Linda Stein Gold’s research while affiliated with Henry Ford Health System and other places

Psoriasis, a chronic inflammatory skin condition, can have a significant impact on patients’ quality of life. Adoption of novel and emerging treatments has significantly improved psoriasis care in clinical practice, but challenges remain. The ‘Bridging the Gaps in Challenging Psoriasis’ meeting was held in October 2024 to discuss relevant evidence, knowledge gaps, and best practices pertaining to challenging presentations of psoriasis. This report captures important insights and practice impacting guidance gathered from the panel discussion on five topics. The meeting commenced with an in-depth discussion on managing psoriasis in high-impact areas (e.g., scalp, intertriginous regions, nails, and the palms and soles) followed by a discussion on the importance of identifying and addressing common comorbidities associated with psoriasis. The panel explored key considerations and unique challenges when treating psoriasis in patients with darker skin tones (‘skin of color’) and highlighted the need for tailored therapeutic approaches. A comprehensive dialogue ensued on strategies for managing primary and secondary treatment failures. The session concluded with a concise discussion on the future of psoriasis treatments and pharmacologic therapies currently being developed to manage psoriasis. While discussing various challenging psoriasis scenarios, the dermatology experts emphasized the need to approach psoriasis as a systemic disease and advocated for comprehensive management that addresses both the skin and the broader health of the patient.

Introduction: Lebrikizumab was recently approved in the US for treatment of moderate-to-severe atopic dermatitis. Safety data have been reported from individual trial disclosures and multiple long-term integrated lebrikizumab analyses. Here we present integrated safety data from the US Prescribing Information. Methods: Data were summarized from three datasets: 1) Week 0–16 PBO-controlled analysis (lebrikizumab 250 mg every two weeks [LEBQ2W] versus PBO, presented as monotherapy studies [ADvocate1, NCT04146363; ADvocate2, NCT04178967; and Phase 2b KGAF, NCT03443024] and the topical corticosteroid (TCS) combination study [ADhere, NCT04250337]); 2) Maintenance period of monotherapy studies ADvocate1 and ADvocate2 (LEBQ2W-treated patients who responded at week 16 and received LEBQ2W, LEBQ4W or PBO [LEB withdrawal] to week 52); and 3) Week 0–52/56 analysis (patients treated with LEBQ2W only, or LEBQ2W then LEBQ4W up to 52 or 56 weeks). Study-size-adjusted percentages were calculated for the pooled PBO-controlled analysis and maintenance period. Exposure-adjusted incidence rates (IRs) were number of patients reporting an event per 100 patient-years at risk. Results: PBO-controlled analysis included 338 PBO-treated and 638 LEBQ2W-treated patients in the monotherapy studies and 66 PBO-treated and 145 LEBQ2W-treated patients in the TCS study. During the maintenance period 113, 118, and 60 patients received LEBQ2W, LEBQ4W, and PBO, respectively. In Week 0-52/56 analysis 844 and 147 patients received LEBQ2W and LEBQ2W/Q4W, respectively. For PBO-controlled, adverse reactions that occurred in ≥1% of LEBQ2W-treated patients in monotherapy or TCS studies, and at a higher rate than PBO, were conjunctivitis cluster (monotherapy trials: n=61 [9.6%], LEBQ2W; n=10 [3.0%], PBO; TCS trial: n=7 [4.8%], LEBQ2W; n=0, PBO); injection site reactions (monotherapy trials: n=16 [2.6%], LEBQ2W; n=4 [1.2%], PBO; TCS trial: n=4 [2.8%], LEBQ2W; n=1 [1.5%], PBO); and herpes zoster (HZ) (monotherapy trials: n=3 [0.5%], LEBQ2W; n=0, PBO; TCS trial: n=2 [1.4%] LEBQ2W; n=0, PBO). All events were nonserious; most were mild/moderate severity. No HZ events were considered opportunistic infections or led to treatment discontinuation. In the monotherapy studies, 15 (2.4%) LEBQ2W-treated and 6 (1.8%) PBO-treated patients discontinued treatment due to AEs; in the TCS study, 3 (2.1%) LEBQ2W-treated and 0 PBO-treated patients discontinued treatment due to AEs. Eosinophilia and keratitis cluster were reported in <1% of LEBQ2W-treated patients. During the maintenance period there were 2 (1.8%), 12 (10.1%) and 5 (8.3%) conjunctivitis cluster events in LEBQ2W, LEBQ4W, and PBO, respectively. Atopic keratoconjunctivitis was reported by 1 (0.8%) patient in LEBQ4W; vernal keratoconjunctivitis was reported by 1 (0.9%) patient in LEBQ2W; no events reported in PBO. In the Week 0–52/56 analysis, the IR of conjunctivitis was 18.3 for LEBQ2W and 20.6 for LEBQ2W/Q4W. Conclusions: For the adverse reactions reported in the lebrikizumab US Prescribing Information, the majority were mild to moderate in severity and few led to treatment discontinuation.

Background Antibiotic resistance is growing globally, with multiple countries reporting resistance in >50% of Cutibacterium acnes (C. acnes) strains. Combination formulations of an antibiotic and the antimicrobial benzoyl peroxide (BPO) may reduce this resistance risk, especially with prolonged use. This 4-part study tested susceptibility of 31 C. acnes clinical strains and development of resistance to antibiotics alone or combined with BPO. Methods C. acnes susceptibility to single-drug antibiotics was assessed via minimum inhibitory concentration (MIC) values obtained from epsilometer tests, with lower MIC indicating higher susceptibility. Susceptibility to fixed-dose antibiotic/BPO combination products was determined by measuring the zone of inhibition using the agar diffusion method, with larger diameter indicating increased bacterial inhibition. The effect (synergistic, additive, antagonistic, or indifferent [no interaction]) of combining clindamycin with BPO on C. acnes inhibition was evaluated using a checkerboard assay, wherein 2 test compounds are combined in varying concentrations. Resistance development was assessed using serial passage of bacterial cultures in increasing concentrations of clindamycin alone or in combination with BPO. Results All tested antibiotics (clindamycin, doxycycline, erythromycin, and minocycline) exhibited similar activity. C. acnes susceptibility was variable, with some strains having elevated MIC values—an indication of resistance—against different antibiotics. For 6 strains resistant to clindamycin alone (inhibitory zone=0 cm), formulations with BPO enhanced activity against the same isolates (range: 0.8–2.2 cm). Of 7 acne-associated strains, combining clindamycin and BPO had an additive effect against 4, and no interaction against 3. Bacterial cultures repeatedly exposed to the combination of clindamycin and BPO did not develop antibiotic resistance, which occurred with exposure to clindamycin alone. Conclusion Overall, antibiotic susceptibility was highly dependent on the C. acnes strain, and antibiotic formulations with BPO exhibited enhanced activity against less susceptible strains. Fixed combinations of BPO with an antibiotic may improve antimicrobial activity and protect against resistance development.

Introduction Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the only fixed-dose, triple-combination approved for acne. In phase 2 and 3 studies, CAB demonstrated superior efficacy to vehicle and component dyads. This post hoc analysis examined efficacy/tolerability of CAB in 147 self-identified Hispanic/Latino participants (referred to as Hispanic). Methods Data were pooled from one phase 2 (NCT03170388) and two phase 3 (NCT04214652, NCT04214639) double-blind, 12-week studies. Eligible participants aged ≥9 years with moderate to severe acne were randomized to once-daily CAB or vehicle. Endpoints included ≥2-grade reduction from baseline in Evaluator’s Global Severity Score with clear/almost clear skin (treatment success) and inflammatory/noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were assessed. Results At week 12, 56.2% of CAB-treated participants achieved treatment success vs 18.4% with vehicle (p < 0.001). Reductions in inflammatory/noninflammatory lesions were 77.1%/76.2% with CAB vs 56.4%/45.0% with vehicle, respectively (p < 0.001, all). CAB TEAE rates were similar to overall study populations (27.0% vs 24.6%-36.2%). Baseline hyperpigmentation scores decreased from 0.6 to 0.3 (1 = mild) at week 12 with CAB. CAB gel was efficacious, safe, and well tolerated in Hispanic participants. Limitations include lack of Fitzpatrick skin phototype and short study duration. Conclusions This study provides support for acne treatment with CAB in ethnically diverse populations.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the USA and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. In POETYK PSO-1 and PSO-2, deucravacitinib was superior to placebo and apremilast and well tolerated in patients with plaque psoriasis. Patients who completed PSO-1/PSO-2 could enroll in the POETYK long-term extension (LTE) trial. This analysis evaluates the effects of deucravacitinib on laboratory parameters. POETYK PSO-1 and PSO-2 were 52-week, phase 3, double-blinded trials that randomized patients 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At week 52, eligible patients enrolled in POETYK LTE and received open-label deucravacitinib. Mean changes from baseline in laboratory parameters, laboratory adverse events (AEs), and laboratory AEs resulting in discontinuation were evaluated over 3 years. A total of 1519 patients received one or more doses of deucravacitinib across trials. Total exposure over 3 years was 3294.3 person-years. No clinically relevant mean changes were observed in laboratory parameters. Grade ≥ 3 laboratory AEs were infrequent during the 1-year period, with incidence rates remaining stable in patients treated with deucravacitinib through 3 years. Most laboratory AEs remained at the same grade; shifts to higher grades were infrequent, with most increases being to grade ≤ 2. Discontinuations due to laboratory AEs were rare. Deucravacitinib did not result in clinically meaningful changes in laboratory parameters over 3 years, including changes seen with Janus kinase (JAK) 1,2,3 inhibitors. Grade ≥ 3 laboratory AEs and discontinuations were rare. ClinicalTrials.gov identifier, POETYK PSO-1 (NCT03624127), POETYK PSO-2 (NCT03611751), POETYK LTE (NCT04036435).

Background Atopic dermatitis (AD) is a chronic, immune‐mediated, inflammatory skin disorder affecting a heterogeneous population. Most patients with mild‐to‐moderate AD are treated with topical medication. Objectives To gain an understanding of the management of mild‐to‐moderate AD with topical treatments by examining the practices of dermatologists worldwide using a questionnaire. Methods Participants from North America, the Middle East, Asia, South America and the United Kingdom completed an electronic questionnaire composed of 43 questions assessing their clinical practice with topical treatment for patients with mild‐to‐moderate AD among different age groups ( < 2, 2−12 and > 12 years) and disease severity (mild or moderate AD). Results Seventeen dermatologists completed the questionnaire. For patients of all ages with mild‐to‐moderate AD, nearly all participants indicated that topical corticosteroids (TCSs) are the first‐line topical treatment for a duration of ≤ 4 weeks before reassessment. Less‐potent TCSs were preferred for younger patients and for sensitive regions of the body. Time until treatment re‐evaluation was guided by disease severity: the greater the disease severity, the shorter the time until re‐evaluation (1 week to 4 months). In all age groups, after initial treatment, most participants would continue the regimen previously prescribed, switch to a non‐TCS agent (e.g., a topical calcineurin inhibitor, crisaborole or topical JAK inhibitor), or reduce the dose. All participants would utilize TCSs with or without non‐TCS agents for treating flares depending on patient age and affected region(s) of the skin. Infection, drug‐related adverse effects, worsening AD, corticophobia and limited access to topical pharmacologic treatment were the main reasons for deviation from the standard regimen. Conclusions Management of mild‐to‐moderate AD in practice is influenced by several patient‐specific factors, access to specialist care and therapies, safety concerns and limitations associated with treatment options.

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. In the phase 3b/4 PSORIATYK SCALP trial, deucravacitinib was superior to placebo at Week 16 in patients with moderate to severe scalp psoriasis, including those with less extensive overall psoriasis (total body surface area [BSA] involvement ≥3%). This analysis evaluates the time to meaningful improvement in patient-reported outcomes (PROs) in patients treated with deucravacitinib vs placebo in the PSORIATYK SCALP trial. Methods: Patients aged ≥18 years with moderate to severe scalp psoriasis were randomized 1:2 to once-daily placebo or deucravacitinib 6 mg. Evaluated PROs included scalp-specific itch, pain and flaking, and whole-body itch numeric rating scales (NRS), Scalpdex, and Dermatology Life Quality Index (DLQI). Times to meaningful improvement in these PROs (≥4-points reduction from baseline for NRS measures and DLQI; ≥20-point reduction for Scalpdex) were estimated using Kaplan-Meier methods. Cox regression models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for response up to 16 weeks. Results are reported for the overall population and for subgroups of patients with baseline BSA 3%–10% and BSA >10% at baseline. Results: In the overall population (placebo: n = 51; deucravacitinib: n = 103), patients treated with deucravacitinib had a shorter median time to meaningful improvement and were significantly more likely to achieve response by Week 16 for all PROs compared with patients receiving placebo (P < 0.05). In patients treated with deucravacitinib, the median time (95% CI) to meaningful improvement was 9.0 (8.0, 16.3), 8.7 (2.6, 15.7), 8.0 (4.1, 8.1), 8.3 (4.1, 15.7), and 2.1 (1.4, 4.3) weeks for scalp-specific itch, pain, and flaking NRS, whole-body itch NRS, and DLQI, respectively. The median time to meaningful improvement was also shorter with deucravacitinib vs placebo for all PROs in both the BSA 3%–10% and BSA <10% subgroups. Conclusion: Deucravacitinib was associated with a shorter time to meaningful improvement vs placebo across evaluated PROs in the overall population and in BSA subgroups.

Background: Topical treatment of acne—particularly with retinoids—often incurs a transient period of dermal irritation characterized by erythema, scaling, and other dermal changes that may reflect the same mechanisms of action by which acne pathophysiology is addressed. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel demonstrated efficacy in the treatment of acne, with a safety/tolerability profile typical of topical acne treatment. The objective of this post-hoc analysis is to determine whether CAB efficacy was related to occurrence of cutaneous safety/tolerability events. Methods: Data were pooled from 4 double-blind, 12-week studies of participants with moderate-to-severe acne. Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). Cutaneous safety/tolerability assessments of erythema and scaling (investigator-assessed) and itching, burning, and stinging (participant-assessed) were graded on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). To determine if CAB efficacy was associated with cutaneous events, efficacy endpoints at week 12 were compared for CAB-treated participants who experienced no increase versus ≥1-grade (any) increase in any safety/tolerability score at weeks 2, 4, or 8. Results: At week 12, CAB-treated participants experiencing any safety/tolerability event (n=411) had significantly greater rates of treatment success and IL reductions, and numerically greater NIL reductions, than those without events (n=188; treatment success: 55.0% vs 43.0%; P<0.01; IL reductions: 79.1% vs 72.3%; P<0.001; NIL reductions: 73.1% vs 68.1%). At weeks 2, 4, and 8, IL/NIL reductions were significantly greater among participants experiencing any cutaneous event than those without events (P<0.05, all). Overall, improved efficacy appeared to be driven by events of scaling, itching, and burning. Conclusions: Across four clinical studies, CAB-treated participants who experienced safety/tolerability events at weeks 2, 4, or 8 also experienced greater lesion reductions across 12 weeks of treatment and greater rates of treatment success at week 12. These findings are consistent with the theory that early instances of cutaneous irritation during topical acne treatment may reflect therapeutic mechanisms of action. Setting patient expectations regarding the potential for transient irritation during treatment may contribute to greater adherence and efficacy with CAB gel. Funding: Ortho Dermatologics

Introduction: In ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, an Organon Company) once daily (QD) demonstrated superior efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability from ADORING 3. Methods: Patients from ADORING 1 and 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild AD, or moderate or severe AD, that did not meet ADORING 1 or 2 inclusion criteria, received tapinarof cream 1% QD for up to 48 weeks. Endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™]=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Patients entering with vIGA-AD™≥1 received tapinarof until vIGA-AD™=0. Those entering with or achieving vIGA-AD™=0 discontinued tapinarof and were assessed for maintenance of vIGA-AD™=0 or 1 (treatment-free interval). Patients with vIGA-AD™≥2 were re-treated until vIGA-AD™=0. Results: 728 patients enrolled; 83.0% pediatric (2–17 years). Overall, 51.9% entered with or achieved vIGA-AD™=0, and 81.6% entered with or achieved vIGA-AD™=0 or 1 at least once during ADORING 3. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent treatment-emergent adverse events (TEAEs) were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Trial discontinuations due to TEAEs were low (2.6%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated, even on sensitive skin. Conclusions: Tapinarof cream monotherapy was well tolerated and demonstrated high rates of complete disease clearance (51.9%) in patients down to age 2 years with AD. After discontinuing tapinarof, clear or almost clear skin was maintained for 79.8 consecutive days. No new safety signals and low rates of trial discontinuation were observed.

Background: Acne treatment can take weeks to result in noticeable improvements, which may diminish patients’ perception of treatment effectiveness and negatively affect treatment adherence. Acne treatments that deliver early visible improvements may encourage treatment adherence and bolster overall treatment effectiveness. Combination topical treatments that target multiple acne pathophysiological pathways are more efficacious than monotherapies and simplifying the treatment regimen by delivering multiple active ingredients as fixed combinations may improve adherence. Objective: To evaluate early acne improvements in clinical trials of fixed-combination acne topicals. Methods: Week 4 efficacy data for fixed-combination topical treatments were gathered from US Food and Drug Administration medical reviews, prescribing information, and/or publications of pivotal phase 2 and phase 3 clinical trials of 7 acne topicals, comprising fixed combinations of adapalene (ADAP), benzoyl peroxide (BPO), clindamycin phosphate (CLIN), and tretinoin. For the triple-combination formulation (CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel), data from a nonpivotal phase 2 study with dyad combination treatment arms were also included. Outcomes included reductions from baseline in inflammatory lesions (ILs) and noninflammatory lesions (NILs) and treatment success (≥2-grade reduction in global acne severity score and clear/almost clear skin). Results: At week 4, IL reductions from baseline ranged from 32-54% while NIL reductions ranged from 25-45%. Rates of treatment success ranged from 3-12%. Overall, efficacy was greatest with triple-combination CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel (IL: 54-55%; NIL: 43-45%; treatment success: 8-12%), followed by combinations of ADAP/BPO (IL: ~42-48%; NIL: ~38%; treatment success: 4-~7%). None of the branded topical products were evaluated in a head-to-head study. Conclusions: In pivotal clinical trials of topical fixed-combination formulations for acne, triple-combination CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel yielded greater lesion reductions and rates of treatment success after 4 weeks of treatment than dyad formulations. Even greater differences may be expected with real-world world use, as early improvements may foster better long-term outcomes by increasing patients’ confidence in and adherence to the treatment. Funding: Ortho Dermatologics