Outcomes of Down-Titration in Patients with Severe Scalp Alopecia Areata Initially Treated with Baricitinib 4-mg: Week 152 data from BRAVE-AA2.

BACKGROUND: Baricitinib, an oral selective Janus kinase inhibitor, is approved to treat adults with severe alopecia areata (AA). OBJECTIVE: To report the Week 152 efficacy results from the Phase 3 trial BRAVE-AA2 down-titration sub-study. METHODS: BRAVE-AA2 enrolled 546 adults with severe AA (Severity of Alopecia Tool [SALT] score ≥50). Baricitinib 4-mg treated patients achieving a clinical response (SALT score ≤20) at Week 52 were rerandomized 1:1 to stay on 4-mg or down-titrate to 2-mg. Last observation carried forward was used to impute missing or censored data. RESULTS: At Week 52, 86/234 (36.8%) baricitinib 4-mg treated patients were eligible for down-titration; 44 remained on 4-mg while 42 down-titrated to 2-mg. At Week 152, 39/44 (88.6%) 4-mg treated patients had maintained clinical response, compared to 24/41 (58.5%) down-titrated patients. Among down-titrated patients, loss of treatment benefit was less frequent in those with sustained response and SALT score ≤5 at Week 52. LIMITATIONS: Method and timing of down-titration were pre-specified in the protocol based on Week 52 responder status and not on other clinical factors. CONCLUSION: More than half of down-titrated patients maintained response. Sustained treatment response and/or near-total regrowth may be associated with a greater likelihood of response maintenance after down-titration.

When to expect scalp hair regrowth during treatment of severe alopecia areata with baricitinib: insights from trajectories analyses of patients enrolled in two phase III trials.

BACKGROUND: Baricitinib is approved for the treatment of adults with severe alopecia areata (AA). In the absence of robust data on the patterns of regrowth during treatment of severe AA, there is a gap in the knowledge regarding treatment expectations. OBJECTIVES: To examine whether different clinical response subgroups could be identified in baricitinib-treated patients with severe AA and factors that contribute to these subgroups. METHODS: The BRAVE-AA1 and BRAVE-AA2 phase III trials enrolled patients with severe AA [Severity of Alopecia Tool (SALT) score ≥ 50 (≥ 50% scalp hair loss)]. Patients randomized to baricitinib 4 mg or 2 mg retained their treatment allocation for 52 weeks. Based on patterns identified through growth mixture modelling (GMM), patients were categorized into responder subgroups according to when they first achieved ≥ 30% improvement from baseline in SALT score (SALT30). For each responder subgroup, trajectories of response (i.e. achievement of a SALT score ≤ 20, SALT score ≤ 10 and ≥ 50% change from baseline in SALT score) and baseline disease characteristics are reported. RESULTS: Respectively, 515 and 340 patients were randomized to once-daily baricitinib 4 mg and 2 mg at baseline; 69% and 51%, respectively, achieved SALT30 at least once by week 52. Based on GMM findings, we identified three responder subgroups: early (SALT30 by week 12), gradual (SALT30 after week 12-week 36) and late (SALT30 after week 36-week 52). The proportions of early, gradual and late responders and nonresponders were, respectively, 33%, 28%, 8% and 31% among patients treated with baricitinib 4 mg, and 20%, 23%, 9% and 49%, respectively, among those treated with baricitinib 2 mg. Early responders had a shorter trajectory to maximal clinical outcomes (e.g. > 78% achieved a SALT score ≤ 20 by week 36) vs. gradual or late responders. Early responders were more frequent among patients with baseline severe AA (SALT score 50 to < 95) vs. very severe AA (SALT score 95-100). Overall, responders (early to late) were more frequent in patients with short (< 4 years) episodes of hair loss. CONCLUSIONS: These analyses identified early, gradual and late responder subgroups for scalp hair regrowth in baricitinib-treated patients with severe AA, and that these subgroups are influenced by baseline characteristics. Findings from these analyses will help to inform treatment expectations for scalp hair regrowth.

Comparison of two-year treatment adherence, persistence, discontinuation, reinitiation, and switching between psoriasis patients treated with ixekizumab or secukinumab in real-world settings.

BACKGROUND: Real-world data on long-term treatment patterns associated with interleukin-17A inhibitors in plaque psoriasis are lacking. OBJECTIVE: To compare ixekizumab or secukinumab treatment patterns over a 24-month period among plaque psoriasis patients. METHODS: Adult patients with psoriasis who had 1 or more claims for ixekizumab or secukinumab between March 1, 2016, and October 31, 2019, and with 24 months of follow-up after starting treatment were identified from IBM MarketScan claims databases. Inverse probability of treatment weighting and multivariable models were employed to balance cohorts and estimate the risks of nonpersistence, discontinuation, and switching and odds of highly adherent treatment (proportion of days covered ≥ 80%). RESULTS: A total of 471 ixekizumab and 990 secukinumab users were included. Compared to secukinumab, ixekizumab use was associated with a 20% lower risk of nonpersistence (hazard ratio, 0.80; 95% CI, 0.70-0.92), a 17% lower risk of discontinuation (hazard ratio, 0.83; 95% CI, 0.72-0.96), and a 42% higher odds of being highly adherent to treatment (odds ratio, 1.42; 95% CI, 1.12-1.80). No difference in risk of switching was observed (hazard ratio, 0.83; 95% CI, 0.68-1.01). LIMITATIONS: Disease severity and clinical outcomes were unavailable. CONCLUSION: Over 24 months, ixekizumab users exhibited better persistence and adherence, and a lower risk of discontinuation than secukinumab users in real-world settings.

Long-Term Treatment Patterns Among Patients With Psoriasis Treated With Ixekizumab or Adalimumab: A Real-World Study.

BACKGROUND: There is a paucity of long-term real-world evidence comparing the effectiveness of ixekizumab (IXE) and adalimumab (ADA). We compared real-world treatment patterns of IXE-treated and ADA-treated patients with psoriasis over 24 months in the United States. METHODS: A retrospective observational study was conducted using IBM Watson Health MarketScan® databases. Adult patients with psoriasis having ≥1 claim for IXE or ADA from March 1, 2016 – October 31, 2019 were identified. Inverse probability of treatment weighting (IPTW) was used to address cohort imbalances. Cox proportional hazards models were used to estimate the risks of non-persistence, discontinuation, and switching. Logistic regression was used to estimate odds of high adherence. Persistence, adherence, discontinuation, reinitiation, and dosing and switching rates were also analyzed. RESULTS: The final cohorts comprised 475 IXE users and 3159 ADA users over 24 months. IXE users demonstrated higher adherence (36.3% vs 28.8%; P<0.001) and persistence rates (35.2% vs 28.8%; P=0.004), and a lower discontinuation rate (59.1% vs 65.3%; P=0.007) compared to ADA users. IXE users had a higher likelihood of being treatment-adherent compared to ADA users (OR=1.52, 95% CI: 1.24–1.87), a lower risk of non-persistence (HR=0.84, 95% CI: 0.75–0.95), and a lower risk of discontinuation (HR=0.83, 95% CI: 0.74–0.94), respectively. Switching rates were similar in both groups (31.2% vs 30.0%; P=0.608). CONCLUSION: IXE users had better treatment adherence and persistence, and a lower risk of discontinuation compared to ADA users over 24 months. There was no difference in the risk of switching between IXE and ADA. J Drugs Dermatol. 2022;21(4):399-407. doi:10.36849/JDD.6336.

Higher rates of skin clearance and efficacy in challenging body areas are associated with better health-related quality of life following ixekizumab maintenance treatment in pediatric patients with plaque psoriasis.

BACKGROUND/OBJECTIVES: Information is limited on the relationship between skin clearance, resolution of challenging body areas, and improvement of patient-reported outcomes (PROs) in pediatric psoriasis. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe psoriasis in patients aged 6 to <18 years. This study examines improvement in psoriasis clearance in challenging body areas in pediatric patients relative to health-related quality of life. METHODS: Data from the IXORA-PEDS trial (NCT03073200) were analyzed, and changes from baseline were measured for overall Psoriasis Area and Severity Index (PASI), static Physicians' Global Assessment of psoriasis (sPGA), Psoriasis Scalp Severity Index (PSSI), Palmoplantar Psoriasis Area and Severity Index (PPASI), and Nail Psoriasis Severity Index. Rates of Dermatology Life Quality Index (DLQI), or Children's DLQI (CDLQI), scores of 0 or 1 were evaluated using the Cochran-Armitage trend test. RESULTS: Higher rates of DLQI/CDLQI (0,1) scores were significantly associated with greater PASI and PSSI responses at both Week 12 and Week 48 (p < .0001). A significant association was also observed between DLQI/CDLQI (0,1) and sPGA scores (p < .0001). Significantly higher rates of DLQI/CDLQI (0,1) scores were achieved in patients with greater levels of palmoplantar clearance as measured by PPASI at Week 12 (p = .0139), but significance was not sustained at Week 48 (p = .0896). CONCLUSIONS: Greater skin clearance and scalp resolution are associated with better PROs over a short-term (12-week) and long-term (48-week) period. This demonstrates that greater improvement of skin clearance and scalp resolution may benefit quality of life in pediatric patients with psoriasis.

A proposed classification for follicular involvement by melanoma.

BACKGROUND: Folliculotropism in melanoma is poorly characterized and standard categorization for follicular involvement by melanoma is unavailable. We propose a logical categorization system. METHODS: We conducted a search of our archives over a 24-year period for cases mentioning the terms follicle, follicular, folliculotropic, folliculocentric and melanoma. RESULTS: We identified 90 cases of melanoma with involvement of the hair follicle. Distinct patterns were identified. The invasive patterns were primary follicular, folliculotropic and invasive arising from melanoma in situ (MIS) with extensive follicular involvement. Follicular involvement by MIS was either lentiginous, nested or a combination of both. A total of 29 invasive melanomas were identified. Of these 12 had invasive melanoma around the hair follicle, 2 were primary follicular melanomas, 7 showed folliculotropism and 3 were invasive melanomas arising from MIS around the follicle. Seventeen invasive melanomas had follicles only involved by MIS (9 nested, 6 nested and lentiginous and 2 lentiginous). A total of 61 cases of MIS with follicular involvement were identified; of these 33 were lentiginous, 10 nested and 18 both lentiginous and nested. CONCLUSION: We propose that the three distinct patterns of follicular involvement by invasive melanoma and the three distinct patterns of MIS will be valuable for logically categorizing involvement of the hair follicle by melanoma.

Sustained Improvements in Clinical and Patient-Reported Outcomes and Quality of Life Through 5 Years Among Ixekizumab-Treated Patients with Complete Clearance of Scalp Psoriasis by Week 60.

INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe plaque psoriasis. Since scalp psoriasis can be burdensome and challenging to treat with non-systemic therapies, this post hoc analysis focused on scalp psoriasis in patients with moderate-to-severe plaque psoriasis and baseline scalp involvement. The analysis considered a holistic concept of clearance through 5 years of ixekizumab treatment. METHODS: Ixekizumab-treated patients with baseline scalp involvement were pooled from three multicenter, randomized, double-blind, placebo-controlled, phase 3 trials (integrated UNCOVER-1/2 and UNCOVER-3). Analyses were performed on a subpopulation of patients who achieved complete resolution of scalp psoriasis at Week 60 (i.e., Week 60 Psoriasis Scalp Severity Index [PSSI-0] responders) and on the overall patient population (i.e., Week 60 PSSI-0 responders and non-responders), which was used as a reference. Clinical outcomes (PSSI), patient-reported outcomes (Itch Numeric Rating Scale [NRS] score, Skin Pain Visual Analogue Scale [VAS]), quality of life (Dermatology Life Quality Index [DLQI]), and concurrent outcomes were assessed from baseline through 5 years. Descriptive statistics of observed data were reported. RESULTS: After 60 weeks of ixekizumab treatment, 88.4% (UNCOVER-1/2) and 75.9% (UNCOVER-3) of patients with baseline scalp involvement achieved complete clearance (PSSI-0) of scalp psoriasis. Substantial improvements in the clinical outcomes (PSSI), patient-reported outcomes (Itch NRS, Skin Pain VAS), and quality of life (DLQI) were achieved by Week 60 and sustained through Week 264 in the Week 60 PSSI-0 responders and in the overall patient population. Additionally, a significant proportion of Week 60 PSSI-0 responders achieved concurrent complete scalp and skin clearance and quality of life improvement through 5 years. CONCLUSIONS: Continued treatment with ixekizumab provided long-term sustained scalp clearance over 5 years to patients with moderate-to-severe plaque psoriasis and baseline scalp involvement, and holistic improvements occurred across clinical outcomes, patient-reported outcomes, and quality of life. CLINICAL TRIAL NUMBERS: NCT01474512 (UNCOVER-1), NCT01597245 (UNCOVER-2), and NCT01646177 (UNCOVER-3).

Baricitinib Withdrawal and Retreatment in Patients With Severe Alopecia Areata: The BRAVE-AA1 Randomized Clinical Trial.

Importance: Baricitinib has demonstrated efficacy for treating severe alopecia areata in adults. There is currently limited information about the need for continuous therapy after achieving scalp hair regrowth. Objective: To report results from the randomized withdrawal period of the BRAVE-AA1 trial. Design, Setting, and Participants: BRAVE-AA1 was a randomized, placebo-controlled, phase 3 randomized clinical trial with a treatment withdrawal substudy that was conducted at 70 centers in 3 countries beginning in March 2019. It included 654 adults with severe alopecia areata (AA) (Severity of Alopecia Tool [SALT] score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Data were analyzed in August 2023. Intervention: At week 52, 154 patients who were responders (SALT score ≤20) were rerandomized 3:1 to continue to take their current dose of baricitinib or transition to placebo (randomized withdrawal). Responders randomized to placebo who experienced a loss of treatment benefit (>20-point worsening in SALT score) at any time after week 52 were retreated with their original baricitinib dose. Main Outcome and Measures: The proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment. The last observation carried forward was used to impute missing or censored data. Results: Of 654 patients who received treatment, the mean (SD) age was 37.1 (13.0) years, and there were 383 women (58.6%). At week 52, 10 of 39 responders taking baricitinib, 2 mg, and 30 of 115 responders taking baricitinib, 4 mg, were rerandomized to placebo. At 4 and 8 weeks of treatment withdrawal, 0% and 10% to 11% of patients, respectively, lost treatment benefit regardless of dose. At week 152, 80% of patients had lost benefit compared with 7% for those who continued baricitinib therapy for both dose groups. Within the follow-up observation periods, 5 of 8 patients taking 2 mg (63%) and 21 of 24 patients taking 4 mg (87.5%) recaptured a SALT score of 20 or less response after retreatment. Conclusions and Relevance: Severe AA is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe AA who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth. Trial Registration: ClinicalTrials.gov Identifier: NCT03570749.

Efficacy of Baricitinib in Patients with Various Degrees of Alopecia Areata Severity: Post-Hoc Analysis from BRAVE AA1 and BRAVE AA2.

BACKGROUND: Baricitinib, an oral selective JAK1/JAK2 inhibitor, is approved for the treatment of adults with severe alopecia areata (AA). OBJECTIVE: To evaluate differences in response up to week 52 among subgroups based on the baseline severity of AA assessed with the Severity of Alopecia Tool (SALT) score. METHODS: Data were pooled from BRAVE-AA1 and BRAVE-AA2, two randomized, placebo-controlled, phase 3 trials, which enrolled adults with a SALT score ≥ 50. Patients were subdivided by the degree of AA severity at baseline. RESULTS: Among the 855 patients treated with baricitinib 2 mg and 4 mg, improvements in scalp hair growth continued through to week 52. A superior response was observed in patients with a SALT score of 50-94 versus a score of 95-100. Patients on baricitinib 4 mg had a faster and higher response rate compared to baricitinib 2 mg. CONCLUSION: Across all degrees of severity for baricitinib 2 mg and 4 mg doses, the proportion of patients responding was yet to plateau up to week 52. Response to treatment was longer for patients with a baseline SALT score 95-100. Further studies are needed to analyze other parameters that may impact observed response rates.

Comparison of Real-World Costs, Healthcare Resource Utilization, and Comorbidity-Related Costs Between Ixekizumab and Secukinumab Among Biologic-Experienced Patients with Psoriasis Over 18 Months in the USA.

BACKGROUND AND OBJECTIVE: Data on real-world healthcare costs for ixekizumab (IXE) and secukinumab (SEC) in biologic-experienced patients with psoriasis are limited. This study compared real-world costs and healthcare resource utilization between IXE and SEC in biologic-experienced patients with psoriasis over an 18-month follow-up period in the USA. METHODS: Adult patients with a diagnosis of psoriasis between 1 March, 2015 and 31 October, 2019 were identified using health insurance claims data from IBM Watson Health MarketScan®. The index date was the date of the first IXE or SEC claim. Biologic-experienced patients with one or more pre-period claims for biologic drugs were identified. Inverse probability of treatment weighting was used to reduce cohort imbalances. All-cause and psoriasis-related direct healthcare costs along with index drug costs were estimated during the follow-up and reported as per patient per month. Discount factors published by the Institute for Clinical and Economic Review were applied to psoriasis-related biologics to adjust pharmacy costs. RESULTS: A total of 411 IXE and 780 SEC users were included. After weighting, all-cause inpatient admissions were similar between IXE (9.5%) and SEC users (10.3%). Weighted, mean ± standard deviation per patient per month all-cause healthcare costs were higher in IXE users ($6670 ± $2910) than in SEC users ($6239 ± $3903; p = 0.049). Psoriasis-related and monthly index drug costs were higher in IXE users ($5609 ± $2009; p < 0.001 and $4688 ± $1994; p < 0.001, respectively) than in SEC users ($5095 ± $2291 and $3853 ± $1977, respectively). After Institute for Clinical and Economic Review adjustment, mean per patient per month all-cause ($4363 ± $2576 vs $4398 ± $3517) and psoriasis-related costs ($3302 ± $1264 vs $3253 ± $1504) were similar between the groups. Institute for Clinical and Economic Review- and adherence-adjusted mean per patient per month index drug costs were similar between IXE and SEC users (p = 0.339). CONCLUSIONS: Institute for Clinical and Economic Review-adjusted all-cause and psoriasis-related costs were comparable between IXE and SEC users among biologic-experienced patients over an 18-month follow-up period.

Clinical Outcomes for Uptitration of Baricitinib Therapy in Patients With Severe Alopecia Areata: A Pooled Analysis of the BRAVE-AA1 and BRAVE-AA2 Trials.

Importance: Baricitinib is an oral selective Janus kinase 1/2 inhibitor that has achieved clinically meaningful outcomes for scalp, eyebrow, and eyelash hair regrowth in patients with severe alopecia areata (AA) at week 36 of treatment. Treatment with baricitinib, 4 mg, has resulted in higher response rates than baricitinib, 2 mg, at weeks 36 and 52. Objective: To determine the efficacy of uptitration to baricitinib, 4 mg, for 24 weeks in patients who had previously not responded to baricitinib, 2 mg (Severity of Alopecia Tool [SALT] score of >20). Design, Setting, and Participants: BRAVE-AA1 and BRAVE-AA2 are multicenter, placebo-controlled, phase 3 randomized clinical trials that were initiated on September 24, 2018, and July 8, 2019, respectively, with follow-up to 200 weeks (data cutoffs of November 11, 2021, and November 5, 2021, respectively). This pooled analysis reports long-term extension data up to week 76. At baseline, 1200 adult patients with severe AA (SALT score ≥50) were randomly assigned in a 3:2:2 ratio to receive baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Patients treated with baricitinib remained on the same treatment dose until week 52. Patients were considered nonresponders to baricitinib, 2 mg, if they had a SALT score greater than 20 after 52 weeks of therapy. Main Outcomes and Measures: The proportions of patients achieving a SALT score of 20 or lower and clinician-reported outcome for eyebrow hair loss and eyelash hair loss scores of 0 or 1 (full coverage or minimal gaps) with 2-point or higher improvements from baseline (among those with baseline scores ≥2 [significant gaps to no notable hair]) were analyzed through week 76. Results: At week 52, of the 340 patients (mean [SD] age, 38.4 [12.9] years; 212 [62.4%] female) treated with baricitinib, 2 mg, 212 (62.4%) had a SALT score higher than 20 and were uptitrated to baricitinib, 4 mg. Two-thirds of these patients (142 of 212 [67.0%]) had a baseline SALT score of 95 to 100, indicating very severe AA. At week 76, 55 of the 212 patients (25.9%) had achieved a SALT score of 20 or lower. During the same period, response rates for clinician-reported outcome scores of 0 or 1 increased from 19.3% (31 of 161 patients) to 37.9% (61 of 161 patients) for eyebrows and from 24.1% (33 of 137 patients) to 40.9% (56 of 137 patients) for eyelashes. Conclusions and Relevance: In this pooled analysis of the BRAVE-AA1 and BRAVE-AA2 trials, uptitration of baricitinib, 2 mg, to baricitinib, 4 mg, in those who did not respond to the 2-mg dose resulted in meaningful improvement of response rates over the subsequent 24 weeks for scalp, eyebrow, and eyelash hair loss. Trial Registration: ClinicalTrials.gov Identifiers: NCT03570749 and NCT03899259.

Healthcare Costs Among Patients with Psoriasis Treated with Ixekizumab Versus Secukinumab in Real-World Settings Over 24 Months.

OBJECTIVE: The aim of this study was to compare healthcare costs between ixekizumab (IXE)-treated and secukinumab (SEC)-treated patients with psoriasis over a 24-month follow-up period in the United States. METHODS: Patients with psoriasis diagnosis were identified from IBM Watson Health MarketScan® Research Databases; those with one or more claim for index drug (IXE or SEC) between March 1, 2016 and October 31, 2019 were included. Included patients were ≥ 18 years old and had continuous enrollment with medical and pharmacy benefits ≥ 6 months before and ≥ 24 months after index date. Patients were classified as IXE or SEC users based on drug received at index. Per patient per month (PPPM) all-cause, psoriasis-related, and index drug costs for IXE and SEC users were estimated over 24 months of follow-up. Institute for Clinical and Economic Review (ICER) discount factors were applied to adjust pharmacy costs. Index drug costs were additionally adjusted for adherence. Inverse probability of treatment weighting was used to address cohort imbalances. Chi-square/t tests were used to compare IXE versus SEC users; p value < 0.05 was considered statistically significant. RESULTS: Overall, 1461 patients (IXE users, n = 471; SEC users, n = 990) were included. IXE versus SEC users had higher weighted PPPM all-cause, psoriasis-related, and index drug costs (p ≤ 0.001). IXE versus SEC users had comparable ICER-adjusted mean PPPM all-cause costs (US$4172 ± 3349 vs US$3978 ± 2619; p = 0.227) and psoriasis-related costs (US$2950 ± 1332 vs US$2899 ± 1152; p = 0.447). After applying ICER and adherence adjustments, index drug costs were similar between IXE and SEC users (US$3794 ± 1822 vs US$3766 ± 1973; p = 0.795). CONCLUSIONS: All-cause and psoriasis-related costs were comparable between IXE and SEC users after ICER adjustments; index drug costs were similar after ICER and adherence adjustments.

Healthcare resource utilization and costs among patients with psoriasis treated with ixekizumab or adalimumab over 2 years of follow-up in real-world settings.

AIMS: To compare long-term healthcare resource utilization (HCRU) and costs among patients who initiated ixekizumab (IXE) or adalimumab (ADA) for treatment of psoriasis in the United States. METHODS: Adult patients with psoriasis who had ≥1 claim for IXE or ADA were identified from IBM MarketScan claims databases prior to the COVID-19 pandemic (1 March 2016-31 October 2019). The index date was the date of first claim for the index drug of interest. Inverse probability of treatment weighting was employed to balance treatment cohorts. All-cause and psoriasis-related HCRU and costs were examined for 24 months of follow-up. Costs were reported as per patient per month. Costs of psoriasis-related biologics were adjusted using published Institute for Clinical and Economic Review (ICER) discount factors. Index drug costs were adjusted for adherence and ICER discount rates. RESULTS: The analyses included 407 IXE and 2,702 ADA users. IXE users had significantly higher inpatient admission rate (all-cause HCRU: 14.9% vs. 11.0%; p =0.012) and greater mean length of stay per admission (days, 6.6 vs. 4.1; p =0.004) than ADA users. ICER-adjusted costs were significantly higher in IXE than ADA users (all-cause costs: $4,132 vs. $3,610; p <0.001; psoriasis-related costs $3,077 vs. $2,700; p <0.001). After adjusting for ICER and adherence, IXE and ADA drug costs were comparable ($3,636 vs. $3,677; p =0.714). LIMITATIONS: Study relied on administrative claims data, subjected to data coding limitations and data entry errors. Rebates, patient assistance programs, and commission to wholesalers are not always captured in claims. Adjustment made by ICER discount factors may lead to double-discounting if the discounts have been applied in claim payments. CONCLUSIONS: All-cause HCRU was higher in IXE than ADA users. Healthcare costs were also higher in IXE than ADA users after ICER adjustment, over 24 months. Cost differences were largely driven by higher treatment adherence associated with IXE. Index drug costs were comparable after ICER and adherence adjustments.

Long-term Efficacy and Safety of Up to 108 Weeks of Ixekizumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis: The IXORA-PEDS Randomized Clinical Trial.

Importance: About 1% of children and adolescents worldwide are affected by plaque psoriasis. Objective: To evaluate the long-term efficacy and safety of ixekizumab for pediatric patients with moderate to severe psoriasis. Design, Setting, and Participants: This multicenter randomized clinical trial (IXORA-PEDS) evaluated pediatric patients with plaque psoriasis. Participants were aged 6 years to younger than 18 years; had moderate to severe psoriasis, which was defined as Psoriasis Area and Severity Index (PASI) of 12 or higher, static Physician's Global Assessment (sPGA) score of 3 or higher, and psoriasis-affected body surface area of 10% or greater at screening and baseline; were candidates for phototherapy or systemic therapy; or had psoriasis that was not adequately controlled by topical therapies. Data analysis, which followed the intention-to-treat principle, was conducted from May to October 2021. Interventions: Pediatric patients were randomized 2:1 to receive either a weight-based dose of ixekizumab every 4 weeks or placebo. After a 12-week placebo-controlled period, patients entered a 48-week, open-label ixekizumab maintenance period (weeks 12-60), followed by an extension period that lasted through 108 weeks. A substudy evaluated the randomized withdrawal of ixekizumab after week 60. Main Outcomes and Measures: Efficacy outcomes at week 108 included the percentage of patients achieving 75% (PASI 75), 90% (PASI 90), or 100% (PASI 100) improvement from baseline; an sPGA score of 0 or 1 or score of 0; and improvement of 4 points or higher from baseline in the Itch Numeric Rating Scale. Safety outcomes included assessments of adverse events (AEs), including treatment-emergent AEs, serious AEs, and AEs of special interest, as well as improvement from baseline in a range of challenging body areas. Missing data for categorical outcomes were imputed using modified nonresponder imputation. Results: A total of 171 patients (mean [SD] age, 13.5 [3.04] years; 99 female children [57.9%]) were randomized to either ixekizumab (n = 115) or placebo (n = 56). Of 166 patients who entered the maintenance period, 139 (83.7%) completed week 108 of the trial. Primary and gated secondary end points were sustained through week 108, with patients achieving PASI 75 (91.7% [n = 86]), PASI 90 (79.0% [n = 74]), PASI 100 (55.1% [n = 52]), sPGA 0 or 1 (78.3% [n = 74]), and sPGA 0 (52.4% [n = 49]). Fifty-five patients (78.5%) reported an Itch Numeric Rating Scale improvement of 4 points or higher. In patients who received ixekizumab, at week 108, clearance of nail psoriasis was reported in 68.1% (n = 28), clearance of palmoplantar psoriasis was reported in 90.0% (n = 10), clearance of scalp psoriasis was reported in 76.2% (n = 83), and clearance of genital psoriasis was reported in 87.5% (n = 24). There were no new safety findings during weeks 48 to 108 of the trial, including no new cases of inflammatory bowel disease or candida infection. Conclusions and Relevance: Results of this study showed improvements across patient-reported outcomes and objective measures of complete skin clearance of psoriasis among pediatric patients who received ixekizumab, and these response rates were sustained through week 108 of the trial. Safety of ixekizumab was consistent with previously reported findings in this population and the known safety profile of this treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT03073200.

Subcutaneous myxopapillary ependymal rest: a potential sign of spinal dysraphism.

Subcutaneous myxopapillary ependymal rests are heterotopias of neuroglial tissue that present in the subcutaneous tissue of the sacrococcygeal region. We report a case which presented as a flesh-colored, pedunculated papule near the gluteal cleft. The presence of a congenital lesion near the midline of the spine should alert the clinician to the possibility of spinal dysraphism and necessitates imaging before biopsy. Subcutaneous myxopapillary rests are benign but must be distinguished from their histologic mimic, subcutaneous myxopapillary ependymomas, which are low-grade tumors with metastatic potential.

Comparison of Real-World Treatment Patterns Among Biologic-Experienced Patients with Psoriasis Treated with Ixekizumab or Secukinumab Over 18 Months.

INTRODUCTION: Real-world data comparing effectiveness of ixekizumab (IXE) and secukinumab (SEC) among biologic-experienced patients are limited. This study compared treatment patterns over 18 months among biologic-experienced patients with psoriasis receiving IXE or SEC in the USA. METHODS: A retrospective observational study using administrative claims data from IBM® Watson Health MarketScan® Research Databases included adult patients with ≥ 1 inpatient or ≥ 2 non-diagnostic (≥ 30 days apart) outpatient claim/s with diagnosis of psoriasis between March 1, 2015 and October 31, 2019, and ≥ 1 claim/s for index drugs, IXE or SEC, between March 1, 2016 and October 31, 2019. Patients had to have ≥ 1 claim/s for biologics indicated for psoriasis in the 6-month pre-period. During the 18-month follow-up, treatment adherence (proportion of days covered [PDC]), high adherence (PDC ≥ 80%), persistence, discontinuation, reinitiation, and switching were assessed. To address cohort imbalances, inverse probability of treatment weighting was employed. Logistic regression was used to estimate odds ratio for high adherence. Cox proportional hazard models were used to estimate hazard ratio for non-persistence, discontinuation, and switching. RESULTS: Overall, 411 IXE and 780 SEC users were included. After weighting, IXE users had significantly higher rate of high treatment adherence (42% vs. 35%, p = 0.019), higher persistence rate (44.9% vs. 36.9%, p = 0.007), lower discontinuation rate (48.4% vs. 56.0%, p = 0.012), and lower switching rate (26.6% vs. 34.0%, p = 0.009) compared with SEC users. After multivariable adjustment, compared with SEC, IXE use was associated with 36% higher odds of high treatment adherence (OR 1.36, 95% CI 1.05-1.74), 20% lower risk of treatment non-persistence (HR 0.80, 95% CI 0.68-0.93), 19% lower risk of discontinuation (HR 0.81, 95% CI 0.68-0.96), and 25% lower risk of switching (HR 0.75, 95% CI 0.60-0.93). CONCLUSION: This study suggests that IXE treatment is associated with significantly higher adherence rates and significantly lower non-persistence, discontinuation, and switching compared with SEC treatment.

Simple non-staining method to demonstrate urate crystals in formalin-fixed, paraffin-embedded skin biopsies.

BACKGROUND: Gouty tophi classically occur as nodules over joints and the helix. The ideal fixative for preservation of gout crystals has traditionally been alcohol because the crystals are formalin and water soluble. However, most biopsies are submitted in formalin fixative, which results in dissolution of urate crystals leaving behind a non-specific pale amorphous area. Although complex staining methods to show urate crystals in tissue have been described, the present study elucidates a simple non-staining method utilizing a thick unstained coverslipped microscopy slide that allows detection and confirmation of birefringence of urate crystals in formalin-fixed, paraffin-embedded tissue. METHODS: Twenty-nine cases of cutaneous gouty tophi were evaluated using a hematoxylin-eosin (H&E)-stained section, a 10-microm unstained coverslipped section and a 4-microm unstained coverslipped section. In all cases, the specimen was received and submitted in formalin. RESULTS: Polarizable crystals were not identified in any of the H&E sections. The use of the thicker unstained coverslipped section was more sensitive than the standard 4 microm section by recognizing the characteristic urate crystals in 48% and 38% of the cases, respectively. CONCLUSIONS: This inexpensive adjunctive tool can be used to document gout crystals in almost half of skin biopsies.

Cutaneous malignant peripheral nerve sheath tumors.

Cutaneous malignant peripheral nerve sheath tumors (MPNSTs) are rare entities compared with their deep soft tissue counterparts. We describe two cases of cutaneous MPNSTs. The first case, occurring in a 27-year-old woman with neurofibromatosis I, presented with recent growth of a pre-existing nodule on her back. A biopsy showed a densely cellular area within a conventional neurofibroma composed of atypical, hyperchromatic epithelioid and spindled cells with frequent mitotic figures (MFs). The second case presented in an 88-year-old man with no stigmata of neurofibromatosis as a rapidly growing subcutaneous tumor of the right calf. A biopsy showed a diffuse neurofibroma that abruptly transitioned to a densely cellular proliferation of hyperchromatic atypical spindled cells arranged in short fascicles with frequent MFs. The diagnosis of MPNST was rendered in both cases. MPNSTs of the dermis and subcutis are rare sarcomas. They can occur as sporadic tumors or in the setting of neurofibromatosis. They are often associated with pre-existing neurofibromas. Increase in size of pre-existing neurofibromas is an indication for biopsy. Recognition of the cellular atypia, increased cellularity and mitotic activity is key to the diagnosis.

A histologic review of 27 patients with lichen planopilaris.

BACKGROUND: Lichen planopilaris (LPP) is a potential trichologic emergency that can result in permanent scarring alopecia. Histopathology is a key component of the diagnostic work-up. OBJECTIVE: To identify the key histologic features that characterize LPP in order to facilitate diagnosis, ultimately leading to improved patient outcomes. METHODS: Scalp biopsy specimens from 27 confirmed cases of LPP were reviewed in a blinded fashion to determine diagnostically helpful histologic features. RESULTS: Absence of arrector pili muscles and sebaceous glands, a perivascular and perifollicular lymphocytic infiltrate in the reticular dermis and mucinous perifollicular fibroplasia within the upper dermis with absence of interfollicular mucin, and superficial perifollicular wedge-shaped scarring were characterizing features. LIMITATIONS: Sample size was limited, given that biopsy specimens were taken from lesions at varying stages of evolution and findings vary with disease stage. CONCLUSIONS: This study confirms many previously reported histologic features and highlights new characterizing features of mucinous perifollicular fibroplasia.