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Few treatments for alopecia areata have demonstrated sustained efficacy. Evaluate the efficacy and safety of continued ritlecitinib treatment to week 48 in patients with alopecia areata with or without target efficacy responses at week 24. Patients aged ≥12 years received daily ritlecitinib (±4-week loading dose): 200/50 mg, 200/30 mg, 50 mg, or 30 mg. Patients with clinical response at week 24, based on a Severity of Alopecia Tool (SALT) score ≤20 and ≤10, were evaluated for sustained response through week 48. Nonresponders at week 24 were assessed for response through week 48. Among ritlecitinib-treated patients with SALT score ≤20 and ≤10 responses at week 24, ≥85% and ≥68%, respectively, sustained these responses through week 48. Of those with a SALT score >20 at week 24, 22% to 34% achieved a SALT score ≤20 at week 48. Of those with a SALT score >10 at week 24, 20% to 26% achieved a SALT score ≤10 at week 48. Safety was similar across subgroups. Small sample size. Hair regrowth was sustained through week 48 in patients with response at week 24. Up to one-third of patients who did not meet target efficacy at week 24 achieved response with continued ritlecitinib treatment. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated the safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo for 24 weeks. The primary end point was the percentage of patients achieving a Severity of Alopecia Tool score ≤20. A key secondary end point was the percentage of satisfaction of hair patient-reported outcome responders. Significantly higher proportions of patients taking deuruxolitinib met the primary end point (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary end points versus placebo, including satisfaction of hair patient-reported outcome (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth. [ABSTRACT FROM AUTHOR]

Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. To assess the efficacy and safety of apremilast 30 mg twice daily in patients with genital psoriasis. DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. Patients were randomized to apremilast (n = 143) or placebo (n = 146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P =.0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. Lack of active-comparator. Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis. [ABSTRACT FROM AUTHOR]

Background: The heterogeneous course of moderate-to-severe atopic dermatitis necessitates treatment flexibility.Objective: We evaluated the maintenance of abrocitinib-induced response with continuous abrocitinib treatment, dose reduction or withdrawal, and response to treatment reintroduction following flare (JAK1 Atopic Dermatitis Efficacy and Safety [JADE] REGIMEN: National Clinical Trial 03627767).Methods: Patients with moderate-to-severe atopic dermatitis responding to open-label abrocitinib 200 mg monotherapy for 12 weeks were randomly assigned in a 1:1:1 ratio to blinded abrocitinib (200 or 100 mg) or placebo for 40 weeks. Patients experiencing flare received rescue treatment (abrocitinib 200 mg plus topical therapy).Results: Of 1233 patients, 798 responders to induction (64.7%) were randomly assigned. The flare probability during maintenance was 18.9%, 42.6%, and 80.9% with abrocitinib 200 mg, abrocitinib 100 mg, and placebo, respectively. Among patients with flare in the abrocitinib 200 mg, abrocitinib 100 mg, and placebo groups, 36.6%, 58.8%, and 81.6% regained investigator global assessment 0/1 response, respectively, and 55.0%, 74.5%, and 91.8% regained eczema area and severity index response, respectively, with rescue treatment. During maintenance, 63.2% and 54.0% of patients receiving abrocitinib 200 and 100 mg, respectively, experienced adverse events.Limitations: The definition of protocol-defined flare was not established, limiting the generalizability of findings.Conclusion: Induction treatment with abrocitinib was effective; most responders continuing abrocitinib did not flare. Rescue treatment with abrocitinib plus topical therapy effectively recaptured response. [ABSTRACT FROM AUTHOR]

Background: Topical psoriasis treatment relies on a reactive rather than a long-term proactive approach to disease relapse.Objective: Assess long-term efficacy and safety of proactive psoriasis management with twice-weekly calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam.Methods: Phase III trial (NCT02899962) included a 4-week open-label lead-in phase (Cal/BD foam once daily) and a 52-week, randomized, double-blind, maintenance phase. A total of 545 patients achieved treatment success (physician's global assessment "clear"/"almost clear," ≥2-grade improvement from baseline) and were randomized to proactive management (Cal/BD foam; n = 272) or reactive management (vehicle foam; n = 273) twice-weekly, with rescue treatment of Cal/BD foam once daily for 4 weeks upon relapse. Primary endpoint was time to first relapse (physician's global assessment "mild" or higher).Results: A total of 251 randomized patients (46.1%) completed the trial. Median time to first relapse was 56 days (proactive) and 30 days (reactive). Patients in the proactive group had an additional 41 days in remission compared with the reactive group over 1 year (P < .001). Number of relapses per year of exposure was 3.1 (proactive) and 4.8 (reactive). Cal/BD foam was well tolerated.Limitations: Maintenance phase dropout rate (53.9%) was within the expected range but provides challenges in statistical analysis.Conclusion: Long-term proactive management with Cal/BD foam demonstrated superior efficacy vs reactive management. [ABSTRACT FROM AUTHOR]

Background: Many patients with psoriasis are bothered by symptoms in highly visible, pruritic areas, such as the scalp.Objective: To evaluate the efficacy and safety of apremilast for moderate to severe scalp psoriasis.Methods: This phase 3b, double-blind, placebo-controlled study randomized adults with moderate to severe scalp psoriasis who had inadequate response/intolerance to at least 1 topical scalp psoriasis therapy (NCT03123471). The primary endpoint was the proportion of patients who achieved Scalp Physician Global Assessment response, defined as score of 0 (clear) or 1 (almost clear), with at least a 2-point reduction, at week 16. Secondary endpoints included at least a 4-point improvement from baseline in Whole Body Itch and Scalp Itch Numeric Rating Scales (NRSs) and mean improvement in Dermatology Life Quality Index (DLQI) at week 16.Results: There were 303 randomized patients (placebo: n = 102; apremilast: n = 201). With apremilast, significantly more patients achieved Scalp Physician Global Assessment (43.3% vs 13.7%), Scalp Itch NRS (47.1% vs 21.1%), and Whole Body Itch NRS (45.5% vs 22.5%) response, and significantly greater DLQI improvement was observed versus placebo (-6.7 vs -3.8; all P < .0001). Common adverse events with apremilast were diarrhea (30.5%), nausea (21.5%), headache (12.0%), and vomiting (5.5%).Limitations: Patients with mild disease were not enrolled.Conclusion: Apremilast showed efficacy for the treatment of moderate to severe scalp psoriasis. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled studies of combination therapies in rosacea are limited.Objective: Evaluate the efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40-mg modified-release capsules (ie, 30-mg immediate-release and 10-mg delayed-release beads) (DMR) versus IVM and placebo for treatment of severe rosacea.Methods: This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA] score, 4) to receive either IVM and DMR (combination arm) or IVM and placebo (monotherapy).Results: A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (-80.3% vs -73.6% for monotherapy [P = .032]) and IGA score (P = .032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving an IGA score of 0 (11.9% vs 5.1% [P = .043]) and 100% lesion reduction (17.8% vs 7.2% [P = .006]) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index score, and ocular signs/symptoms and were well tolerated.Limitations: The duration of the study prevented evaluation of potential recurrences or further improvements.Conclusion: Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied.Objectives: Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne.Methods: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator's Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results.Results: In both studies, at week 12 the facial success rates according to the Investigator's Global Assessment and truncal Physician's Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P < .001) in favor of trifarotene when compared with the vehicle.Limitations: Adjunctive topical or systemic treatments were not studied.Conclusion: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne. [ABSTRACT FROM AUTHOR]

Molecular and cellular understanding of psoriasis pathogenesis has evolved considerably over the last 30 years beginning in the early 1980s when psoriasis was thought to be a skin disease driven by keratinocyte hyperproliferation. During the next 20 years, the role of the immune system and T-helper (Th) cells in psoriasis pathogenesis was recognized. The presence of the interleukin (IL)-12 cytokine in psoriatic lesions led to the postulate that psoriasis is mediated by Th1 cells. Recent evidence has revealed a role for Th17 cells, and other immune cells, as proximal regulators of psoriatic skin inflammation. IL-17A, the principal effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines, and other proinflammatory mediators thereby enabling IL-17A to bridge the innate and adaptive immune systems to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17A signaling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop. Several monoclonal antibodies that inhibit the IL-17 pathway are in clinical development. These agents exhibit promising clinical efficacy and tolerability profiles including immunohistochemical improvement in psoriatic plaques. Results from clinical trials with IL-17 pathway inhibitors are refining our understanding of psoriasis pathogenesis and may provide a new therapeutic approach for patients with moderate to severe psoriasis. [Copyright &y& Elsevier]

Background: Biologic therapies are used to treat moderate to severe psoriasis, but evidence from randomized, controlled studies is lacking regarding scalp-related effectiveness. Objective: To evaluate the efficacy and safety of etanercept for scalp symptoms (erythema, induration, scale, and percentage of scalp involvement) in patients with moderate to severe plaque psoriasis and scalp involvement. Methods: In this randomized, placebo-controlled study, adult patients with stable plaque psoriasis and significant scalp symptoms received etanercept 50 mg twice weekly (BIW) by subcutaneous injection (SC) for 12 weeks, followed by etanercept 50 mg once weekly (QW) and placebo QW (Group A, n = 62) or SC placebo BIW for 12 weeks, followed by etanercept 50 mg BIW for 12 weeks (Group B, n = 62). The primary end point was percentage change in Psoriasis Scalp Severity Index (PSSI) at week 12. Results: Demographics and disease characteristics were balanced: 56% men, 73% white, median age 41 years, median BMI 30.2 kg/m2. At week 12, mean PSSI improvement was 86.8% (standard deviation [SD], 18.0%) in Group A and 20.4% (SD, 39.3%) in Group B (P < .0001). At week 24, mean PSSI improvements were as follows: Group A, 90.6% (SD 13.1%); Group B, 79.1% (SD 33.6%). At week 12, 51 of 59 (86%) Group A patients and 7 of 61 (11%) Group B patients achieved PSSI 75 (P <.0001). Three patients (2.7%) reported 5 serious adverse events: cholecystitis/cholelithiasis, fall/rib fracture, and metastatic malignant melanoma. Limitations: The study was insufficiently powered to detect rare adverse events potentially associated with etanercept. Conclusions: Etanercept is an effective, well-tolerated treatment for plaque psoriasis involving the scalp. [Copyright &y& Elsevier]

Background: Alefacept is a T cell–modulating biologic therapy for psoriasis that could affect patients'' ability to mount immune responses. Objective: This open-label, phase IV, multicenter study assessed the ability of adults with chronic plaque psoriasis receiving alefacept to generate antibodies to a pneumococcal polysaccharide vaccine (PPV). Methods: Patients were treated with a standard 12-week course of alefacept and administered the 23-valent PPV at week 6. Antipneumococcal antibodies were measured at baseline and weeks 6, 9, 12, and 33. The primary end point was the percentage of patients with a 2-fold or greater increase from prevaccination (week 6) to 6 weeks postvaccination (week 12) in antibody titers to 2 or more of 5 designated PPV antigens. Results: Of 43 patients enrolled, 42 were included in the full analysis set, with 86% of patients exhibiting a 2-fold or greater increase and 57% of patients exhibiting a 4-fold or greater increase in antibody titers to 2 or more of 5 designated antigens from prevaccination to 6 weeks postvaccination. At 6 months postvaccination, 78% of patients had a 2-fold or greater increase and 47% of patients had a 4-fold or greater increase in antibody titers to 2 or more of the 5 designated antigens. There were statistically significant increases in mean antibody titers to all 23 antigens in PPV from prevaccination to 6 weeks postvaccination. Limitations: This was an open-label study with no comparator. Conclusions: Most patients mounted immune responses to PPV; increases in antibody titers in these patients were consistent with those seen in healthy individuals. [Copyright &y& Elsevier]

Background: The safety and efficacy of adalimumab in patients who have shown an unsatisfactory response to etanercept are unknown. Objective: We sought to evaluate the safety and efficacy of adalimumab in patients who failed to show a satisfactory response or lost their satisfactory response to etanercept. Methods: This multicenter study enrolled patients who either failed to reach a physician global assessment (PGA) score of 0 or 1 after 12 weeks of etanercept (group A; 50 patients) or who lost their PGA score of 0 or 1 at any time after etanercept dose decrease from 50 mg twice a week to 50 mg every week (group B; 35 patients). Patients received adalimumab 40 mg every other week without loading dose for 12 weeks followed by 40 mg every week for an additional 12 weeks if they did not reach a PGA score of 0 or 1. Results: After 12 weeks of adalimumab, 34.0% (n = 17; 95% confidence interval [CI] 20.4-47.6) and 31.4% (n = 11; 95% CI 15.2-47.6) of patients from groups A and B, respectively, reached a PGA score of 0 or 1. A total of 46.0% (n = 23; 95% CI 31.7-60.3) and 45.7% (n = 16; 95% CI 28.4-63.1) of patients from group A and B, respectively, achieved a PGA score of 0 or 1 after 24 weeks of adalimumab. Adalimumab was well tolerated and no serious adverse events were reported. Limitations: This was an open-label uncontrolled study. Conclusions: Adalimumab should be considered as an alternative in patients with psoriasis who have not shown an adequate response or who lost their response to etanercept after a dose decrease. [Copyright &y& Elsevier]

Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit–risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis. We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19). Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years). Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Background The optimal long-term dosing strategy for adalimumab (ADA) in hidradenitis suppurativa/acne inversa (HS) was evaluated by pooling the results of the PIONEER phase 3 trials and an open-label extension (OLE) study. Objective To assess the response to and tolerability of long-term administration of ADA in HS. Methods The durations of the PIONEER I/II periods A, B, and OLE were 12, 24, and 52 or more weeks, respectively. Patients who entered the OLE and received ADA (40 mg every week continuously) and responders plus partial responders (PRRs) were evaluated. Primary efficacy assessments included measurement of HS clinical response (HiSCR), lesion counts, skin pain, and Dermatology Life Quality Index (DLQI). Treatment-emergent adverse events were assessed. Results At week 12, 52.3% of those receiving ADA weekly and 73.0% of PRRs achieved HiSCR. Achievement of HiSCR was maintained through week 168 in 52.3% of patients who received ADA weekly and 57.1% of PRRs. Sustained improvement in lesion counts, skin pain, and DLQI score were also observed. The safety profile throughout the OLE was similar to the profiles observed in the PIONEER studies. Limitations The OLE was uncontrolled. Conclusion Continuous weekly dosing with ADA, 40 mg, is a reasonable treatment option for long-term control of moderate-to-severe HS. Graphical abstract [ABSTRACT FROM AUTHOR]

Background: The optimal long-term dosing strategy for adalimumab (ADA) in hidradenitis suppurativa/acne inversa (HS) was evaluated by pooling the results of the PIONEER phase 3 trials and an open-label extension (OLE) study.Objective: To assess the response to and tolerability of long-term administration of ADA in HS.Methods: The durations of the PIONEER I/II periods A, B, and OLE were 12, 24, and 52 or more weeks, respectively. Patients who entered the OLE and received ADA (40 mg every week continuously) and responders plus partial responders (PRRs) were evaluated. Primary efficacy assessments included measurement of HS clinical response (HiSCR), lesion counts, skin pain, and Dermatology Life Quality Index (DLQI). Treatment-emergent adverse events were assessed.Results: At week 12, 52.3% of those receiving ADA weekly and 73.0% of PRRs achieved HiSCR. Achievement of HiSCR was maintained through week 168 in 52.3% of patients who received ADA weekly and 57.1% of PRRs. Sustained improvement in lesion counts, skin pain, and DLQI score were also observed. The safety profile throughout the OLE was similar to the profiles observed in the PIONEER studies.Limitations: The OLE was uncontrolled.Conclusion: Continuous weekly dosing with ADA, 40 mg, is a reasonable treatment option for long-term control of moderate-to-severe HS. [ABSTRACT FROM AUTHOR]

Background: A new aqueous gel formulation of dapsone has been developed that allows clinically-effective doses of dapsone to be administered topically with minimal systemic absorption. Objectives: The goal of these studies was to evaluate the efficacy and safety of dapsone gel, 5% in the treatment of acne. Methods: Patients 12 years of age and older with acne vulgaris (N = 3010) participated in two identically-designed 12-week, randomized, double-blind studies of twice-daily monotherapy with dapsone gel, 5%, versus a vehicle gel. Results: Dapsone gel–treated patients achieved superior results in terms of the investigator''s global acne assessment (P < .001) and the mean percentage reduction in inflammatory, noninflammatory, and total lesion counts (all, P < .001) at week 12. Reductions in inflammatory lesion counts favoring dapsone gel over vehicle were apparent as early as 2 weeks and reached statistical significance by 4 weeks. No clinically significant changes in laboratory parameters, including hemoglobin, even among glucose-6-phosphate dehydrogenase–deficient patients, were observed. Adverse events were comparable between the treatment groups and rarely led to discontinuation. Limitations: Adjunctive topical treatments and their impact on acne were not studied in this trial. Conclusions: Dapsone gel, 5% appears to be an effective, safe, and well-tolerated treatment for acne vulgaris, with a rapid onset of action. [Copyright &y& Elsevier]