Introduction
Current AA Treatment Paradigm
AA in the Footsteps of Psoriasis
Agent | Trade name (manufacturer) | Target | Mechanism | Drug | Rationale for AA | ClinicalTrials.gov |
---|---|---|---|---|---|---|
Broad T cell inhibition | ||||||
Ruxolitinib | Jakafi (Novartis) | JAK1 = JAK2 > Tyk2 ⋙ JAK3 | Broad T cell Inhibition, including Th1, Th2, Th9, TYK2 targeting adds IL-23 antagonism | Oral small molecule | NCT01950780 | |
Tofacitinib | Xeljanz (Pfizer) | JAK3 > JAK1 ≫ JAK2 | NCT02312882 NCT02197455 | |||
Baricitinib | – (Eli lilly) | JAK1 = JAK2 ⋙ TYK2 > JAK3 | NCT02299297 | |||
PF-06651600 | – (Pfizer) | JAK3 | JAK3 is speculated to be the main JAK member active in AA | NCT02974868 | ||
PF-06700841 | – (Pfizer) | TYK2/JAK1 | Possible therapeutic benefit relying on the efficacy of other JAK inhibitors | |||
INCB018424 phosphate cream | – (Incyte Corporation) | JAK1 = JAK2 > Tyk2 ⋙ JAK3 | Local inhibition of broad T cell activation | Topical JAK inhibitor | Possible effectiveness relying on efficacy of oral JAK inhibitors (ruxolitinib) | NCT02553330 |
Apremilast | Otezla (Celgene) | PDE4 | Th1, Th2, possibly IL-23/Th17 | Oral small molecule | Efficacious in AA mouse models [65] | NCT02684123 |
Abatacept | Orencia (BMS) | CD80/86 | Inhibition of broad T cell activation | CTLA4-Ig FP | Efficacious in preventing induction of AA in mouse models [71] | NCT02018042 |
IL-23 inhibition | ||||||
Ustekinumab | Stelara (Janssen) | IL-12/IL-23p40 | Direct Th17/IL-23 and Th1 inhibition, but possibly also Th2 inhibition | Anti-p40 mAb | Efficacious in a proof-of-concept human study [15]. Large, randomized placebo-controlled clinical trials are needed | – |
Secukinumab | Cosentyx (Novartis) | IL-17A | Direct IL-17 inhibition, but possibly also Th17/IL-23 inhibition | Anti-IL-17A mAb | NCT02599129 | |
Th2 antagonism | ||||||
Dupilumab | – (Regeneron/Sanofi) | IL-4Rα | Broad Th2 inhibition—IL4 and IL-13 | Anti-IL-4Rα mAb | – | |
Tralokinumab | – (AstraZeneca) | IL-13 | Narrow Th2 inhibition—only IL-13 | Anti-IL-13 mAb | NCT02684097 |
Broad T Cell Antagonism
JAK Inhibitors
PDE4 Inhibition
Abatacept
A Few Broad T Cell Antagonists That Are Ineffective for AA
Agent | Trade name (manufacturer) | Target | Mechanism | Drug | Data for AA |
---|---|---|---|---|---|
Alefacept | Amevive (Astellas) | CD2 | Broad T cell inhibition | LFA-3-Ig FP | No benefit in an AA multicenter, double-blind, randomized, placebo-controlled clinical trial [77] |
Efalizumab | Raptiva (Genentech/Merck) | CD11a | Anti-CD11a mAb | No benefit in an AA double-blind, randomized, placebo-controlled clinical trial [79]. Withdrawn from the market in 2009 because of PML cases | |
Anti-TNF (infliximab, adalimumb, etanercept) | Remicade (Janssen), Humira (Abbvie), Enbrel (Amgen) | TNF | Anti-TNF mAb (infliximab, adalimumab), TNFR-Ig FP (etanercept) |