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Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.
Generalized pustular psoriasis (GPP) is a rare, chronic skin condition characterized by painful, sterile pustules that can occur all over the body. These pustules may also be accompanied by systemic inflammation, which can lead to serious health complications. GPP significantly impacts patients' quality of life and can even be life-threatening. Because the disease is so rare, treatment guidelines have typically been based on those for plaque psoriasis. However, these guidelines do not specifically address the unique needs of GPP. In this review, we analysed the published literature on GPP management, focussing on treatment efficacy, safety and quality of life outcomes. We searched the literature databases Embase and MEDLINE for articles published between 1980 and September 2023. In total, we identified 118 publications on this topic, covering a wide range of therapies; only one of these therapies, spesolimab, reported results from placebo-controlled randomized trials. Based on these trials, spesolimab is now approved for GPP treatment in the USA, Japan, China, the EU and several other countries. Some other therapies are approved exclusively in Japan and Taiwan based on small, open-label studies in the absence of higher-quality data. To date, comparing treatments has been challenging because of different clinical outcomes used to measure effectiveness. However, well-defined endpoints specific to GPP have recently been developed and used in trials. In conclusion, our review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the best treatment strategy.
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Brodalumab is an interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis in adults without response or with loss of response to other systemic therapies. Brodalumab carries a boxed warning in the United States regarding suicidal ideation and behavior, though no causal relationship has been established. Here, we summarize 4 years of pharmacovigilance data, from August 15, 2017, through August 14, 2021, reported to Ortho Dermatologics by US patients and healthcare providers. The most common AEs listed in the brodalumab package insert (incidence ≥1%) and AEs of special interest are described. Brodalumab exposure estimates were calculated using the time between the first prescription-dispensing authorization date and last prescription-dispensing authorization date. Data were collected from 4019 patients with an estimated brodalumab exposure of 4563 patient-years. The most common AE was arthralgia (115 events; 2.52 events per 100 patient-years). No completed suicides and no new suicidal attempts were reported. There were 102 cases with serious infections; however, no serious fungal infections (including no new cases of oral candidiasis) were reported. There were 26 COVID-19 cases, and 3 of the cases with comorbid conditions were fatal. There were no new cases of Crohn’s disease. Of 37 reported malignancies among 32 cases, none were deemed related to brodalumab. Four-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and 3-year pharmacovigilance data. J Drugs Dermatol. 2023;22(4) doi:10.36849/JDD.7344 Citation: Lebwohl M, Koo J, Leonardi C, et al. Brodalumab: 4-Year US pharmacovigilance report. J Drugs Dermatol. 2023;22(4):419-422. doi:10.36849/JDD.7344.
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COVID-19 , Psoriasis , Suicidio , Adulto , Humanos , Anticuerpos Monoclonales/uso terapéutico , Farmacovigilancia , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
INTRODUCTION: Biologic treatments are increasingly being used in the management of moderate to severe plaque psoriasis (PSO). Bimekizumab is a selective inhibitor of both interleukin (IL)-17A and IL-17F approved for the treatment of moderate to severe PSO. Although bimekizumab trials provide comparisons to secukinumab, adalimumab and ustekinumab, there are no further head-to-head comparisons of bimekizumab to other biologics. This network meta-analysis (NMA) aimed to compare the short-term efficacy of bimekizumab versus other biologic systemic therapies for moderate to severe PSO. METHODS: A systematic literature review was conducted to identify randomised controlled trials (RCTs) in patients with moderate to severe PSO. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews and PsycINFO were searched on July 1, 2020. An enhanced multinomial Bayesian NMA model was used to evaluate the comparative efficacy in 50%, 75%, 90% and 100% improvement from baseline Psoriasis Area and Severity Index (PASI 50/75/90/100) at 10-16 weeks. The model was also adjusted for baseline risk, given the variable placebo responses across the trials. RESULTS: Eighty-six RCTs (including 34,476 patients) were included in the NMA. IL-17 and IL-23 inhibitors were the most effective treatments across all PASI levels. At 10-16 weeks, bimekizumab had the highest probability of achieving PASI 75 (92.3%), PASI 90 (84.0%) and PASI 100 (57.8%). Bimekizumab demonstrated statistical superiority over all biologics in achieving PASI 90 and PASI 100 thresholds. For PASI 75, the benefit of bimekizumab was statistically significant compared to all other treatments except risankizumab and ixekizumab. CONCLUSION: This analysis demonstrated that IL-17 and IL-23 inhibitors were highly effective in achieving short-term improvement among patients with moderate to severe PSO. Patients receiving bimekizumab were significantly more likely to achieve PASI 90 or PASI 100 within 10-16 weeks of the first injection than all other biologics.
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INTRODUCTION: Limited real-world data are available comparing multiple biologics on their adherence, persistence, and the use of concomitant biologics in the treatment of moderate-to-severe psoriasis in clinical practice. The objective was to compare persistence of and adherence to ixekizumab (IXE) treatment, as monotherapy or with concomitant medication, versus patients receiving other commonly prescribed biologics. METHODS: Patients who newly initiated IXE, adalimumab (ADA), etanercept (ETN), secukinumab (SEC), or ustekinumab (UST) in IBM MarketScan® databases with diagnosis of psoriasis were identified. Treatment comparisons on medication persistence, adherence, and monotherapy were based on balanced samples after inverse probability of treatment weighting (IPTW). RESULTS: A higher proportion of patients receiving IXE had had previous biologic therapies (50.3%) versus other biologics (ADA: 9.1%, ETN: 10.9%, SEC: 33.9%, UST: 19.7%). Patients treated with IXE showed statistically (p < 0.001) greater persistence than patients treated with SEC, ADA, UST, or ETN at both 1-year follow-up and up to 3 years of follow-up. Adherence for patients treated with IXE was significantly (p < 0.001) higher compared to ADA, ETN, and UST at both 1-year follow-up and up to 3 years of follow-up. There was no significantly higher adherence in patients treated with IXE compared to those treated with SEC at 1-year follow-up, but IXE had higher adherence than SEC (p < 0.05) at 1-3 year follow-up. IXE showed longer time on monotherapy than ADA (p < 0.001), ETN (p < 0.001), SEC (p < 0.05), and UST (p < 0.001) for both 1-year and 1-3 year follow-up. Sensitivity analyses on persistence, adherence, and monotherapy with further model adjustments after IPTW confirmed the findings. CONCLUSIONS: Patients treated with IXE were more persistent on and adherent to treatment and remained on monotherapy longer compared to those on all other commonly prescribed biologics combined or with individual biologics.
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Productos Biológicos , Psoriasis , Adalimumab/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Productos Biológicos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Etanercept/uso terapéutico , Humanos , Cumplimiento de la Medicación , Psoriasis/tratamiento farmacológico , Estudios Retrospectivos , Estados Unidos , Ustekinumab/uso terapéuticoRESUMEN
INTRODUCTION: Number needed to treat (NNT) estimates are a practical metric to help identify the most effective therapies. Our objective is to compare 11 biologic drugs for moderate-to-severe psoriasis in terms of NNT. METHODS: The NNT data were obtained from a Bayesian network meta-analysis of 42 double-blind, randomized, phase 3 clinical trials for 11 biologics (adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab). We determined NNT to achieve Psoriasis Area and Severity Index (PASI) 75/90/100 responses at weeks 4, 8, 12, 16, and 48/52 and Dermatology Life Quality Index (DLQI) response 0, 1 at week 12. RESULTS: Highest efficacy (lowest NNT) was with brodalumab and ixekizumab for PASI 90 at weeks 4, 8, and 12; ixekizumab for PASI 90/100 at week 16; and brodalumab for PASI 100 at week 12. After 48/52 weeks, risankizumab had the highest efficacy for PASI 90/100 overlapping with guselkumab, brodalumab, and ixekizumab for PASI 90 and with brodalumab and ixekizumab for PASI 100. Ixekizumab had the highest efficacy for DLQI (0,1) at week 12. CONCLUSIONS: Brodalumab and ixekizumab had the lowest NNTs for achieving PASI responses at early time points and were not significantly different than risankizumab and guselkumab after 48/52 weeks.
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Productos Biológicos , Psoriasis , Teorema de Bayes , Productos Biológicos/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Humanos , Metaanálisis en Red , Psoriasis/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To assess treatment patterns of Ixekizumab (IXE) and evaluate the speed of onset and long-term clinical and quality-of-life outcomes among a subset of patients who switched from adalimumab (ADA) and secukinumab (SEC) to IXE in a real-world setting. METHOD: A retrospective chart review study was conducted at a single US dermatology referral center. RESULT: 153 patients were included in the study, 69.3% of patients were biologic-experienced. ADA was the most commonly used biologic prior to IXE initiation. 66.7% of patients remained on IXE at the study end. 47.7% of patients received concomitant methotrexate, and usage decreased consistently after 1 month. IXE treatment duration was longer among patients who were early responders (achieved sPGA (0,1) at 1 month) vs. non-early responders. 69.4% and 43.3% of patients who switched from ADA and SEC to IXE achieved sPGA (0,1) by week 4, respectively. CONCLUSION: Patients who switched to IXE, specifically from ADA or SEC, had rapid treatment response as well as desirable long-term outcomes. IXE persistence was longer among early responders than non-early responders. Concomitant usage of methotrexate prior to switching to IXE and as a concomitant bridging treatment was reduced after IXE initiation while the proportion of patients achieving treatment targets remained high.
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Productos Biológicos , Dermatología , Psoriasis , Adalimumab/uso terapéutico , Anticuerpos Monoclonales Humanizados , Productos Biológicos/uso terapéutico , Humanos , Metotrexato/uso terapéutico , Psoriasis/tratamiento farmacológico , Derivación y Consulta , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Brodalumab, an interleukin-17 receptor A antagonist, is approved for treatment of moderate-to-severe plaque psoriasis in adults without response or with loss of response to other systemic therapies. In the United States, there is a boxed warning for brodalumab regarding suicidal ideation and behavior; however, no causal relationship between brodalumab and suicidality was established during pivotal trials. In the 2-year pharmacovigilance data, no completed suicides or suicide attempts were reported. The most frequent adverse event (AE) was arthralgia. The safety profile of brodalumab is now being updated after 3 years of pharmacovigilance data. Here, we outline pharmacovigilance data reported to Ortho Dermatologics by patients and healthcare professionals in the United States from August 15, 2017, to August 14, 2020. Brodalumab exposure estimates were obtained by calculating the time between first and last prescription-dispensing authorization dates. Data from 1854 patients were collected, and brodalumab exposure was estimated to be 2736 patient-years. The most frequent AE was arthralgia (111 events; 0.04 events per patient-year). One episode of suicide attempt was reported in a patient with a history of depression. No completed suicides were reported. There were 81 serious infections reported, none of which were fungal. Over the 3-year period, 30 malignancies occurred in 25 patients, none of which were determined to be related to brodalumab. Three-year pharmacovigilance data are consistent with the safety profile of brodalumab previously reported in long-term analyses of clinical trials and the 2-year pharmacovigilance data.
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Farmacovigilancia , Psoriasis , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Humanos , Psoriasis/tratamiento farmacológico , Receptores de Interleucina-17/antagonistas & inhibidores , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Long-term efficacy, safety, and quality of life with ixekizumab (IXE) through 5 years in UNCOVER-1 and UNCOVER-2 patients with baseline scalp, nail, or palmoplantar psoriasis were assessed. METHODS: Patients included in this intent-to-treat subanalysis had baseline involvement in at least one of the three anatomic areas (scalp, fingernail, or palmoplantar locations) and 1) received IXE through week 60, with a 160-mg starting dose 80 mg Q2W through week 12 and Q4W thereafter, 2) achieved a static Physician’s Global Assessment score of 0 or 1 at week 12, and 3) completed week 60 and continued treatment with IXE Q4W or were escalated to Q2W during the long-term extension. Efficacy outcomes (e.g., percent improvement in Psoriasis Scalp Severity Index [PSSI], Nail Psoriasis Severity Index [NAPSI], Palmoplantar Psoriasis Area and Severity [PPASI], and Dermatology Life Quality Index [DLQI]) were summarized by descriptive statistics through week 264. RESULTS: Patients rapidly achieved and sustained improvements in scalp, nail, and palmoplantar psoriasis for up to 5 years with IXE. Patients achieved complete clearance at year 5: observed (scalp, 82%; nail, 73%; palmoplantar, 96%) and mNRI (scalp, 77%; nail, 67%; palmoplantar, 85%). Up to 80% of patients reported DLQI 0,1 responses at week 12, which were sustained through week 264. No increases in the number of annual treatment-emergent adverse events were observed from years 1–5. CONCLUSION: Patients receiving IXE for 5 years sustained high rates of improvement in scalp, nail, and palmoplantar psoriasis, with a long-term quality of life benefit with no unexpected safety signals. J Drugs Dermatol. 2021;20(8):880-887. doi:10.36849/JDD.6101.
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Psoriasis , Fármacos Dermatológicos/efectos adversos , Método Doble Ciego , Etanercept , Humanos , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
INTRODUCTION: Psoriasis Longitudinal Assessment and Registry (PSOLAR) was designed in 2007 as the first disease-based registry for patients with psoriasis. OBJECTIVE: The aim of this study was to discuss methodological limitations and post hoc analyses in long-term safety registries using learnings from analyses of a potential safety risk for major adverse cardiovascular events (MACE) in PSOLAR. METHODS: PSOLAR is an international observational study of over 12,000 psoriasis patients that was conducted to meet postmarketing safety commitments for infliximab and ustekinumab. A recent annual review of registry data indicated a potential MACE risk for ustekinumab vs. non-biologics based on prespecified COX model regression analyses, which yielded an adjusted hazard ratio (HR) of 1.533 (95% confidence interval [CI] 1.103-2.131). Therefore, we conducted a comprehensive review of key statistical methodology and implemented post hoc analytical methods to address specific limitations. RESULTS: The following limiting factors were identified: (1) inclusion of both prevalent and incident (new) users of biologics; (2) unanticipated imbalances in patient characteristics between treatment cohorts at baseline; (3) limited availability of relevant clinical data after enrollment; and (4) divergence of characteristics associated with outcomes among comparator groups over time. The analysis was modified to include only incident users, propensity scores were used to weight HRs, and adalimumab was deemed a more clinically appropriate comparator. The revised HR was 0.820 (95% CI 0.532-1.265), indicating no meaningful increase in MACE risk for ustekinumab. CONCLUSION: Our results, which do not support a causal association between ustekinumab exposure and MACE risk, underscore the need for ongoing assessment of analytical methods in long-term observational studies.
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Productos Biológicos , Psoriasis , Adalimumab , Productos Biológicos/efectos adversos , Humanos , Infliximab , Estudios Observacionales como Asunto , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Sistema de Registros , Ustekinumab/uso terapéuticoRESUMEN
INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is an approved treatment for plaque psoriasis. This study aimed to use animated visualizations as a tool to simplify complex data from ixekizumab clinical trials. METHODS: Animated visualizations were developed to show outcomes from ixekizumab clinical trials and a Bayesian network meta-analysis of 11 approved biologics. The visualizations simultaneously highlighted both aggregate scores and the individual progression of patients over the course of treatment. RESULTS: The animations provided key messages and information from the complex data in efficient and scientific ways that were also visually pleasing and simple to understand. The animations highlighted (1) rapid reduction in disease severity from baseline; (2) sustained efficacy of ixekizumab in the treatment of skin and nail psoriasis; (3) side-by-side comparisons of treatment efficacy and clinical improvement across trials; (4) simultaneous visual presentation of individual results with summary response over time; and (5) indirect comparison of relative treatment effects with other biologics based on Bayesian network meta-analysis. CONCLUSION: The rapid and sustained efficacy of ixekizumab in the treatment of psoriasis was demonstrated using multiple dynamic visualizations with different clinical endpoints. Animated visualizations provided a simpler and more comprehensive understanding of complex data than conventional static figures.
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INTRODUCTION: Psoriasis Area Severity Index (PASI) assessment is complex and time-consuming. A simpler assessment measure more sensitive to changes in symptom severity and predictive of patients' quality of life (Dermatology Life Quality Index, DLQI) is needed. This study aims to evaluate the Optimal Psoriasis Assessment Tool (OPAT) as an alternative to PASI. METHODS: This integrated analysis of three UNCOVER trials (NCT01474512, NCT01597245, and NCT01646177) randomized patients (N = 3866) with moderate-to-severe psoriasis to subcutaneously administered ixekizumab 80 mg Q2W or Q4W, or placebo or etanercept 50 mg Q2W. Pearson correlations were computed for clinical and patient-reported measures with PASI and DLQI. RESULTS: As the correlations with PASI and BSA were high and not much higher when adding severity, body surface area (BSA) was used for the clinical measure. BSA was the main measure influencing OPAT. Week 12 regression analyses results showed that PASI had a higher correlation with BSA combined with patient assessments than with BSA alone. Sensitivity analyses were also completed for PASI 75 and 90. For DLQI, correlations with the combined measures were even stronger than with BSA alone. A comprehensive model selection procedure was conducted, which illustrated that the two-term models are preferred. CONCLUSION: The OPAT is a simple and time-saving alternative to PASI. It can be derived using BSA and patient-reported assessments having strong correlation with PASI and moderate correlation with DLQI.
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BACKGROUND: SDZ-ADL (GP2017; Sandoz GmbH, Austria) is an EMA-/FDA-approved adalimumab biosimilar. The effect of SDZ-ADL on quality of life (QoL) and patient-reported outcomes (PROs) was assessed as part of two phase III studies, one in patients with moderate-to-severe chronic plaque psoriasis (PsO; ADACCESS) and the other in patients with rheumatoid arthritis (RA; ADMYRA). Additionally, ADACCESS included patients with psoriatic arthritis (PsA). METHODS: ADACCESS included 465 patients with PsO, whereas ADMYRA included 353 patients with RA. Both studies evaluated and confirmed equivalent efficacy, similar safety, and immunogenicity of SDZ-ADL with reference adalimumab (ref-ADL). A third of patients underwent multiple (four) treatment switches between study treatments starting at Week 17 (ADACCESS); all patients switched from ref-ADL to SDZ-ADL at Week 24 (ADMYRA). Assessed PROs included Dermatology Life Quality Index (DLQI) and EuroQol five-dimension health status questionnaire (EQ-5D-5L) in ADACCESS, Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) score in ADMYRA, and Health Assessment Questionnaire-Disability Index (HAQ-DI) in both studies. RESULTS: In both studies, baseline scores for all PRO assessments were comparable between the two treatment groups. In ADACCESS, mean DLQI decreased from baseline in both groups, and the mean (standard deviation [SD]) percent reductions from baseline in DLQI were comparable between groups at Week 17 (SDZ-ADL, - 64.5 [80.3]; ref-ADL, - 70.6 [41.7]), which were sustained after the switch at Week 51 ('continued SDZ-ADL,' - 79.7 [36.2]; 'continued ref-ADL,' - 80.8 [44.6]; 'switched to SDZ-ADL,' - 70.7 [32.2]; 'switched to ref-ADL,' - 69.3 [49.6]). In ADACCESS, the proportion of patients with an EQ-5D-5L score of 1 (no problems) increased from baseline for all five dimensions in all treatment groups and was comparable between treatment groups at Week 51. In ADACCESS, in patients with PsA at baseline, mean (SD) HAQ-DI scores decreased from baseline in both treatment groups, and scores were comparable between groups at Week 17 (SDZ-ADL, 0.5 [0.6]; ref-ADL, 0.5 [0.6]) and after switching at Week 51 ('continued SDZ-ADL,' 0.4 [0.5]; 'continued ref-ADL,' 0.4 [0.6]; 'switched to SDZ-ADL,' 0.5 [0.8]; 'switched to ref-ADL,' 0.7 [0.6]). In ADMYRA, proportion of patients achieving HAQ-DI in the normal range (≤ 0.5) was comparable between treatment groups at Week 24 (SDZ-ADL, 37.8%; ref-ADL, 36.3%) and after switching at Week 48 ('SDZ-ADL,' 41.6%; 'ref-ADL/switched to SDZ-ADL,' 40.0%). In ADMYRA, mean FACIT-Fatigue scores increased from baseline in both treatment groups. At Week 24, mean (SD) percent change from baseline in the FACIT-Fatigue scores was 75.4 (135.5) in SDZ-ADL and 73.0 (96.3) in ref-ADL groups; the scores were sustained after switching at Week 48. CONCLUSION: Treatment with SDZ-ADL and ref-ADL resulted in comparable improvements in PROs as well as QoL scores across the three diseases, PsO, PsA, and RA. Switching between SDZ-ADL and ref-ADL had no negative impact on PROs across the reported period. CLINICAL TRIALS. GOV IDENTIFIER: NCT02744755, NCT02016105.
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Antirreumáticos , Artritis Psoriásica , Artritis Reumatoide , Biosimilares Farmacéuticos , Actividades Cotidianas , Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Biosimilares Farmacéuticos/uso terapéutico , Método Doble Ciego , Sustitución de Medicamentos , Humanos , Medición de Resultados Informados por el Paciente , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. In the United States, brodalumab carries a boxed warning about suicidal ideation and behavior; however, no causal association was established between brodalumab and suicides reported during pivotal trials. We have previously reported results from an analysis of 1-year pharmacovigilance data in patients in the United States who took brodalumab, in which the most commonly reported adverse event was psoriasis flare. There were no completed suicides, suicide attempts, or serious fungal infections. Here, we provide a 2-year US pharmacovigilance report. METHODS: This analysis summarizes pharmacovigilance data reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, through August 14, 2019. The most common adverse events listed in the brodalumab package insert (incidence ≥ 1%; arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections) and adverse events of special interest are reported. RESULTS: Data were collected from 2677 patients in the United States who took brodalumab, with an estimated exposure of 1656 patient-years. Arthralgia was the most commonly reported adverse event (73 events; 0.04 events per patient-year). No suicide attempts or completed suicides were reported; there were 25 reports of depression. There were 46 serious infections and no serious fungal infections. One event of Crohn's disease was reported, which led to discontinuation. There were 13 malignancies, with none deemed related to brodalumab. CONCLUSIONS: This pharmacovigilance report supports the safety profile of brodalumab previously reported from long-term analyses of clinical trials and 1-year pharmacovigilance data.
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BACKGROUND: Data for the effect of metabolic syndrome (MetS) on the efficacy and safety of biologic agents for psoriasis treatment are limited. OBJECTIVE: To evaluate long-term tildrakizumab efficacy, drug survival, and safety in patients with psoriasis by baseline MetS status. METHODS: Post hoc analyses of up to 3 years of efficacy data and 5 years of safety data from the phase 3, double-blind, randomized controlled reSURFACE 1 and 2 trial (NCT01722331 and NCT01729754) base and extension studies were conducted for patients receiving continuous tildrakizumab 100 or 200 mg. RESULTS: Of 338 (n = 124/214 in reSURFACE 1/2) and 307 (n = 147/160 in reSURFACE 1/2) patients continuously receiving tildrakizumab 100 and 200 mg, respectively, throughout the studies, 26/44 (21%/21%) and 34/30 (23%/19%) met MetS criteria. Proportions of patients who achieved a 75% improvement in the Psoriasis Area and Severity Index (PASI) in reSURFACE 1/2 were generally comparable among those with versus without MetS at week 52 (tildrakizumab 100 mg, 85%/86% vs 86%/94%; tildrakizumab 200 mg, 76%/87% vs 76%/87%) and through week 148. Results were similar for responders with 90% and 100% improvement in the PASI. Tildrakizumab's safety profile did not vary by MetS status. LIMITATIONS: Small sample size and post hoc analysis limit interpretation. CONCLUSION: Long-term tildrakizumab efficacy and safety were comparable between patients with and without MetS.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Síndrome Metabólico/metabolismo , Psoriasis/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacocinética , Comorbilidad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Psoriasis/diagnóstico , Psoriasis/epidemiología , Psoriasis/metabolismo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.
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Terapias Complementarias/métodos , Fármacos Dermatológicos/administración & dosificación , Dermatología/métodos , Psoriasis/terapia , Academias e Institutos/normas , Administración Cutánea , Terapia Combinada/métodos , Terapia Combinada/normas , Terapias Complementarias/normas , Dermatología/normas , Medicina Basada en la Evidencia/métodos , Medicina Basada en la Evidencia/normas , Fundaciones/normas , Humanos , Educación del Paciente como Asunto/normas , Psoriasis/diagnóstico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Estados UnidosRESUMEN
Background: Metabolic syndrome (MetS) is the most prevalent comorbidity in psoriasis and increases the risk of cardiovascular disease, diabetes, and mortality. Assessment of impacts of biologic therapies on cardiometabolic risk factors are relatively limited. This study evaluated the effect of tildrakizumab on cardiometabolic risk factors in patients with moderate to severe plaque psoriasis and stratified by MetS status. Methods: In this post hoc analysis of reSURFACE 1/2, tildrakizumab 100 and 200 mg were continuously administered to patients with moderate to severe plaque psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Mean and mean percent changes from baseline were assessed for fasting serum glucose, low/high-density lipoprotein-cholesterol, total cholesterol, triglyceride levels, body weight, and blood pressure at week 64/52 for reSURFACE 1 and 2, respectively, in patients with and without MetS. Results: A total of 369 patients in reSURFACE 1 and 2 received continuous tildrakizumab 100 mg and 330 received tildrakizumab 200 mg; 21.4% and 20.3% in reSURFACE 1 and 2, respectively, had MetS. At week 64/52, mean changes in cardiometabolic risk factors from baseline did not significantly differ regardless of MetS status. Numerically larger mean decreases in fasting glucose, triglycerides, and systolic blood pressure following tildrakizumab 100 mg and in systolic and diastolic blood pressure following tildrakizumab 200 mg were observed in patients with MetS relative to those without MetS. Conclusions: Changes in cardiometabolic disease risk factors following tildrakizumab treatment were limited. Risk factors were not increased in patients with MetS vs without MetS. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5337.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Enfermedades Cardiovasculares/epidemiología , Síndrome Metabólico/epidemiología , Psoriasis/tratamiento farmacológico , Adulto , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Factores de Riesgo Cardiometabólico , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/prevención & control , Colesterol/sangre , Comorbilidad , Femenino , Humanos , Subunidad p19 de la Interleucina-23/antagonistas & inhibidores , Subunidad p19 de la Interleucina-23/inmunología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Síndrome Metabólico/inmunología , Persona de Mediana Edad , Psoriasis/complicaciones , Psoriasis/epidemiología , Psoriasis/inmunología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Triglicéridos/sangreAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Monitoreo de Drogas/estadística & datos numéricos , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/farmacocinética , Artralgia/inducido químicamente , Artralgia/epidemiología , Artralgia/inmunología , Depresión/inducido químicamente , Depresión/epidemiología , Depresión/inmunología , Diarrea/inducido químicamente , Diarrea/epidemiología , Diarrea/inmunología , Semivida , Humanos , Farmacovigilancia , Psoriasis/inmunología , Receptores de Interleucina-17/antagonistas & inhibidores , Receptores de Interleucina-17/inmunología , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Importance: Risankizumab selectively inhibits interleukin 23, a cytokine that contributes to psoriatic inflammation. Objective: To evaluate the efficacy and safety of risankizumab vs placebo and continuous treatment vs withdrawal in adults with moderate to severe plaque psoriasis. Design, Setting, and Participants: Multinational, phase 3, randomized, double-blind, placebo-controlled trial conducted from March 6, 2016, to July 26, 2018. A total of 507 eligible patients had stable moderate to severe chronic plaque psoriasis for 6 months or longer, body surface area involvement greater than or equal to 10%, Psoriasis Area and Severity Index (PASI) greater than or equal to 12, and a static Physician's Global Assessment (sPGA) score greater than or equal to 3. Intention-to-treat analysis was conducted. Interventions: Patients were randomized (4:1, interactive response technology) to risankizumab, 150 mg, subcutaneously, or placebo at weeks 0 and 4 (part A1). All patients received risankizumab at week 16. At week 28, patients randomized to risankizumab who achieved an sPGA score of 0/1 were rerandomized 1:2 to risankizumab or placebo every 12 weeks (part B). Main Outcomes and Measures: Co-primary end points for the part A1 phase included proportions of patients achieving greater than or equal to 90% improvement in PASI (PASI 90) and sPGA score of 0/1 at week 16. The PASI measures severity of erythema, infiltration, and desquamation weighted by area of skin involvement over the head, trunk, upper extremities, and lower extremities; scores range from 0 (no disease) to 72 (maximal disease activity). The sPGA assesses average thickness, erythema, and scaling of all psoriatic lesions; scores range from 0 (clear) to 4 (severe), with 0/1 indicating clear or almost clear. Primary and secondary end points in part B included proportion of rerandomized patients achieving an sPGA score of 0/1 at week 52 (primary) and week 104 (secondary). Results: Of 563 patients screened, 507 were randomized to risankizumab (n = 407) or placebo (n = 100). Most patients were men (356 [70.2%]); median age was 51 years (interquartile range, 38-60 years). At week 16, 298 patients (73.2%) in the treatment group vs 2 patients (2.0%) receiving placebo achieved a PASI 90 response, and 340 patients (83.5%) receiving risankizumab vs 7 patients (7.0%) receiving placebo achieved sPGA 0/1 scores (placebo-adjusted differences: PASI 90: 70.8%; 95% CI, 65.7%-76.0%; sPGA 0/1: 76.5%; 95% CI, 70.4%-82.5%; P < .001 for both). At week 28, 336 responders were rerandomized to risankizumab (n = 111) or treatment withdrawal (n = 225). At week 52, the sPGA 0/1 score was achieved by 97 patients (87.4%) receiving risankizumab vs 138 patients (61.3%) receiving placebo. At week 104, the sPGA 0/1 score was achieved by 90 patients (81.1%) receiving risankizumab vs 16 patients (7.1%) receiving placebo (placebo-adjusted differences: week 52: 25.9%; 95% CI, 17.3%-34.6%; week 104: 73.9%; 95% CI, 66.0%-81.9%; P < .001 for both). Rates of treatment-emergent adverse events were similar between risankizumab (186 [45.7%]) and placebo (49 [49.0%]) in part A1 and remained stable over time. Conclusions and Relevance: Risankizumab showed superior efficacy compared with placebo through 16 weeks and treatment withdrawal through 2 years. Risankizumab was well tolerated, with no unexpected safety findings during the 2-year trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02672852.
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Anticuerpos Monoclonales/administración & dosificación , Psoriasis/tratamiento farmacológico , Privación de Tratamiento , Adulto , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Inyecciones Subcutáneas , Subunidad p19 de la Interleucina-23/antagonistas & inhibidores , Subunidad p19 de la Interleucina-23/inmunología , Masculino , Persona de Mediana Edad , Placebos/administración & dosificación , Psoriasis/diagnóstico , Psoriasis/inmunología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years. METHODS: Data were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician's Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported. RESULTS: Of 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted. CONCLUSIONS: The results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245.