stroke ing conditions be considered: was observed in the topical ruxolitinib group in thePatients who place a higher value on certainTRuE-AD trials, but recent data, a mix of observa-larger benefits and safety profiles of othertionalandrandomizeddata,to40weekssuggest topical treatments (e.g., TCS 2-4, tacrolimus)favorable safety.and certain systemic therapies are less likely toIn2021,theU.S.FoodandDrug Administration prefer topical ruxolitinib. announcedtheapprovalofruxolitinibcream,mar- Patients who are immunocompromised,ketedasOpzelura,fortheshort-termandnoncon-immunosuppressed, or have risk factorstinuous chronic treatment of mild-to-moderate AD in for serious infection, cancer, thrombosis,nonimmunocompromised patients age 12 years and or cardiovascular events may prefer otherolder whose disease is not adequately controlled with treatments compared with topical ruxolitinib. topical prescription therapies, or when those therapiesPatients who have not responded to otherare not advisable.topical therapies and/or those who highly value the modest benefits of topical ruxolitinibDiscontinuous Useover the more certain larger benefits of otherBecause the FDA placed a boxed warning label on topical treatments, and ruxolitinibs uncertainall JAK inhibitors in 2022 due to concerns about in-association with an increased risk of cancer,creases in major cardiovascular adverse events and thromboembolism, serious infection, andcancer, as well as, at higher doses, venous throm-mortality, and safety profile of systemicboembolism, serious infections and death from any treatments, might favor topical ruxolitinib. cause, the guideline panel recommended some limi-The panel pointed out the topical treatments system- tations on use of the topical product. Concerns about atic review and NMA, which included three randomsystemic absorption with topical JAK inhibitors are controlled trials and more than 1,400 adolescent andsufficient to limit application of ruxolitinib to less adultparticipantswithmild ADdefinedasmeanthan 20% BSA and use it in a discontinuous manner ~9.5%bodysurfaceareainvolvementandmean[to] decrease the potential for harm, it wrote.EASI ~8comparing, topical ruxolitinib vs. eitherStill, the guidelines recommended the use of oral standard care or TCS 4 (triamcinolone 0.1% cream),JAK inhibitors after careful consideration of risks revealed high or moderate certainty improvements inand possible benefits in adults and adolescents with AD severity (RD 23 more per 100 [6-41 more]), itchmoderate-severe AD refractory, intolerant, or unable (34 more per 100 [20-47 more]), sleep disturbanceto use mid- to high-potency topical treatment and (4 more per 100 [0-10 more]) and quality of life (35systemic treatmentinclusiveofabiologic recom-more per 100 [25 more to 45 more]). mended previously.WhethertopicalruxolitinibreducesflaresisThe authors advised, however, that, in most mild-highly uncertain due to imprecision and the short- moderate patients with AD, the risk with a topical JAK term (4-8 weeks) nature of the available studies thatinhibitor, however, would be predicted to be lower assessed relevant interventions and controls (com- than that with an oral JAK inhibitor. Robust compara-parators), according to the guideline authors, whotive long-term data are required to definitively clarify added, Topical ruxolitinib is slightly more potentserious harms, if any, of using topical ruxolitinib.in improving most patient-important AD outcomesThey urged that patients and clinicians consider-comparedtopimecrolimus(betweenTCS5anding topical ruxolitinib should engage in a discus-TCS 6/7). sion of the potential benefits and harms and establish The article also advised that, overall, adverse eventswhether topical ruxolitinib or another topical or sys-within the time frame were similar between topicaltemic therapy optimally aligns with patient values ruxolitinib and control groups (RD 5 fewer per 100and preferences.45'