Impact of disease, musculoskeletal symptoms and disease control in the CorEvitas Psoriasis Registry.

BACKGROUND: Early identification, diagnosis and symptom control of psoriatic arthritis (PsA) in patients with psoriasis remain unmet medical needs. OBJECTIVES: To compare the impact of disease and other characteristics between patients with psoriasis who screened positive for PsA using the Psoriasis Epidemiology Screening Tool (PEST) (screen-positive group) and patients who (i) have PsA (PsA group) or (ii) screened negative for PsA (screen-negative group). Also, to determine the proportion of patients at a patient-acceptable symptom state (PASS) in the screen-positive and PsA groups. METHODS: This was a cross-sectional analysis of the CorEvitas Psoriasis Registry. We included a convenience sample of patients with psoriasis from the screen-positive and PsA groups who completed the Psoriatic Arthritis Impact of Disease-12 (PsAID12), and a comparator screen-negative group who did not complete the PsAID12. We report descriptive summaries of demographics, comorbidities, psoriasis characteristics, patient-reported outcome measures and the proportion of patients at PASS (i.e. PsAID12 ≤ 4). RESULTS: The screen-positive, PsA and screen-negative groups included 369, 70 and 4724 patients, respectively. The screen-positive and PsA groups had a similar impact of disease, demographics, comorbidities and psoriasis characteristics (d < 0.337). Mean PsAID12 scores were 3.1 (SD 2.3) and 3.7 (SD 2.6) in the screen-positive and PsA groups, respectively. Compared with patients who screened negative for PsA, patients who screened positive exhibited higher rates of selected known predictors of PsA such as older age, longer psoriasis duration, nail disease and inverse psoriasis. The proportion of patients at PASS was 56% and 67% for the PsA and screen-positive groups, respectively. CONCLUSIONS: The similar profiles between screen-positive and PsA groups, in comparison with the screen-negative group, support observations of possible underdiagnosis of PsA and the increased impact of disease, especially musculoskeletal disease, among patients who screen positive for PsA. The high percentage of patients not at an acceptable symptom state in the PsA and screen-positive groups highlights the need to optimize care in PsA.

Efficacy and safety of guselkumab in patients with active psoriatic arthritis who had inadequate efficacy and/or intolerance to one prior tumor necrosis factor inhibitor: study protocol for SOLSTICE, a phase 3B, multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients. METHODS: The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator's Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel-Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively. DISCUSSION: Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021.

Bimekizumab safety in moderate to severe plaque psoriasis: Rates of hepatic events and changes in liver parameters over 2 years in randomized phase 3/3b trials.

BACKGROUND: Patients with psoriasis are at increased risk of liver function abnormalities. OBJECTIVE: Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis. METHODS: Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). RESULTS: 2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline. LIMITATIONS: Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction. CONCLUSION: Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods.

Safety of Secukinumab from 1 Million Patient-Years of Exposure: Experience from Post-Marketing Setting and Clinical Trials.

INTRODUCTION: Secukinumab is an anti-interleukin (IL)-17A monoclonal antibody indicated for multiple immunological disorders. Here, we aim to summarize secukinumab safety in clinical trials (CTs) and post-marketing setting (PMS) until 25 June 2022. METHODS: Adverse events (AEs) were summarized with crude reporting rate (RR) per 100 patient-years (PY) in PMS for all reported indications and with exposure-adjusted incident rates (EAIR) per 100 PY in pooled 47 CTs for approved indications. RESULTS: Secukinumab exposure totaled 1,159,260 PY in PMS and 27,765 PY in CTs. AEs were mostly (> 80%) non-serious in PMS. EAIR for serious AEs was 7.0/100 PY. Nasopharyngitis (RR 0.59/100 PY, EAIR 16.08/100 PY) and pneumonia (RR 0.14/100 PY, EAIR 0.17/100 PY) were the most common infection and serious infection, respectively. Candida infections (RR 0.20/100 PY, EAIR 2.16/100 PY) were the most common fungal infections. Inflammatory bowel disease (IBD) was observed in PMS (0.14/100 PY) and CTs (0.26/100 PY). Most (76%) patients with prior IBD did not report IBD flare during CTs. PMS monitoring identified paradoxical skin reactions including dyshidrotic eczema (RR 0.006/100 PY) and pyoderma gangrenosum (RR 0.003/100 PY). CONCLUSION: Secukinumab safety profile with increased patient exposure remained favorable. Paradoxical skin reactions were identified in post-marketing monitoring.

Novel Clinical Applications of Topical Ruxolitinib: A Case Series.

Topical ruxolitinib, a potent Janus kinase (JAK) inhibitor, has shown significant efficacy in treating inflammatory skin conditions. While its use has already been established in atopic dermatitis and vitiligo, recent reports suggest its potential efficacy in treating other dermatoses. Specifically, topical ruxolitinib may be an effective treatment option for refractory dermatological conditions that are inflammation-driven with dysregulated activity of cytokines implicated in the JAK/STAT pathway. In this case series, we present four novel clinical applications of topical ruxolitinib in treatment-resistant dermatological conditions. These cases include pediatric lichen sclerosus et atrophicus, morphea, perioral dermatitis, and notalgia paresthetica. All four patients reported noticeable symptomatic improvement and a significant improvement in the condition of their skin lesions. Our results suggest that ruxolitinib cream can successfully manage these conditions and may serve as supporting evidence for its formal evaluation.   J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7696.

Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials.

BACKGROUND: We report long-term, end-of-study program safety outcomes from 25 randomized clinical trials (RCTs) in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) [including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)] who received ≥ 1 dose of Ixekizumab (IXE) over 5 years (PsO) or up to 3 years (PsA, axSpA). METHODS: This integrated safety analysis consists of data from patients who received any dose of IXE, across 25 RCTs (17 PsO, 4 PsA, 4 axSpA). Rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and selected adverse events (AEs) of interest were analyzed for all pooled studies by years of therapy and overall, through March 2022. Results were reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) overall and at successive year intervals. RESULTS: Six thousand eight hundred ninety two adult patients with PsO, 1401 with PsA, and 932 with axSpA (including AS and nr-axSpA), with a cumulative IXE exposure of 22,371.1 PY were included. The most commonly reported TEAE across indications was nasopharyngitis (IRs per 100 PY: 8.8 (PsO), 9.0 (PsA), 8.4 (axSpA)). SAEs were reported by 969 patients with PsO (IR 5.4), 134 patients with PsA (IR 6.0), and 101 patients with axSpA (IR 4.8). Forty-five deaths were reported (PsO, n = 36, IR 0.2; PsA, n = 6, IR 0.3; axSpA, n = 3, IR 0.1). TEAEs did not increase during IXE exposure: IRs per 100 PY, PsO: 88.9 to 63.2 (year 0-1 to 4-5), PsA: 87 to 67.3 (year 0-1 to 2-3), axSpA: 82.1 to 55.4 (year 0-1 to > = 2). IRs per 100 PY of discontinuation from IXE due to AE were 2.9 (PsO), 5.1 (PsA), and 3.1 (axSpA). IRs per 100 PY of injection site reactions were 5.9 (PsO), 11.6 (PsA) and 7.4 (axSpA); Candida: 1.9 (PsO), 2.0 (PsA), and 1.2 (axSpA); depression, major adverse cerebro-cardiovascular events and malignancies: ≤ 1.6 across all indications. Adjudicated IRs per 100 PY of inflammatory bowel disease were ≤ 0.8 across indications (0.1 [PsO]; 0.1 [PsA]; 0.8 [axSpA]). CONCLUSIONS: In this integrated safety analysis, consisting of over 22,000 PY of exposure, the long-term safety profile of IXE was found to be consistent with previous, earlier reports, with no new safety signals identified. TRIAL REGISTRATION: NCT registration numbers for RCTs included in this integrated analysis can be found in Additional File 1.

Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL.

OBJECTIVES: To assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors. METHODS: Patients completing the 16-week phase III double-blind, placebo-controlled BE COMPLETE (NCT03896581) study entered the open-label extension, BE VITAL (NCT04009499). All patients in BE VITAL received 160 mg bimekizumab every 4 weeks. Safety and efficacy are reported to week 52. RESULTS: A total of 347/400 (86.8%) patients completed week 52. To week 52, the exposure-adjusted incidence rate/100 patient-years for ≥1 treatment-emergent adverse event (TEAE) was 126.0, and was 7.0 for serious TEAEs. The most frequent TEAEs were SARS-CoV-2 (COVID-19), oral candidiasis, nasopharyngitis and urinary tract infection. All fungal infections were mild or moderate in severity and localised; two patients discontinued the study due to oral candidiasis. No cases of active tuberculosis, uveitis or inflammatory bowel disease were reported. One sudden death occurred. Sustained efficacy was observed with bimekizumab from week 16 to |52 across clinical and patient-reported outcomes. At week 52, 51.7% bimekizumab-randomised and 40.6% placebo/bimekizumab patients (receiving bimekizumab from week 16 to 52) had ≥50% improvement in the American College of Rheumatology criteria. Complete skin clearance (Psoriasis Area and Severity Index 100) was achieved by 65.9% bimekizumab and 60.2% placebo/bimekizumab patients at week 52. Minimal disease activity was achieved by 47.2% bimekizumab and 33.1% placebo/bimekizumab patients at week 52. CONCLUSIONS: Bimekizumab demonstrated a safety profile consistent with previous reports; no new safety signals were identified. Sustained efficacy was observed from week 16 to 52.

Atopic Dermatitis as a Paradoxical Reaction to Secukinumab in a Patient With Plaque Psoriasis.

Paradoxical reactions to biologic agents used in the treatment of psoriasis are rare but have been reported with tumor necrosis factor (TNF) blockers and, more recently, with interleukin (IL)-17A inhibitors. Secukinumab, an IL-17A inhibitor, is an effective treatment for moderate-to-severe plaque psoriasis but has been implicated in the development or exacerbation of eczematous-like reactions in rare cases. We present a patient with a history of plaque psoriasis who developed an eczematous eruption after four months of secukinumab therapy, necessitating systemic intervention for adequate control. Five months after a loading dose of dupilumab, the patient appeared in the clinic with the return of classic, thick psoriatic plaques, affecting 15% BSA. The patient declined further treatment and was subsequently lost to follow-up despite multiple attempts to contact her. This case adds to the limited, but growing body of knowledge on IL-17 blocker-induced eczematous reactions and underscores the need for careful monitoring and prompt recognition of this adverse event in patients receiving this class of drugs. J Drugs Dermatol. 2024;23(2):97-99.     doi:10.36849/JDD.7639  .

A New Tool to Improve Communication Between Hidradenitis Suppurativa Patients and Health Care Providers.

BACKGROUND: Hidradenitis suppurativa (HS) patients tend to experience diagnosis delay, misdiagnosis, and embarrassment due to their condition. To address these issues, the International Dermatology Outcome Measure (IDEOM) HS Workgroup collaborated with patients to modify an existing Novartis questionnaire to better suit the needs of HS patients. This quality improvement project aimed to use the resulting Shine a Light on HS as Modified by the IDEOM HS Workgroup Questionnaire to enhance communication between HS patients and providers, improve clinical experience for HS patients, and gather relevant demographic data. METHOD: Patients with HS presenting to Mount Sinai Union Square over a 9-month long period were invited to complete the Shine a Light on HS as Modified by the IDEOM HS Workgroup Questionnaire before seeing their providers. After the visit, patients rated their overall clinical experience and the helpfulness of the survey on a 5-point scale. RESULTS: The analysis cohort (n=30) consisted of a racially and ethnically diverse patient population. On a scale of 0-4, the mean helpfulness rating was 3.1 (SD=1), and the mean clinical experience rating was 3.5 (SD=0.78). There was a positive correlation between survey helpfulness and overall clinical experience and a moderately strong relationship by linear regression analysis (r=0.73, R2=0.53). 80% reported frequent flares, 54% reported >10 years of symptoms, and the most commonly affected areas were the axillae, gluteal cleft, groin, and inguinocrural folds. The mean pain rating was 8 out of 10 (SD=2.55, Var=6.5). The majority of patients reported scars, tunnels, open wounds, ER/Urgent Care visits, inflammatory skin symptoms, and systemic symptoms. 39% had a positive HS family history. Biologics were the least common previous treatment reported (43%). Emotional burden was reported by nearly all patients, and comorbidities included depression, heart disease, arthritis, polycystic ovary syndrome (PCOS), diabetes, and irritable bowel disease (IBD). CONCLUSION: The Shine a Light on HS as Modified by the IDEOM HS Workgroup Questionnaire was successful in improving HS patient-provider conversations, enhancing the overall clinical experience for HS patients, and collecting insightful demographic data. Healthcare providers should consider incorporating the questionnaire as part of their routine care for HS to enhance clinical discussion and improve outcomes for patients. J Drugs Dermatol. 2024;23(2):105-109.   doi:10.36849/JDD.7624.

Patient-Reported Outcome Measures for Health-Related Quality of Life in Patients With Psoriasis: A Systematic Review.

Importance: Multiple patient-reported outcome measures (PROMs) for health-related quality of life (HRQL) exist for patients with psoriasis. Evidence for the content validity and other measurement properties of these PROMs is critical to determine which HRQL PROMs could be recommended for use. Objective: To systematically review the validity of HRQL-focused PROMs used in patients with psoriasis. Evidence Review: Using PubMed and Embase, full-text articles published in English or Spanish on development or validation studies for psoriasis-specific, dermatology-specific, or generic HRQL PROMs were included. Development studies included original development studies, even if not studied in psoriasis patients per Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations. If a study included multiple diagnoses, more than 50% of patients had to have psoriasis or psoriasis-specific subgroup analyses available. Data extraction and analysis followed the COSMIN guidelines. Two independent reviewers extracted and analyzed the data, including PROM characteristics, quality of measurement properties (structural validity, internal consistency, cross-cultural validity, reliability, measurement error, criterion validity, construct validity, and responsiveness), and level of evidence. PROMs were classified into 3 levels of recommendations: (1) PROM recommended for use; (2) PROM requires further validation; and (3) PROM not recommended for use. Findings: Overall, 97 articles were identified for extraction. This included 19 psoriasis-specific, 8 skin-specific, and 6 generic PROMs. According to COSMIN standards, most measures identified received a B recommendation for use, indicating their potential but requiring further validation. Only the Rasch reduced version of the Impact of Psoriasis Questionnaire (IPSO-11 Rasch) received an A recommendation for use given that it had sufficient content validity, structural validity, and internal consistency. Conclusions and Relevance: This study identified a significant lack of information concerning the quality of HRQL measures in psoriasis. This gap in knowledge can be attributed to the fact that traditional measures were developed using validation criteria that differ from the current standards in use. Consequently, additional validation studies in accordance with contemporary standards will be useful in aiding researchers and clinicians in determining the most suitable measure for assessing HRQL in patients with psoriasis.

Earlier clinical response predicts low rates of radiographic progression in biologic-naïve patients with active psoriatic arthritis receiving guselkumab treatment.

OBJECTIVE: Assess relationship between earlier clinical improvement and radiographic progression (RP) over 2 years in guselkumab-treated patients with active psoriatic arthritis (PsA). METHOD: Post hoc analyses combined data from DISCOVER-2 biologic-naïve adults with active PsA randomized to either guselkumab 100 mg every 4 weeks (Q4W) or guselkumab at W0, W4, then Q8W. Correlations (Spearman's coefficient) between baseline disease parameters and total PsA-modified van der Heijde-Sharp (vdH-S) score were examined. Repeated-measures mixed models, adjusted for known RP risk factors, assessed the relationship between Disease Activity Index in PsA (DAPSA) improvement, DAPSA improvement exceeding the median or the minimal clinically important difference (MCID), or DAPSA low disease activity (LDA) at W8 and RP rate, assessed by change from baseline in vdH-S score through W100. RESULTS: Baseline age, PsA duration, CRP level, and swollen joint count, but not psoriasis duration/severity, weakly correlated with baseline vdH-S score. Elevated baseline CRP (parameter estimate [ß] = 0.17-0.18, p < 0.03) and vdH-S score (ß = 0.02, p < 0.0001) significantly associated with greater RP through W100. Greater improvement in DAPSA (ß = -0.03, p = 0.0096), achievement of DAPSA improvement > median (least squares mean [LSM] difference: -0.66, p = 0.0405) or > MCID (-0.67, p = 0.0610), or DAPSA LDA (-1.44, p = 0.0151) by W8 with guselkumab significantly associated with less RP through W100. The effect of W8 DAPSA LDA on future RP was strengthened over time among achievers vs. non-achievers (LSM difference enhanced from -1.05 [p = 0.0267] at W52 to -1.84 [p = 0.0154] at W100). CONCLUSIONS: In guselkumab-treated patients with active PsA, earlier improvement in joint symptoms significantly associated with lower RP rates through 2 years, indicating blockade of the IL-23 pathway may modify long-term disease course and prevent further joint damage. Key Points • Greater improvement in DAPSA at Week 8 of guselkumab treatment was significantly associated with less progression of structural joint damage at 2 years in patients with active psoriatic arthritis (PsA). • Early control of peripheral joint disease activity with blockade of the IL-23 pathway may modify long-term PsA trajectory and prevent further joint damage.

A clinical review of structural damage in psoriatic arthritis for dermatologists: From pathogenesis to ongoing controversies.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that often goes unrecognized in patients with psoriasis. As a result, patients may develop significant structural damage before diagnosis and initiation of adequate treatment. Dermatologists are in an unique position to identify early signs and symptoms of PsA. Here, we briefly review the pathogenesis of PsA, differences in PsA presentation within real-world dermatology practice versus rheumatology clinical trials, and imaging modalities that can be used to assess structural damage. We then discuss several ongoing controversies related to prediction, assessment, and treatment of PsA-related structural damage. Debated questions include the following: (1) Does subclinical enthesitis predict progression from psoriasis to PsA?, (2) Does methotrexate inhibit progression of structural damage?, (3) Does structural damage correlate with clinical disease activity?, and (4) Can progression from psoriasis to PsA be prevented? Evidence presented herein suggests that dermatologists, together with rheumatologists, can play important roles in the early diagnosis and treatment of PsA, thereby potentially preventing irreversible structural damage.

Tape strips detect molecular alterations and cutaneous biomarkers in skin of patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) has a high unmet need for better treatments. Biopsies are considered the gold standard for studying molecular alterations in skin. A reproducible, minimally invasive approach is needed for longitudinal monitoring in trials and in pediatric populations. OBJECTIVE: To determine whether skin tape strips can detect molecular alterations in HS and identify biomarkers of disease activity. METHODS: We performed RNA sequencing on tape strips collected from lesional and healthy-appearing (nonlesional) HS skin (n = 22) and healthy controls (n = 21). We correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies. RESULTS: Tape strips detected upregulation of known HS biomarkers (eg, Interleukin[IL]-17A) in nonlesional and/or lesional skin and also identified novel clinically actionable targets, including OX40 and JAK3. The expression of Th17 and tumor necrosis factor-α pathways were highly correlated between tape strips and biopsies. HS clinical severity was significantly associated with expression of biomarkers (eg tumor necrosis factor-α , IL-17 A/F, OX40, JAK1-3, IL-4R) in HS lesional and/or nonlesional skin. LIMITATIONS: Sample size. Tape stripping is limited in depth. CONCLUSION: This study validates tape strips as a minimally-invasive approach to identify cutaneous biomarkers in HS. This provides a novel avenue for monitoring treatment efficacy and a potential step toward individualized therapy in HS.

International Dermatology Outcome Measures (IDEOM) - Report from the 2022 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) is a non-profit organization dedicated to the advancement of evidence-based, consensus-driven outcome measures in dermatological diseases. Researchers and stakeholders from various backgrounds collaborate to develop these objective benchmark metrics to further advance treatment and management of dermatological conditions. SUMMARY: The 2022 IDEOM Annual Meeting was held on June 17-18, 2022. Leaders and stakeholders from the hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, cutaneous lymphoma, and psoriatic disease workgroups discussed the progress of their respective outcome-measures research. This report summarizes each workgroup's updates from 2022 and their next steps as established during the 2022 IDEOM Annual Meeting. J Drugs Dermatol. 2023;22(12):1153-1159 doi:10.36849/JDD.7615.

A Case Series of Patients With Eczematous Eruptions Following IL-17 Inhibitor Treatment for Psoriasis Vulgaris.

Psoriasis vulgaris and eczema are characterized by an imbalance in the Th1 and Th2 immune response and distinct cytokine profiles, where Th1 is more prominent in psoriasis and Th2 is more prominent in eczema. A common treatment for psoriasis is anti-IL-17 therapy, in which inhibition of IL-17 cytokines and the Th1/Th17 immune response may cause a paradoxical shift favoring the Th2 immune response and an eczematous phenotype. Our case series presents three patients who developed a cutaneous eczematous eruption 8-12 weeks following treatment of psoriasis with an IL-17 inhibitor (secukinumab, ixekizumab, or brodalumab) suggesting this phenomenon of shifting cytokine levels away from the phenotype of psoriasis toward the opposing disease. J Drugs Dermatol. 2023;22(12):1225-1227. doi:10.36849/JDD.7388.

IL4Rα and IL17A Blockade Rescue Autoinflammation in SOCS1 Haploinsufficiency.

By inhibition of JAK-STAT signaling, SOCS1 acts as a master regulator of the cytokine response across numerous tissue types and cytokine pathways. Haploinsufficiency of SOCS1 has recently emerged as a monogenic immunodysregulatory disease with marked clinical variability. Here, we describe a patient with severe dermatitis, recurrent skin infections, and psoriatic arthritis that harbors a novel heterozygous mutation in SOCS1. The variant, c.202_203delAC, generates a frameshift in SOCS1, p.Thr68fsAla*49, which leads to complete loss of protein expression. Unlike WT SOCS1, Thr68fs SOCS1 fails to inhibit JAK-STAT signaling when expressed in vitro. The peripheral immune signature from this patient was marked by a redistribution of monocyte sub-populations and hyper-responsiveness to multiple cytokines. Despite this broad hyper-response across multiple cytokine pathways in SOCS1 haploinsufficiency, the patient's clinical disease was markedly responsive to targeted IL4Rα- and IL17-blocking therapy. In accordance, the mutant allele was unable to regulate IL4Rα signaling. Further, patient cells were unresponsive to IL4/IL13 while on monoclonal antibody therapy. Together, this study reports a novel SOCS1 mutation and suggests that IL4Rα blockade may serve as an unexpected, but fruitful therapeutic target for some patients with SOCS1 haploinsufficiency.

Successful Treatment of Lichen Planus With Oral Upadacitinib.

Lichen planus is an auto-inflammatory skin disorder marked by intensely pruritic, violaceous papules that commonly affect the extremities of middle-aged adults.1 There are several treatment options available, but alternative therapies to target disease refractory to standard interventions remain necessary. Though they have not been FDA-approved for lichen planus, Janus kinase (JAK) inhibitors have demonstrated significant potential as a therapeutic intervention across an array of dermatoses. Herein, we present a case of refractory, biopsy-proven lichen planus successfully treated with the oral JAK1 inhibitor, upadacitinib. J Drugs Dermatol. 2023;22(10):1058-1060     doi:10.36849/JDD.7272.

Prevalence of Musculoskeletal Symptoms in Patients with Psoriasis and Predictors Associated with the Development of Psoriatic Arthritis: Retrospective Analysis of a US Claims Database.

INTRODUCTION: Psoriasis (PsO) is associated with the development of psoriatic arthritis (PsA). Patients with PsO often experience pre-PsA musculoskeletal (MSK) symptoms, leading to potential structural damage and substantial disease burden with impact on function. The objective of this study is to describe prevalence rates and evidence of MSK symptoms, including incidence of comorbid PsA diagnosis, in patients newly diagnosed with PsO and identify factors associated with PsA diagnosis. METHODS: This retrospective analysis included administrative claims from the Optum Research Database for adult patients with a new PsO diagnosis between January 2008 and February 2019. Eligible patients had ≥ 2 claims for PsO on unique dates, were aged ≥ 18 years at the date of the first claim with a diagnosis of PsO (index date), and had continuous enrollment with medical and pharmacy coverage for 12 months before (baseline period) and ≥ 12 months following the index date. Primary outcomes were incidence of comorbid PsA diagnosis, prevalence of MSK symptoms other than PsA, and evidence of MSK symptoms collected at baseline and assessed in 12-month intervals through 60 months. RESULTS: Of the 116,203 patients with newly diagnosed PsO, 110,118 were without baseline comorbid PsA. High prevalence rates of MSK symptoms among patients with only PsO were seen at baseline (47.1%), 12 months (48.2%), and 60 months (82.1%). Patient age, baseline MSK symptoms, and baseline MSK symptom-related healthcare utilization were associated with increased hazard of a PsA diagnosis. CONCLUSION: Increased prevalence rates of MSK symptoms and burden are experienced by patients newly diagnosed with PsO through 60 months of follow-up. Several baseline factors were associated with increased risk of PsA diagnosis.

A Study to Look at Symptoms of Muscles, Joints, and Bones in Patients with Psoriasis and Whether They Can Predict a Diagnosis of Psoriatic ArthritisPsoriasis is an inflammatory skin disease that results in areas of significant itchiness, pain, and scaling, and ultimately decreases patient quality of life. Psoriasis affects approximately 2­4% of the general US population and 1.3­2.2% of the UK population. Some patients with psoriasis may experience musculoskeletal symptoms and may go on to develop psoriatic arthritis. The goal of this study was to determine the frequency of patients with psoriasis who experienced complaints of musculoskeletal pain prior to and/or following their psoriasis diagnosis, and whether these were associated with further probability of developing psoriatic arthritis.Using a large US-based database with data from approximately 115,000 patients with newly diagnosed psoriasis, we determined the percentage of newly diagnosed psoriasis patients with existing musculoskeletal pain complaints within 12 months of their initial diagnosis. We found that 47% of newly diagnosed patients had previous musculoskeletal pain complaints, with joint pain, back pain, and overall fatigue representing the most common forms. Notably, psoriasis patients with previous joint pain were approximately 50% more likely to develop psoriatic arthritis compared with patients with no previous joint pain. Furthermore, patients with previous other forms of arthritis were nearly twice as likely to develop psoriatic arthritis.This study provides additional support that existing musculoskeletal pain in patients with newly diagnosed psoriasis may predict the potential future onset of psoriatic arthritis. These findings will help guide primary care physicians, dermatologists, and rheumatologists in understanding the importance of earlier detection of psoriatic arthritis to provide more appropriate care.