SUPPLEMENT ARTICLE: A Novel Drug Delivery Method: Retrometabolic Drug Design.

Soft drugs, a class of retrometabolic drug design, contain a metabolically sensitive moiety that promotes rapid metabolism to inactive metabolites after exerting activity at its target site. The goal of soft drugs is to reduce systemic toxicity while enhancing local efficacy. Soft drugs have been approved for use in multiple medical specialties, such as the soft corticosteroid loteprednol etabonate for treatment of inflammatory ophthalmic disorders and soft beta-blocker derivatives for treatment of hypertensive emergencies in cardiology. Soft drugs have also found widespread use in the field of dermatology. In the setting of topical drug administration, soft drugs minimize the risk of systemic drug absorption and unwanted side effects. Soft janus kinase caspase 1 (JAK) inhibitors, soft transient receptor potential vanilloid (TRPV1), and soft estrogens among others have been explored as therapeutic options for a variety of inflammatory and autoimmune dermatologic conditions. The soft anticholinergic sofpironium bromide represents the latest expansion of soft drug use in dermatology for the treatment of primary axillary hyperhidrosis (PAH). A derivative of glycopyrronium, sofpironium bromide consists of a chemically modified structure that allows the drug to undergo rapid hydrolytic deactivation, and thus minimize the significant side effects associated with traditional anticholinergic drugs. Sofpironium bromide has demonstrated efficacy and safety for treatment of PAH in Phase II and Phase III clinical trials in Japan and the United States. Given the promising results from these studies, sofpironium bromide, in addition to other soft drugs under investigation, highlights the growing utility of retrometabolic drug design in dermatology. J Drugs Dermatol. 2022;21:4(Suppl 2):s5-10.

Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax): Evaluation of Measurement Performance.

BACKGROUND: Clinical trials of primary axillary hyperhidrosis (AHH) require rigorous measurement of AHH severity from the patient’s perspective. Previously, we reported conceptualization and item content development for the Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) scale. OBJECTIVE: To evaluate the psychometric performance and estimate clinically meaningful change scores for the HDSM-Ax in a Phase IIb clinical study of sofpironium bromide gel for AHH. METHOD: HDSM-Ax measurement performance was analyzed in trial response data using two psychometric paradigms: Classical Test and Rasch Measurement Theories (CTT; RMT). HDSM-Ax meaningful change scores were estimated from anchor-based methods using two global summary questions of hyperhidrosis severity and the Hyperhidrosis Disease Severity Score (HDSS). RESULTS: HDSM-Ax satisfied CTT and RMT criteria as a fit-for-purpose outcome measure in AHH clinical trials. Within-person anchor-based analyses indicated a 1-point change in HDSM-Ax severity score (range, 0–4) represents a clinically meaningful change in AHH severity. CONCLUSION: HDSM-Ax is a well-defined and reliable measure of AHH severity. A 1-point change in HDSM-Ax score is clinically meaningful. J Drugs Dermatol.20(4):410-418. doi:10.36849/JDD.5569.

Efficacy and safety of topical sofpironium bromide gel for the treatment of axillary hyperhidrosis: A phase II, randomized, controlled, double-blinded trial.

BACKGROUND: Primary axillary hyperhidrosis has limited noninvasive, effective, and well-tolerated treatment options. OBJECTIVE: To evaluate the topical treatment of axillary hyperhidrosis with the novel anticholinergic sofpironium bromide. METHODS: A phase II, multicenter, randomized, controlled, double-blinded study. Participants were randomized to 1 of 3 dosages or vehicle, with daily treatment for 42 days. Coprimary end points were the percentage of participants exhibiting ≥1-point improvement in the Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) score by logistic regression, and change in HDSM-Ax as a continuous measure by analysis of covariance. Pair-wise comparisons were 1-sided with α = 0.10. RESULTS: At the end of therapy, 70%, 79%, 76%, and 54% of participants in the 5%, 10%, 15%, and vehicle groups exhibited ≥1-point improvement in HDSM-Ax (P < .05). Least-square mean (SE) changes in HDSM-Ax were -2.02 (0.14), -2.09 (0.14), 2.10 (0.14), and -1.30 (0.14) (all P ≤ .0001). Most treatment-related adverse events were mild or moderate. LIMITATIONS: Not powered to detect changes in gravimetric sweat production. CONCLUSION: Sofpironium bromide gel produced meaningful reductions in hyperhidrosis severity and had an acceptable safety profile.

Anti-tubercular therapy causing Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is an idiosyncratic drug reaction following a characteristic long latency period. It is previously known as drug induced delayed multiorgan hypersensitivity syndrome (DIDMOHS) or drug induced hypersensitivity (DIHS). The syndrome is manifested by wide range of clinical symptomatology that hold a potential to be life threatening but still is under recognised. The major drugs that cause DRESS syndrome are anticonvulsants, followed by sulfonamides and many anti-in˜ ammatory drugs.Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is an idiosyncratic drug reaction following a characteristic long latency period. It is previously known as drug induced delayed multiorgan hypersensitivity syndrome (DIDMOHS) or drug induced hypersensitivity (DIHS). The syndrome is manifested by wide range of clinical symptomatology that hold a potential to be life threatening but still is under recognised. The major drugs that cause DRESS syndrome are anticonvulsants, followed by sulfonamides and many anti-inflammatory drugs.