2) This program is supported by educational grants from Pfizer & Incyte. Accreditation statement & faculty disclosures at https://t.co/UB9pTq270E. This program is intended for #healthcare providers & posts from your ONLY #dermatology Twitter #CME/CE network!
— @derm_ce (@derm_ce) July 26, 2022
4) Of late there is substantial interest in #topical #Janus_kinase (#JAK) inhibitors for treatment of #AD. New topical JAK inhibitors include #ruxolitinib (which blocks JAK1/2) and delgocitinib (pan-JAK inhibitor).
— @derm_ce (@derm_ce) July 26, 2022
6) So let's take a deeper dive! pic.twitter.com/T1LHQuuwGJ
— @derm_ce (@derm_ce) July 26, 2022
7b) This ➡️increased susceptibility to external insults, such as microbes and proinflammatory allergens, toxins, and irritants (🔓https://t.co/NinwwhCkci). Response to these ➡️activation of #chemokine receptors (esp IL-4, IL-13, IL-31, IL-33). pic.twitter.com/hl1iUfhs1r
— @derm_ce (@derm_ce) July 26, 2022
7d) Once an extracellular #cytokine binds to its receptor, #JAK proteins activate & then phosphorylate #STAT proteins, which move to the nucleus and activate downstream gene transcription.
— @derm_ce (@derm_ce) July 26, 2022
9) The #JAK–#STAT signaling pathway mediates effects of several key #cytokines on immune cells, keratinocytes, and peripheral sensory neurons that lead to inflammation and itch, including IL-4, IL-5, IL-13, IL31, IL-22, and TSLP
See https://t.co/kgmAkm9DMO. pic.twitter.com/JLzAkE4fM5— @derm_ce (@derm_ce) July 26, 2022
10b) . . . #systemic therapy for #AD with #JAK inhibitors is available. In this program we'll focus on the more recently available #topical JAK inhibitor therapy: #ruxolitinib. pic.twitter.com/yzJnoice9b
— @derm_ce (@derm_ce) July 26, 2022
12a) A Ph 2 study (🔓https://t.co/l0gybRd3l3) by led by @derm_ce faculty @itchdoctor, 307 adult patients with mild-mod #AD w/ 3-20% affected body surface area were randomized for 8 weeks of double-blind treatment to #RUX at one of 4 doses, vehicle, or #triamcinolone cream.
— @derm_ce (@derm_ce) July 26, 2022
12c) The primary end point was the comparison between 1.5% RUX cream BID and vehicle in mean percentage change from baseline in Eczema Area and Severity Index (EASI) at week 4. pic.twitter.com/9ffle6vSTZ
— @derm_ce (@derm_ce) July 26, 2022
13b) At that timepoint, both 1.5% RUX groups (QD or BID) reported greater improvement compared with triamcinolone. Rapid ⬇️in the itch numerical rating scale score occurred w/in 36h &were sustained through 12 weeks.
— @derm_ce (@derm_ce) July 26, 2022
14) In a separate analysis (🔓https://t.co/gIrc9upvKP), effects of #ruxolitinib cream on #pruritus & quality of life #QoL in atopic dermatitis #AD were presented.
— @derm_ce (@derm_ce) July 26, 2022
15b) Patients rated itch severity based on their worst itching in the past 24 h using an 11-point scale from 0 (“no itch”) to 10 (“worst itch imaginable”). This eval was validated in daily assessment of #AD symptoms in adults with moderate-to-severe AD. pic.twitter.com/VIvxNK3GGd
— @derm_ce (@derm_ce) July 26, 2022
16) Improvements in itch #NRS and Skindex-16 were observed with #RUX cream. Overall, 42.5% of patients who applied 1.5% RUX BID experienced a minimal clinically important difference in itch w/in 36h of treatment & (vehicle, 13.6%; P<.01); near-max improvement was seen by week 4. pic.twitter.com/zmAdfage2x
— @derm_ce (@derm_ce) July 26, 2022
18) The authors concluded that #RUX cream provides clinically meaningful reduction in #itch and #QoL burden. Topical RUX was approved by @US_FDA for the treatment of mild to moderate atopic dermatitis #AD in September 2021.
— @derm_ce (@derm_ce) July 26, 2022
20) Show us what you learned by marking your best answer. Correct responses–and your link to 🆓CE/#CME to follow when we see you here tomorrow. 👍to @DrCandriceHeath @nationaleczema @DrJanPeds @aaron_drucker @JosephMerolaMD @paller_lab @Dr_BaderAlOmair @DrJoelGelfand
— @derm_ce (@derm_ce) July 26, 2022
22) Yesterday's quiz (tweet 19)? It's D: both A & B, i.e., #ruxolitinib inhibits both #JAK1 & #JAK2 receptors does. Recent work (🔓https://t.co/PlT85QwHtu) suggests that inhibiting both ⬇️itch AND inflammation, likely by modulating inflammatory dendritic epidermal cells #IDECs
— @derm_ce (@derm_ce) July 27, 2022
24a) Indeed, there are 2⃣: Topical #Ruxolitinib Evaluation in #Atopic_Dermatitis Study 1 (NCT03745638) & Study 2 (NCT03745651) #TRuE_AD enrolled patients aged ≥12 yrs with AD for ≥2 yrs, an Investigator's Global Assessment score of 2/3, and 3%-20% affected body surface area.
— @derm_ce (@derm_ce) July 27, 2022
25a) Looking at the 2 studies in aggregate, significantly more patients achieved Investigator's Global Assessment treatment success with 0.75% RUX cream (50.0%/39.0%) & 1.5% RUX cream (53.8%/51.3%) versus vehicle (15.1%/7.6%; P < .0001) at week 8.
— @derm_ce (@derm_ce) July 27, 2022
26) The authors concluded that #RUX cream showed anti-inflammatory and prompt antipruritic effects with superior efficacy versus vehicle and was well tolerated. pic.twitter.com/aOWVhzYdSK
— @derm_ce (@derm_ce) July 27, 2022
28) So way back up in tweet 4 we mentioned topical #delgocitinib (a pan-JAK blocker) was approved in Japan for #AD. Clinical development of the topical formulation is also underway for #alopecia_areata, chronic🖐️eczema, discoid lupus, & #AD in several countries 🌎🌏🌍
— @derm_ce (@derm_ce) July 27, 2022
30) In summary, there's lots of promise here. The #JAK_STAT signaling pathway is key to the pathophysiology of numerous #inflammatory #dermatoses are driven by soluble inflammatory mediators.
— @derm_ce (@derm_ce) July 27, 2022
32) It appears that #topical application avoids the rare #toxicity seen with #systemic administration of #JAK-inhibitors. #AD is a pervasive problem in kids & adults and it's great to envision new, targeted, effective therapies!
— @derm_ce (@derm_ce) July 27, 2022
34) Now go claim your 🆓certificate #physicians #physicianassociate #nurses #nursepractitioners #pharmacists at https://t.co/eke9M3dwdz. pic.twitter.com/JJfWyq8iud
— @derm_ce (@derm_ce) July 27, 2022
