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Introduction: Poor persistence to biologics can result in suboptimal health outcomes and increased economic burden for chronic conditions, including psoriasis (PsO). In Japan, studies evaluating factors responsible for biologic treatment persistence in patients with PsO are limited. We assessed biologic treatment persistence (median treatment duration and overall treatment survival) and associated factors in patients with PsO in a real-world setting. Methods: This retrospective analysis of insurance claims records from the Japan Medical Data Center (JMDC) database included patients with PsO [International Classification of Diseases (ICD) code: L40.x] ≥ 18 years of age who had received biologic treatment. Treatment persistence was analyzed using data from 2016 to 2020 by biologic class and by individual biologics (infliximab, adalimumab, ustekinumab, guselkumab, secukinumab, ixekizumab, and brodalumab) in bio-naïve (who initiate first biologic at index) and bio-experienced patients. Kaplan–Meier survival (treatment persistence), and multivariate Cox proportional hazard regression (predictive factors) analyses were used. Results: Overall, 1528 patients with PsO were included (mean age 47.4 years). Infliximab had the longest median treatment duration (33.6 months), while brodalumab had the shortest (9.7 months) among biologics evaluated. Of the biologics evaluated, 1-year treatment survival was highest with guselkumab (83%), and lowest with brodalumab (45%). Bio-experienced patients showed slightly longer median treatment duration than bio-naïve patients (22.8 versus 18.1 months). Factors predictive of treatment persistence were sex [male; hazard ratio (HR) 0.84, p = 0.016] and specific PsO diagnostic codes, such as L40.0 (PsO vulgaris; HR 0.69; p = 0.006), L40.1 (generalized pustular PsO; HR 0.75; p = 0.034), and L40.9 (PsO unspecified; HR 0.72; p = 0.001). Meanwhile, age and Charlson Comorbidity Index score were significantly associated with adalimumab and infliximab treatment persistence, respectively. Conclusion: Among biologics evaluated, infliximab had the longest median treatment duration, and guselkumab had the highest 1-year treatment survival. Sex and specific PsO diagnostic codes influenced overall treatment persistence. These findings could inform long-term treatment plans for PsO in real-world clinical settings. [ABSTRACT FROM AUTHOR]

Introduction: With newer biologics, the achievement of complete skin clearance has become an attainable treatment goal for patients with plaque psoriasis. We evaluate how improvements in Psoriasis Area and Severity Index (PASI) responses, particularly at incremental improvements approaching complete skin clearance (PASI 100), translate into improvements in health-related quality of life (HRQoL) and patient-perceived symptoms. Methods: Data from the BE RADIANT phase 3b trial (NCT03536884) and its open-label extension (OLE), pooled across all study visits and treatments over 16 weeks (randomised patients) and 2 years (patients entering the OLE), were analysed using mixed-effects logistic regression models. Proportions of patients achieving a Dermatology Life Quality Index (DLQI) of 0/1, DLQI item scores of 0, and Psoriasis Symptoms and Impacts Measure (P-SIM) item scores of 0 for itching, scaling, and skin pain at specific PASI improvement levels were estimated. Results: Seven hundred and forty-three patients were randomised to treatment; 654 entered the OLE. Using 16-week pooled data, there were incremental improvements in the proportions of patients estimated by our model to achieve DLQI 0/1 with PASI 100 compared with 95% (PASI = 95%) and 90% (PASI = 90%) improvements in PASI (93.0%, 89.3%, and 83.8% achieving DLQI 0/1, respectively). Estimated proportions achieving DLQI item scores of 0 had the greatest increases at higher PASI improvement levels for Items 1 (itchy, sore, painful, or stinging skin), 2 (embarrassment), and 4 (choice of clothing). Estimated proportions of patients achieving P-SIM = 0 were also higher for PASI 100 (itching: 61.7%; scaling: 82.2%; skin pain: 96.9%) than for PASI = 95% (50.8%; 72.3%; 95.7%) and PASI = 90% (39.8%; 59.5%; 94.0%). Similar benefits of incremental PASI improvements were estimated using 2-year data. Conclusions: Complete skin clearance translated into the greatest benefits to HRQoL and patient-perceived symptoms, over and above skin clearance between 90% and 100%, highlighting the importance of targeting PASI 100 as a treatment outcome for patients with psoriasis. Trial Registration Number: NCT03536884. 2APgg6-p_grKtG7KkQSkCG Complete skin clearance is associated with the greatest benefits to health-related quality of life and perceived symptoms for patients with psoriasis: KeyResults and Conclusions (MP4 72828 kb) [ABSTRACT FROM AUTHOR]

Introduction: The interleukin-23p19 subunit inhibitor, guselkumab, has demonstrated improvements in clinical and patient-reported outcome (PRO) measures in patients with moderate-to-severe psoriasis. Understanding the relationship among clinical response, PRO measures and baseline characteristics could help clinicians individualize treatment plans. The objective of this analysis was to examine changes in signs, symptoms and quality-of-life (QoL) PRO measures in patients who maintained complete skin clearance through ≥ 3 years in the phase 3 VOYAGE 1 trial. Methods: A descriptive post hoc analysis of data from VOYAGE 1 was conducted to compare baseline characteristics of patients who maintained complete skin clearance (Psoriasis Area and Severity Index [PASI] = 0 for ≥ 156 consecutive weeks) versus patients who did not. Mean scores for individual domains of the Dermatology Life Quality Index (DLQI) and Psoriasis Symptom and Sign Diary (PSSD) were evaluated in patients who maintained complete skin clearance, and baseline characteristics of patients who achieved PRO scores of DLQI = 0/1 and PSSD = 0 were compared with those who did not. Results: Of the 329 patients included in this post hoc analysis, 73 (22.2%) maintained PASI = 0 for ≥ 156 weeks. This group had a numerically lower proportion of patients at baseline with obesity, depression or previous biologic treatment and a higher proportion who had never smoked. Patients who maintained PASI = 0 generally achieved positive DLQI and PSSD outcomes, though some impact of residual disease was observed, largely related to the DLQI "Symptoms and feelings" sub-scale and PSSD components "Dryness," "Redness" and "Itch." Patients reporting continued disease impact (despite sustaining PASI = 0) had greater disease severity at baseline versus those achieving DLQI = 0/1 and PSSD = 0. Conclusion: Clinical measures alone do not capture the full patient experience. While both QoL and clinical symptoms are responsive to highly effective treatment, a subset of patients with complete clinical response is still impacted by their psoriasis. Further investigation into this population is warranted. Trial registration: ClinicalTrials.gov, NCT02207231. [ABSTRACT FROM AUTHOR]

Introduction: Knowing the remission duration after biologics discontinuation in patients with psoriasis is important, especially when disease relapse is defined as the restart of systemic agents, because it also reflects the real-world clinical practice when topical treatment alone is not adequate for disease control, and a systemic treatment, including biologic, is needed. Biologics are currently indicated for patients with psoriasis who are candidates for systemic treatments. Methods: We included 42 patients who were followed up with regularly after the end of risankizumab, guselkumab and mirikizumab trials and investigated the drug-free remission (DFR). A Kaplan–Meier survival analysis and Cox regression model were employed to identify the possible risk factors for relapse. Results: Overall, 38/42 (90.5%) patients experienced relapses after discontinuing trial biologics during the follow-up period of at least 96 weeks and up to 227 weeks. In all patients with relapse, the median DFR was 104 days. Kaplan–Meier survival analysis revealed a significant 1-year drug-free survival (DFS) difference between risankizumab (Z) and guselkumab (T) + mirikizumab (M) (p = 0.0462). A difference in DFS curves was noted when patients were categorized by disease duration > or ≤ 2 years (p = 0.1577) and maintenance of a psoriasis area and severity index score (PASI) of 90 at the end of trials (p = 0.1177). Univariate Cox regression model identified that age [hazard ratio (HR) = 1.030 (1.000–1.060), p = 0.0467] and disease duration [HR = 1.046(1.009–1.084), p = 0.0134] were significantly associated with relapse risk. A risk model was established on the basis of multivariable Cox regression results. Risk value = 0.021038 * Age + 0.515628 * Biologic_type (Z = 0,T/M = 1) + 0.025048 * Disease_Duration. The validated patients were divided into two groups by median risk value (1.5). The high-risk group (risk value > 1.5) had a non-significant higher relapse risk than the low-risk group (risk value < 1.5), with a hazard ratio of 1.62 [95% confidence interval (CI) = 0.82–3.23, p = 0.1809]. Conclusion: Types of biologics used, disease duration > or ≤ 2 years, and PASI 90 improvement at the end of trial affect the 1-year DFS after biologics discontinuation. Further studies consisting of a larger patient number and longer follow-up period are needed to verify our findings. Trial registration: ClinicalTrials.gov identifiers NCT02694523, NCT03047395, NCT02207224, NCT02576431, NCT03482011, and NCT03556202. [ABSTRACT FROM AUTHOR]

Introduction: Given the chronic nature of psoriasis (PsO), more studies are needed that directly compare the effectiveness of different biologics over long observation periods. This study compares the effectiveness and durability through 12 months of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis in a real-world setting. Methods: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of 1981 adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. The study compares the effectiveness of anti-IL-17A biologics with other approved biologics and provides pairwise comparisons of seven individual biologics versus ixekizumab. The primary outcome was defined as the proportion of patients who had at least a 90% improvement in Psoriasis Area and Severity Index score (PASI90) and/or a score of 0 or 1 in static Physician Global Assessment (sPGA). Secondary objective comparisons included the proportion of patients who achieved PASI90, PASI100, a Dermatology Life Quality Index (DLQI) score of 0 or 1, and three different measures of durability of treatment response. Unadjusted response rates are presented alongside the primary analysis, which uses frequentist model averaging (FMA) to evaluate the adjusted comparative effectiveness. Results: Compared to the other biologics cohort, the anti-IL-17A cohort had a higher response rate (68.0% vs. 65.1%) and significantly higher odds of achieving the primary outcome at month 12. The two cohorts had similar response rates for PASI100 (40.5% and 37.1%) and PASI90 (53.9% and 51.7%) at month 12, with no significant differences between the cohorts in the adjusted analyses. At month 12, the response rates across the individual biologics were 53.5–72.6% for the primary outcome, 27.6–48.3% for PASI100, and 41.7–61.4% for PASI90. Conclusions: These results show the comparative effectiveness of biologics at 6 and 12 months in the real-world setting. [ABSTRACT FROM AUTHOR]

Introduction: The National Psoriasis Foundation (NPF) recommends evaluating patient response to treatment at week 12, with a target response of ≤ 1% body surface area (BSA) affected by plaque psoriasis and an acceptable response of BSA ≤ 3% or ≥ 75% improvement. This post hoc analysis compared the achievement of NPF target and acceptable responses for ixekizumab (IXE) versus other biologics. Methods: Outcomes were evaluated at week 12 for patients with moderate-to-severe plaque psoriasis from four head-to-head randomized clinical trials (RCTs; UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) and one real-world prospective observational study (Psoriasis Study of Health Outcomes; PSoHO). RCT patients were treated with IXE or etanercept (ETN; UNCOVER-2/3), guselkumab (GUS; IXORA-R), or ustekinumab (UST; IXORA-S). PSoHO patients were treated with anti-interleukin (IL)-17A biologics (IXE, secukinumab, SEC) and other approved biologics for the treatment of plaque psoriasis. Patients with missing outcomes were imputed as non-responder imputation. For RCT data, statistical comparisons between treatment groups were performed using Fisher's exact test with no multiplicity adjustments. For real-world data, adjusted comparative analyses were performed using frequentist model averaging (FMA) and reported as odds ratio (OR). Results: Across the four head-to-head clinical trials analyzed, significantly higher proportions of patients achieved target and acceptable responses at week 12 with IXE versus ETN, GUS, or UST. Likewise, the proportion of PSoHO patients achieving target and acceptable response at week 12 was higher with IXE compared with other individual biologics. Adjusted comparative analyses showed that IXE had significantly greater odds of target and acceptable response at week 12 versus SEC, GUS, risankizumab (RIS), adalimumab (ADA), UST, and tildrakizumab (TILD) and numerically greater odds of target and acceptable response at week 12 versus brodalumab (BROD). Conclusion: Across both clinical studies and real-world settings, more patients treated with IXE achieved NPF target and acceptable responses at week 12 compared with those treated with other biologics. Trial Registration: UNCOVER-2 (NCT01597245); UNCOVER-3 (NCT01646177); IXORA-R (NCT03573323); IXORA-S (NCT02561806); PSoHO (EUPAS24207). [ABSTRACT FROM AUTHOR]

Introduction: Deucravacitinib, a newly approved oral medication for the treatment of patients with moderate to severe plaque psoriasis, demonstrated efficacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs). A systematic review and network meta-analysis (NMA) indirectly compared deucravacitinib with other relevant systemic biologic/nonbiologic treatments. Methods: Online databases were searched for RCTs published through October 2021. Eligible studies were head-to-head comparisons between systemic therapies and/or placebo reporting 50%, 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index (PASI) from baseline in adults with moderate to severe plaque psoriasis. Comparisons included tumor necrosis factor inhibitors, interleukin (IL)-17, IL-23, and IL 12/23 inhibitors, and systemic nonbiologics. A multinomial Bayesian NMA was used to derive estimates of the relative efficacy of deucravacitinib and other systemic therapies. Response probabilities for each treatment and corresponding 95% credible intervals (CrIs) for achieving a PASI response were calculated over short-, mid-, and long-term follow-up (weeks 10–16, 24–28, and 44–60). Results: The NMA included 47 RCTs. Deucravacitinib showed the highest PASI 75 response rates among nonbiologic systemic therapies across time points. Deucravacitinib PASI 75 response rate (95% CrI) over short-term follow-up was 54.1% (46.5–61.6), within the range of first-generation biologics (etanercept, 39.7% [31.6–48.3]; infliximab, 79.0% [74.0–83.5]). At mid-term follow-up, deucravacitinib PASI 75 increased to 63.3% (58.0–68.4). At long-term follow-up, deucravacitinib PASI 75 was 65.9% (58.0–73.4), comparable to first-generation biologics adalimumab (62.8%; 55.3–69.6) and ustekinumab (68.0%; 64.6–71.5). Conclusions: Patients receiving deucravacitinib were more likely to achieve PASI 75 response versus apremilast and methotrexate across all time points. The long-term PASI 75 response rate for deucravacitinib was similar to those of adalimumab and ustekinumab. The approval of deucravacitinib offers patients the choice of an oral therapy with long-term efficacy similar to that of some biologics. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to retrospectively examine the drug survival of tumor necrosis factor (TNF)-alpha inhibitors and switched subsequent biologic agents after discontinuation of TNF inhibitors. Methods: This real-world setting study was conducted at a single academic center. We included patients who were treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021. Results: No significant differences were noted in drug survival between the three TNF inhibitors. The 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. Of the patients who discontinued TNF inhibitors for any reason (n = 137), 105 chose biologics as their subsequent treatment. The subsequent biologics included 31 cases of TNF inhibitors (adalimumab in 20, certolizumab pegol in 1, and infliximab in 10), 19 of interleukin-12/23 inhibitor (ustekinumab), 42 of interleukin-17 inhibitors (secukinumab in 19, brodalumab in 9, and ixekizumab in 14) and 13 of interleukin-23 inhibitors (guselkumab in 11, risankizumab in 1, and tildrakizumab in 1). Cox proportional hazards analysis for the subsequent drugs in cases of discontinuation due to inadequate efficacy revealed that female sex was a predictor of drug discontinuation (hazard ratio 2.58, 95% confidence interval 1.17–5.70) and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug persistence (hazard ratio 0.37, 95% confidence interval 0.15–0.93). Conclusions: Interleukin-17 inhibitors may be a favorable option for patients who need to switch from TNF inhibitors due to inadequate efficacy. However, this study is limited by the small number of cases and its retrospective design. Plain Language Summary: With many biologic options available for the treatment of psoriasis, choosing the optimal drug can be challenging, especially when switching drugs. Tumor necrosis factor (TNF) inhibitors are the oldest category of biologics used for psoriasis, with adalimumab and infliximab being available since 2010 and certolizumab pegol since 2019 in Japan. In this study, we examined the drug survival of TNF inhibitors in patients treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021. No significant differences were noted in drug survival between the three TNF inhibitors, and the 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. We examined the drug survival of subsequent biologics used by patients who discontinued TNF inhibitors for any reason (n = 137) and found that among patients who discontinued TNF inhibitors due to inadequate efficacy, female sex was a predictor of drug discontinuation and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug continuation. The study results suggest that interleukin-17 inhibitors is a favorable option for patients who discontinue TNF inhibitors due to inadequate efficacy and need to switch to other agents. However, this study has limitations, including the small number of cases and the single-center and retrospective study design. [ABSTRACT FROM AUTHOR]

Psoriasis vulgaris is a systemic, chronic inflammatory disease affecting 2–3% of the population. Recent advances in the understanding of the pathophysiology of psoriatic disease have facilitated the development of novel therapeutic options with improved safety and efficacy. This article is coauthored by a patient with a lifelong history of psoriasis who experienced multiple treatment failures. He details his diagnosis and treatment experiences, as well as the physical, mental, and social ramifications of his skin condition. He then goes on to elaborate how evolutions in the treatment of psoriatic disease have impacted his life. This case is then discussed from the perspective of a dermatologist specializing in inflammatory skin disorders. We highlight the clinical features of psoriasis, its medical and psychosocial comorbidities, and the current landscape of psoriatic disease treatments. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis (PsO), an immune-mediated inflammatory skin disorder, has substantial negative impact on patients' quality of life. Secukinumab, an approved treatment for moderate-to-severe plaque PsO, has an established long-term efficacy and safety profile. This study aims to provide real-world evidence of long-term effectiveness and retention rate of secukinumab in Vietnamese patients with PsO. Methods: This retrospective, observational study collected medical records of adult patients with moderate-to-severe PsO receiving secukinumab treatment from Ho Chi Minh City Hospital of Dermato-Venereology. The primary objective was to evaluate secukinumab effectiveness in PsO as measured by 75% improvement in psoriasis area and severity index (PASI 75) at month 12. Secondary objectives were PASI 90/100, absolute PASI ≤ 3 and ≤ 5, Dermatology Life Quality Index (DLQI), and retention rate over 48 months. Results: In total, 232 patients with moderate-to-severe PsO met inclusion criteria; 68.1% were male, with median age and age of onset of 39 and 27.5 years, respectively. Median time from onset of PsO to secukinumab treatment was 120 months, 95.3% were prior biologics/disease-modifying antirheumatic drugs naive and 41.4% received concomitant therapies for PsO; 82.3% had national insurance coverage. At month 12, 93.9% of patients achieved PASI 75 (primary endpoint); 80.2/56.9% achieved PASI 90/100; 91.4 and 84.8% patients achieved absolute PASI ≤ 5 and ≤ 3, respectively. The response was sustained over 48 months, with 91.9%/78.0%/52.0% of patients achieving PASI 75/90/100, 89.5% and 82.1% patients achieving absolute PASI ≤ 5 and ≤ 3, respectively. At month 12, 61.4% of patients achieved DLQI 0/1 which was sustained up to month 48 (69.2%). Secukinumab adherence rate of 84.9% at month 12 dropped to 34.2% at month 48. Patients receiving concomitant therapy and national insurance showed higher adherence rate. Conclusion: Secukinumab demonstrated long-term effectiveness in real-world Vietnamese patients with moderate-to-severe PsO, with treatment adherence being higher in patients having concomitant therapies and national insurance. [ABSTRACT FROM AUTHOR]

Introduction: Risankizumab is a humanized monoclonal antibody that selectively targets interleukin-23. It is approved for treatment of moderate-to-severe plaque psoriasis. We conducted a 52-week monocentric retrospective study to evaluate the effectiveness and safety of risankizumab in a real-life setting. Methods: Our study included 131 adults with moderate-to-severe plaque psoriasis all treated with risankizumab for at least 52 weeks. Patient characteristics and PASI (Psoriasis Area and Severity Index) at each visit were recorded. The percentages of patients achieving 75%/90%/100% (PASI 75/90/100) improvement in PASI with respect to baseline were registered. Results: At week 52, 93.9%, 78.6%, and 61.1% of patients achieved PASI 75/90/100, respectively. An absolute PASI ≤ 2 was reached by 90.8% at week 52. The higher body mass index and the presence of cardio-metabolic comorbidities did not interfere with the odds of reaching PASI 75/90/100 at each time-point. At week 52, comparable percentages of patients achieved PASI 100, regardless of the involvement of difficult-to-treat-areas. No significant safety findings were recorded and none of the patients had to interrupt the treatment because of adverse events. Conclusions: Our findings confirmed that risankizumab is a safe and effective therapeutic option for the treatment of a wide "real-life" cohort of patients with psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Tildrakizumab 200 mg/2 mL pre-filled syringe is a new preparation of tildrakizumab that is developed to facilitate patients' compliance. This phase I clinical trial compares the local tolerability, safety, and subjects' preferred method of administration of tildrakizumab when administered as a new single 200 mg/2 mL subcutaneous injection or as two 100 mg/1 mL subcutaneous injections in healthy subjects. Methods: Visual analogue scores were used to self-assess injection site pain immediately (< 1 min) after each administration and at 1 h and 48 h after each administration. Treatment injection site reactions were assessed at 1 h and 48 h after each administration. Treatment safety was monitored throughout the study period. Subjects' preferred method of administration was assessed 4 weeks after the last administration (day 56). Results: No statistically significant difference in visual analogue scores and injection site reactions was detected between the two treatments. Treatment-emergent adverse events were mild, and there were no deaths or serious adverse events. Most subjects (61.5%) preferred the treatment when administered as a single 200 mg/2 mL subcutaneous injection rather than as two 100 mg/mL subcutaneous injections. Conclusions: Administration of 200 mg tildrakizumab as a single 2 mL subcutaneous injection was safe, well tolerated, and preferred over two separate 100 mg/1 mL subcutaneous injections by healthy subjects. Eudract No. 2020-000183-37. [ABSTRACT FROM AUTHOR]

Introduction: It can be challenging for dermatologists to keep abreast of the growing evidence from published indirect comparisons (ICs) of treatments for psoriasis. The objective of this analysis was to summarise comparative clinical efficacy and safety findings from ICs of systemic biologics for the treatment of moderate-to-severe psoriasis and to identify factors potentially affecting efficacy outcomes and their possible implications for clinical decision making. Methods: An umbrella review of short- and long-term efficacy and safety findings from 26 ICs visually compared 90% improvement in Psoriasis Area Severity Index (PASI90) treatment rankings and three safety outcome rankings side by side. Pearson's correlation coefficients measured the strength of the association between each pair of ICs on the basis of identified factors that could potentially affect efficacy findings. Results: Some consistency in short-term PASI90 efficacy rankings was observed for certain drugs, although rankings for most drugs varied by IC. Factors potentially affecting efficacy outcomes included the use of different methodologies for head-to-head comparison and statistical analyses, and variation in drugs and classes included treatment dosing and duration, outcome definitions and effect measures reported between ICs. Considerable variation in these factors was found across all 26 ICs. Comparative safety information of value to physicians was limited. Conclusions: Substantial differences were identified between ICs in factors that could potentially affect efficacy outcomes. Treatment rankings must be interpreted alongside actual differences in IC outcomes to allow conclusions on clinical relevance. Drugs within a class cannot be considered of equal efficacy: therapies should be considered individually rather than by class. Plain Language Summary: Plain language title: Interpreting indirect comparison efficacy findings in psoriasis Psoriasis is a chronic, often life-long, inflammatory skin disease with a high disease burden and considerable quality of life impairment, particularly in moderate-to-severe psoriasis. We, an international group of researchers, aimed to highlight the importance of fully understanding indirect comparisons (ICs) used to compare the efficacy and safety of multiple treatments for moderate-to-severe plaque psoriasis outside of head-to-head clinical trials, to effectively use their findings in clinical practice. We visually compared side-by-side efficacy and safety results and rankings from 26 ICs of systemic biologics for psoriasis and described our findings. We also identified factors with the potential to affect the efficacy outcomes of these ICs (Fig. 2) and looked for similarities and differences between the 26 ICs in terms of these factors. Finally, given what we found, we considered how the results of these ICs should be interpreted to support physicians in choosing the treatments best suited to the needs of their patients with psoriasis. Treatment ranking results from ICs (based on, for example, efficacy or safety outcomes) need to be interpreted together with information on actual numerical differences between treatment effects to inform the physician's decisions. When selecting the most efficacious treatment, drugs within a class cannot be considered equal, and therapies should be considered individually rather than by class. Substantial differences were identified between ICs with respect to factors that could potentially affect efficacy outcomes, highlighting the need to fully understand each individual analysis before making decisions based on its findings. Comparative safety information was limited. [ABSTRACT FROM AUTHOR]

Introduction: Biologics have expanded the treatment options in the management of patients with moderate-to-severe psoriasis. The objective of this study was to describe patient characteristics and previous treatments in psoriasis patients newly treated with guselkumab, secukinumab, or ixekizumab. Methods: This retrospective study included patients ≥ 18 years old with psoriasis in the USA who were newly treated with guselkumab, secukinumab, or ixekizumab between 1 July 2017 and 31 March 2019 in the Modernizing Medicine Data Services database (MMDS). Patients were indexed on their first prescription or injection record of guselkumab, secukinumab, or ixekizumab, and three mutually exclusive cohorts were created. Patients were required to have evidence of moderate-to-severe psoriasis, defined as Physician Global Assessment (PGA) score of 3 or 4, or body surface area (BSA) ≥ 10% on index date or within 12 months before index. Baseline characteristics, including treatment history, were reported for each cohort. Results: The study population included 461 guselkumab, 619 secukinumab, and 375 ixekizumab patients. The median age across cohorts was 51–52 years. Median baseline BSA ranged from 15% to 20%; 16.1–29.3% of patients had a PGA of 4 and over half of patients were obese prior to index. Approximately 40% of patients had comorbid cardiovascular disease and 20.8–24.2% of patients had a psychiatric disorder. About half of patients in each cohort had prior biologic use, of which adalimumab was most common (28.2–34.9%) across the cohorts. Conclusion: This real-world study describes the characteristics of patients with moderate-to-severe psoriasis receiving biologic treatments. [ABSTRACT FROM AUTHOR]

Introduction: Both early clinical improvement and long-term maintenance of clinical efficacy of treatments matter to patients with psoriasis. We compared cumulative clinical benefits of treatment with biologics over 1 year based on the area under the curve (AUC) for Psoriasis Area and Severity Index (PASI) 100 and PASI 90 responses in patients with moderate-to-severe psoriasis using a network meta-analysis (NMA). Methods: Published phase 3 randomized, placebo- or active-controlled clinical trial data for biologics approved for the treatment of moderate-to-severe psoriasis were obtained from a systematic literature review up to 30 September 2020. Eighteen clinical trials that included data from baseline to 48 or 52 weeks where AUC could be calculated were included. Data were compared using a fixed-effect model with a separate random-effect baseline model to account for effects of the placebo arm. Cumulative clinical benefit was estimated using the AUC for PASI 100 and PASI 90 responses (complete and almost-complete skin clearance, respectively). Normalized AUC was compared using Bayesian NMA. Cumulative days of response were calculated using normalized AUC and study duration. Results: Interleukin (IL)-17 and IL-23 inhibitors demonstrated greater cumulative clinical benefits for both PASI 100 and PASI 90 versus IL-12/23 and tumor necrosis factor inhibitors. Over 52 weeks, cumulative days with PASI 100 were greatest with ixekizumab [158.7 (95% credible interval, 147.4, 170.0) days] followed by risankizumab [154.0 (144.9, 163.4) days]; PASI 90 days were greatest with risankizumab [249.3 (239.5, 259.2) days] followed by ixekizumab [238.8 (227.1, 250.8) days]. Both ixekizumab and risankizumab showed greater cumulative days with PASI 100 or PASI 90 responses versus secukinumab [117.9 (110.7, 125.2) and 215.5 (208.2, 223.1) days, respectively] and greater cumulative days with PASI 100 versus guselkumab [130.7 (120.5, 140.9) days]. Conclusion: For complete and almost-complete skin clearance, ixekizumab and risankizumab provided the greatest cumulative clinical benefits over 1 year. [ABSTRACT FROM AUTHOR]

Introduction: Patients with moderate-to-severe plaque psoriasis who experience poor clinical outcomes, including patients with obesity or prior treatment, need improved treatment options. Risankizumab specifically inhibits interleukin 23 and has demonstrated superior efficacy in active-comparator studies in patients with moderate-to-severe plaque psoriasis. We compared the efficacy of risankizumab with that of secukinumab across patient subgroups. Methods: Subgroup analyses using data from the phase 3 IMMerge study (NCT03478787) were performed. Efficacy in adults with moderate-to-severe psoriasis treated with risankizumab 150 mg and secukinumab 300 mg was assessed as the proportion of patients who achieved ≥ 90% improvement in Psoriasis Area Severity Index (PASI 90) at week 52 across demographics and disease characteristics. Post hoc analyses evaluated the proportion of patients who achieved PASI 90 and the least-squares mean percent PASI improvement from baseline at week 52 by body weight and body mass index (BMI), PASI 90 by prior treatment, and clinical response [PASI 90, PASI 100, and/or static Physician's Global Assessment (sPGA) score of clear (0) or almost clear (1)] at week 16 and maintained particular response at week 52. Logistic regression analyses examined the effect of covariates (age, sex, BMI, baseline PASI, treatment) and potential interactions on PASI 90 at week 52. Results: More patients who received risankizumab (n = 164) compared with secukinumab (n = 163) achieved PASI 90 at week 52, regardless of demographics and disease characteristics (BMI, prior treatment, disease duration, and maintenance of clinical response at week 52). Improvements in PASI were greater in patients taking risankizumab than those taking secukinumab, regardless of weight or BMI. Results from logistic regression analysis showed treatment type had a significant impact on PASI 90 (risankizumab versus secukinumab, p < 0.0001). Conclusion: Risankizumab showed consistently greater efficacy compared with secukinumab across different patient subgroups, and this was maintained through 52 weeks. Trial Registration: ClinicalTrials.gov identifier; NCT03478787. Plain Language Summary: Patients with moderate-to-severe plaque psoriasis are often unable to achieve treatment success with currently available biologic therapies when they have other conditions, such as obesity, or have previous biologic therapy exposure and/or failure. We studied patients in the IMMerge phase 3 clinical trial (NCT03478787) to assess the efficacy of risankizumab compared with secukinumab for the treatment of plaque psoriasis and to determine risankizumab's ability to remain effective after 52 weeks of administration. In our analysis, we looked across patient subgroups including patient body weight, body mass index, previous use of biologic therapies, length of time patients had been living with their disease, and the durability of risankizumab efficacy at 52 weeks. Results from our analysis showed that patients had greater success with risankizumab compared with secukinumab in treating their plaque psoriasis, despite their age, sex, race, and disease characteristics, and that risankizumab remained effective in treating plaque psoriasis at week 52. Previously reported safety results from the IMMerge clinical trial showed that there were no new concerns regarding side effects for either risankizumab or secukinumab. Overall, these results support the use of risankizumab to treat patients, including those who have other conditions or may not have had success with other therapies in treating their plaque psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Biologic treatments for psoriasis are commonly switched. Treatment persistence represents an important parameter related to long-term therapeutic performance. The objective of the study was to analyse the real-world persistence with biologics over time in the treatment of psoriasis. Methods: A retrospective observational study of adults with psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Patients included were treated with a biologic between 2010 and 2018. Treatment episodes were identified from the drug's date of dispensation recorded in the Prescribed Drug Register to the end of supply of the drug. Median persistence was estimated by Kaplan–Meier survival curves for patients who received adalimumab, etanercept, secukinumab, ustekinumab and ixekizumab. Descriptive analysis of change in persistence over time for 3-year running cohorts was also carried out. Results: A total of 2292 patients were analysed. Patients who received ustekinumab had the longest median persistence [49.3 months, 95% confidence interval (CI) 38.0–59.1] and etanercept the shortest (16.3 months, 95% CI 14.5–19.0). Median persistence was longer in biologic-naive than biologic-exposed patients. Persistence for ustekinumab decreased by almost 50% over the study period, from a median of 62.3 (95% CI 45.6–∞) months in 2010–2011 to 32.7 (21.2–49.3) months in 2014–2016. Conclusions: Persistence with biologics was, on average, relatively low, given the chronic nature of psoriasis. Changes in persistence over time seemed to be attributable to changes in the therapeutic landscape, providing patients with more options to switch biologic treatments if their current management was considered suboptimal. [ABSTRACT FROM AUTHOR]

The outbreak of the novel coronavirus known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causing COVID-19 was first reported in late December 2019. Many patients with psoriasis on biologic therapy have asked their medical providers about the effect of biologics on COVID-19. However, it is currently unknown how biologic therapy for psoriasis might impact patients with psoriasis and COVID-19. In this article, we report on the clinical course of two patients on biologic medication for psoriasis who developed COVID-19 and successfully recovered from SARS-CoV-2 infection. Both patients presented with fever and respiratory symptoms, but neither patient required hospitalization. While more research is needed, it is reassuring to know that successful recovery is possible after COVID-19 infection in patients on biologic therapy for psoriasis. [ABSTRACT FROM AUTHOR]

With the emergence of the novel coronavirus disease (COVID-19) viral pandemic, there is uncertainty whether biologic agents for psoriasis may place patients at a higher risk for infection or more severe disease course. This commentary offers patient counseling recommendations based on the current available evidence. While there are currently no specific data for psoriasis biologics and COVID-19, data are presented here from phase III clinical trials of psoriasis biologics on rates of upper respiratory infection, influenza, and serious infection. Overall these data reveal that on the whole, psoriasis biologics do not show major increases in infection risk compared to placebo during the course of these trials. However, as the COVID-19 virus is a novel pathogen that is associated with mortality in a subset of patients, a cautious approach is warranted. We discuss factors that may alter the benefit–risk ratio of biologic use during this time of COVID-19 outbreak. Ultimately, treatment decisions should be made on the basis of dialogue between patient and provider, considering each patient's individualized situation. Once this pandemic has passed, it is only a matter of time before a new viral disease reignites the same issues discussed here. [ABSTRACT FROM AUTHOR]

Introduction: Rapid improvement of psoriasis is valued by patients and should be considered to be an important factor in treatment selection. We investigated Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) response rates within the first 12 weeks of treatment to compare the rapid response of 11 biologic therapies for moderate-to-severe psoriasis using Bayesian and Frequentist network meta-analyses (NMA). Methods: A systematic literature review was conducted to identify phase 3, double-blind, randomized, controlled trials for adult patients with moderate-to-severe psoriasis treated with interleukin (IL)-17 (brodalumab, ixekizumab, secukinumab), IL-12/-23 (ustekinumab), IL-23 (guselkumab, risankizumab, tildrakizumab), or tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab). Outcome measures extracted from 32 publications were ≥ 75, ≥ 90, or 100% improvement in PASI score (PASI 75, PASI 90, or PASI 100, respectively) at weeks 2, 4, 8, and 12 and DLQI (0,1), where score (0,1) indicates no effect on patient's life, at week 12. Bayesian NMA (BNMA) used fixed-treatment effect and random-baseline effect, normal independent models. Frequentist NMA (fNMA) was conducted as sensitivity analyses to test the robustness of the findings. Results: Based on BNMA and fNMA, brodalumab and ixekizumab showed the most rapid treatment effects on PASI 75 at weeks 2, 4, and 8 and on PASI 90 and PASI 100 at weeks 2, 4, 8, and 12; ixekizumab overlapped with risankizumab on PASI 75 at week 12. Brodalumab, ixekizumab, and secukinumab yielded higher DLQI (0,1) gains at week 12 compared to all of the other biologics studied. Additional measures of quality of life were not assessed in this report. Conclusions: Ixekizumab and brodalumab provide the most rapid response and earliest clinical benefit at week 2 among all of the biologics studied, including other biologic treatments such as secukinumab, ustekinumab, guselkumab, adalimumab, and etanercept. BNMA and fNMA results showed similar relative effect estimates and treatment rankings. Funding: Eli Lilly and Company. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease which predominately affects children and usually clears up during infancy or childhood. However, AD may persist with a chronic relapsing course until adulthood or develop at a later age. AD treatment can often be complicated. Treating moderate-to-severe AD can be challenging: only a few therapeutic options are available, with cyclosporine being the only approved and labeled systemic drug. In the last few years, advances in the knowledge of AD pathogenesis have been made that can provide the basis for developing new topical and systemic drugs. Among them, biologic drugs targeting specific cytokines involved in the development of the disease will probably revolutionize AD therapy. Currently, dupilumab, a monoclonal antibody that binds to the shared alpha chain subunit of the receptors for IL-4 and IL-13, is the only biologic drug licensed for the treatment of AD in adults. However, other biologic drugs that selectively target some key cytokines in AD pathogenesis (IL-13, IL-31, and IL-22) are also being studied. In this review, we discuss all of the biologic drugs that have been studied for AD treatment. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials have shown brodalumab to have better efficacy than ustekinumab for the treatment of moderate-to-severe psoriasis. An estimation of the cost-effectiveness of brodalumab vs. ustekinumab is warranted and may be useful for treatment decision-making processes, especially in the context of the cost considerations of the current US healthcare system. Therefore, we compared the cost-effectiveness of brodalumab with ustekinumab for treatment of moderate-to-severe psoriasis in biologic-naïve and biologic-experienced patients in the USA.Methods: An Excel-based economic model was developed to estimate and compare total annual costs to health plans associated with treatment with brodalumab vs. ustekinumab per achievement of Psorasis Area and Severity Index (PASI) 75, 90, and 100 for patients with moderate-to-severe psoriasis.Results: For treatment with brodalumab vs. ustekinumab, total annual treatment costs per PASI 75, 90, and 100 were $31,106, $57,776, and $163,069, respectively, lower for a patient naïve to prior biologic treatment; they were $40,535, $65,472, and $223,610, respectively, lower for a patient experienced with prior biologic treatment. In an additional analysis among patients with and without prior biologic failure, they were $52,822, $93,309, and $365,606, respectively, lower for a patient with failure and they were $31,660, $57,128, and $164,996, respectively, lower for a patient without failure.Conclusion: Compared to ustekinumab, treatment with brodalumab was associated with better cost-effectiveness ratios for biologic-naïve and experienced-patients and also patients with and without prior biologic treatment failure. The greater cost-effectiveness of brodalumab was most prominent for biologic-experienced and prior biologic treatment failure patients.Funding: Ortho Dermatologics. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that predominantly affects children. However, it can persist in adulthood and/or start at older ages. Due to its chronic nature and frequently occurring relapses, AD has a substantial effect on patients' quality of life, often requiring long-term systemic treatment, especially in adult patients, who are more frequently refractory to adequate topical treatment with mid- to high-potent corticosteroids and/or calcineurin inhibitors. Therefore, treatment with systemic therapies is often needed to take control of the disease, prevent exacerbations and improve quality of life. However, data regarding systemic treatment effectiveness and long-term safety in adult patients with AD are insufficient. Indeed, standardized international guidelines are lacking, and the treatment approach widely differs among diverse countries. This review focuses on the use of systemic treatments in adult AD patients analyzing published literature. [ABSTRACT FROM AUTHOR]