ABSTRACT
Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of â¼2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss. The prognosis of AA is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Because these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors. In preclinical trials in mice, tofacitinib successfully prevented AA development and reversed established disease. In our tofacitinib trial in 12 patients with moderate to severe AA, 11 patients completed a full course of treatment with minimal adverse events. Following limited response to the initial dose (5 mg b.i.d.), the dose was escalated (10 mg b.i.d.) for nonresponding subjects. Eight of 12 patients demonstrated ≥50% hair regrowth, while three patients demonstrated <50% hair regrowth, as measured by Severity in Alopecia Tool scoring. One patient demonstrated no regrowth. Gene expression profiles and Alopecia Areata Disease Activity Index scores correlated with clinical response. Our open-label studies of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate to severe AA, providing strong rationale for larger clinical trials using JAK inhibitors in AA. ClinicalTrials.gov ID NCT02299297.
Subject(s)
Alopecia Areata/drug therapy , Autoimmune Diseases/drug therapy , Janus Kinase Inhibitors/therapeutic use , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Adult , Alopecia Areata/diagnostic imaging , Alopecia Areata/immunology , Alopecia Areata/pathology , Autoimmune Diseases/diagnosis , Autoimmune Diseases/immunology , Biopsy , Dose-Response Relationship, Drug , Female , Gene Expression Profiling , Hair Follicle/drug effects , Hair Follicle/growth & development , Hair Follicle/pathology , Humans , Janus Kinase Inhibitors/pharmacology , Janus Kinases/antagonists & inhibitors , Janus Kinases/immunology , Male , Middle Aged , Nitriles , Photography , Pilot Projects , Piperidines/pharmacology , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyrimidines/pharmacology , Pyrroles/pharmacology , Severity of Illness Index , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE. To investigate the effects of weight status, food type and exposure to food and non-food advertisements on children's preference for branded and non-branded foods. DESIGN. A within-subjects, counterbalanced design with control (toy advertisement) and experimental (food advertisement) conditions. Subjects. A total of 37 school students (age: 11-13 years; weight status: 24 lean, 10 overweight, 3 obese). Measurements. Advertisement recall list, two food preference measures; the Leeds Food Preference Measure (LFPM), the Adapted Food Preference Measure (AFPM) and a food choice measure; the Leeds Forced-choice Test (LFCT). RESULTS. Normal weight children selected more branded and non-branded food items after exposure to food advertisements than in the control (toy advertisement) condition. Obese and overweight children showed a greater preference for branded foods than normal weight children per se, and also in this group only, there was a significant correlation between food advertisement recall and the total number of food items chosen in the experimental (food advertisement) condition. CONCLUSION. Exposure to food advertisements increased the preference for branded food items in the normal weight children. This suggests that television food advertisement exposure can produce the same 'obesigenic' food preference response found in overweight and obese children in their normal weight counterparts.
