Background: GBR 830 is a humanized mAb against OX40, a costimulatory receptor on activated T cells. OX40 inhibition might have a therapeutic role in T cell-mediated diseases, including atopic dermatitis (AD). Objective: This exploratory phase 2a study investigated the safety, efficacy, and tissue effects of GBR 830 in patients with AD. Methods: Patients with moderate-to-severe AD (affected body surface area, > _10%; Eczema Area and Severity Index score, > _12; and inadequate response to topical treatments) were randomized 3:1 to 10 mg/kg intravenous GBR 830 or placebo on day 1 (baseline) and day 29. Biopsy specimens were collected (n 5 40) at days 1, 29, and 71. Primary end points included treatment-emergent adverse events (TEAEs) and changes from baseline in biomarkers (epidermal hyperplasia/cytokines) at days 29 and 71. Results: GBR 830 was well tolerated, with equal TEAE distribution (GBR 830, 63.0% [29/46]; placebo, 63.0% [10/16]). One serious TEAE in the GBR 830 group was deemed unrelated to study drug. At day 71, the proportion of intent-to-treat subjects achieving 50% or greater improvement in Eczema Area and Severity Index score was greater with GBR 830 (76.9% [20/26]) versus placebo (37.5% [3/8]). GBR 830 induced significant progressive reductions in T H 1 (IFN-g/CXCL10), T H 2 (IL-31/CCL11/CCL17), and T H 17/T H 22 (IL-23p19/IL-8/ S100A12) mRNA expression in lesional skin. Significant progressive reductions until day 71 in the drug group were seen in OX40 1 T cells and OX40L 1 dendritic cells (P < .001). Hyperplasia measures (thickness/keratin 16/Ki67) showed greater reductions with GBR 830 (P < .001). Conclusions: Two doses of GBR 830 administered 4 weeks apart were well tolerated and induced significant progressive tissue and clinical changes until day 71 (42 days after the last dose), highlighting the potential of OX40 targeting in patients with AD.

IMPORTANCE Vibration has been shown to decrease injection site pain in patients; however, to date, this effect has not been assessed for patients who catastrophize pain (ie, patients who anticipate a higher pain level). The anticipation of a pain score greater than 4 on the 11-point Numeric Rating Scale (NRS) has been associated with an increase in a patient's perception of procedural pain.OBJECTIVE To assess the efficacy of vibration during cutaneous anesthetic injection for dermatologic surgery for patients who catastrophize pain (NRS score >4) and patients who do not (NRS score Յ4).DESIGN, SETTING, AND PARTICIPANTS Randomized, parallel-group clinical trial from June 19 to September 4, 2018, at a tertiary dermatologic surgery clinic among 87 adults undergoing cutaneous cancer removal surgery. Patients completed a preprocedural questionnaire detailing their baseline pain, anticipated pain, and drug use. Analysis was performed on an intent-to-treat basis.INTERVENTIONS Use of a vibratory anesthetic device (VAD) on the treatment site prior to anesthetic injection in the on (VAD ON) or off (VAD OFF) mode.MAIN OUTCOMES AND MEASURES Pain was reported using the 11-point NRS (where 0 indicates no pain and 11 indicates the worst pain imaginable). A minimum clinically important difference of 22% or more and a substantial clinically important difference of 57% or more were used to assess the efficacy of vibration in patient-reported NRS score during anesthetic injection (iNRS score).RESULTS A total of 87 patients were included, with 101 unique events reported (among the unique events, 37 were reported in women and 64 were reported in men; mean [SD] age, 66.0 [11.3] years). The mean (confidence level [CL]) iNRS score for patients who catastrophized pain was 2.27 (0.66) compared with 1.44 (0.39) for patients who did not (P = .03). A 38.9% decrease in mean (CL) iNRS score was reported with VAD ON compared with VAD OFF in all participants (1.24 [0.38] vs 2.04 [0.54]). Patients who catastrophized pain reported a 25.5% decrease in mean (CL) iNRS score with VAD ON vs VAD OFF (1.91 [0.99] vs 2.57 [0.98]), and patients who did not reported a 79.4% decrease (1.02 [0.40] vs 1.84 [0.66]). VAD ON was the only statistically significant variable to affect iNRS score (F statistic, 2.741; P = .03).CONCLUSIONS AND RELEVANCE This trial demonstrates that those who catastrophize pain prior to a procedure report a higher perceived level of pain. The application of vibration during local anesthetic injection resulted in a minimum clinically important difference in pain level for patients who catastrophize pain and a substantial clinically important difference in pain level for patients who do not. LEVEL OF EVIDENCE 2.TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03467685

BACKGROUND-Inadequate pain reduction during anesthetic injection is a significant medical and surgical problem. Vibratory distraction reduces this pain; however, there are minimal data identifying those who respond best. OBJECTIVE-To quantify analgesia from vibration before anesthetic injection.MATERIALS AND METHODS-In this partially blinded, single-institution trial, adult participants were randomized to intervention (vibratory anesthetic device, VAD ON) or placebo (VAD OFF). Pain was assessed using the 11-point numeric rating scale (NRS). Relative reduction in NRS between VAD OFF and ON was used to identify minimum clinically important and substantially clinically important difference in pain.RESULTS-One hundred one tested sites from 87 subjects were assessed. Sixty-three percent were men with a median age of 66 years. From univariate analysis, males, subjects aged <60, and head and neck (HN) treated subjects had a significant reduction in NRS (p < .05). Multivariate analysis identified NRS reductions in females <60 (p = .012), males ≥70 (p = .002), females and males treated on HN (p = .048 and p = .035, respectively), and males ≥70 treated on HN (p = .012). Substantially clinically important difference (≥57% NRS reduction) included subjects <60, females <70, HN treatment aged 60 to 69, males ≥70, and females treated on HN.CONCLUSION-Vibratory anesthetic device reduces pain during anesthetic injection, primarily for HN treatments and older male subjects.

BACKGROUND-Dermatologic surgery is associated with low postoperative infection rates, averaging from approximately 1% to 4.25%. Often, postoperative infections are treated empirically based on clinical diagnosis of infection, given it can take 48 to 72 hours for a wound culture to identify a pathogen. OBJECTIVE-We aimed to evaluate the efficacy of empiric antibiotics in dermatologic surgery postoperative infections and if wound cultures change postoperative antibiotic therapy.METHODS-A 7-center, retrospective analysis of postoperative infections, with culture data, in dermatologic surgery patients was performed.RESULTS-Of 91 cases of clinically diagnosed postoperative infection, 82.4% (n = 75) were successfully treated with empiric oral antibiotics (95% confidence interval [0.73-0.89], p < .0001).

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