Etanercept An Overview of Dermatologic Adverse Events

Objectives: To provide a comprehensive overview of dermatologic adverse events of etanercept described in the literature (including all study types, case reports, and surveys) and to present information on the occurrence, severity, treatment, and course of these adverse events. Data Sources: MEDLINE and EMBASE. Study Selection: All reports on individual patients who developed a dermatologic adverse event associated with systemic etanercept treatment for any indication in any type of original article were included. Data Extraction: All data were independently extracted by 2 reviewers. Disagreements were resolved by consensus. All articles included (except for case reports/case series) were assessed regarding level of evidence. Data Synthesis: In 126 included study reports, a total of 72 separate specific dermatologic adverse events of etanercept were mentioned. In 101 case reports/case series, 153 individual patients with approximately 65 different specific diagnoses (eg, not rash) were reported. Conclusions: Etanercept is associated with a wide variety of dermatologic adverse events, many of which were described in study reports, but case reports also described numerous exceptional cases. Although the adverse events are usually mild, some reactions are serious and even potentially life threatening. Therefore, all drug-associated cutaneous abnormalities should be carefully evaluated. Diagnostic steps do not deviate from the norm in these patients, but management of the dermatologic adverse events may need special attentio

Extent and Consequences of Antibody Formation Against Adalimumab in Patients With Psoriasis One-Year Follow-up

IMPORTANCE In a previously reported cohort of 29 patients with plaque-type psoriasis followed up for 24 weeks, clinically relevant antidrug antibody (ADA) to adalimumab was frequently found. Long-term data were lacking. We now present the extension of this study: 80 patients followed up for 1 year. OBJECTIVES To assess the extent of ADA and its clinical consequences after 24 weeks of adalimumab treatment for psoriasis in a cohort of 80 patients. DESIGN, SETTING, AND PARTICIPANTS A multicenter cohort study, performed in the outpatient dermatology clinic of 2 academic hospitals, included 80 sequential patients receiving adalimumab therapy for plaque-type psoriasis and had a follow-up of 1 year. Outcome assessors were not aware of the presence of antibodies to adalimumab or the adalimumab serum concentration when assessing patients' Psoriasis Area and Severity Index (PASI), and personnel analyzing serum samples were blinded to patients' PASI. INTERVENTIONS For 80 patients treated with adalimumab for psoriasis, disease severity (PASI) was assessed, blood samples were collected, and adalimumab and ADA concentrations was determined at baseline and at weeks 12, 24, and 52. MAIN OUTCOMES AND MEASURES Patient PASI and adalimumab and ADA concentrations. RESULTS Antidrug antibody formed in 49% of patients, before week 24 in 90% of them. Adalimumab and ADA concentrations, clinical response and ADA concentration, and adalimumab concentration and clinical response had correlations of -0.872, -0.606, and 0.519, respectively. The adalimumab dose interval was shortened because of lack of efficacy in 15 patients, 7 with and 8 without ADA; improvement in responder status occurred in 1 of 7 and 4 of 8, respectively. CONCLUSIONS AND RELEVANCE Patients with no ADA formation in the first 24 weeks of treatment have little chance of it in the following 24 weeks. The presence of ADA is strongly correlated with adalimumab concentration and greatly influences clinical response. If ADA is present, dose interval shortening is less usefu

How good are clinical severity and outcome measures for psoriasis: Quantitative evaluation in a systematic review

A large number of clinical measures of psoriasis are used in clinical trials and daily practice. These measures lack uniformity and validation. However, valid outcome and severity measures for psoriasis are a prerequisite for fully informative clinical research and evidence-based medicine. The purpose of this study was to identify all clinical measures of psoriasis severity and outcome in use and to evaluate the quality of these measures using clinimetric criteria; we identified 53 separate clinical measures, which were regrouped into 11 measures for quality analysis. No measure could be scored on all items used in the clinimetric analysis. The Lattice System Physician's Global Assessment and Physician's Global Assessment were most highly noted. We conclude that none of the psoriasis measures is adequately validated. The Psoriasis Area and Severity Index is the most commonly used clinical measure in research, but it has substantial limitations such as low response distribution, no consensus on interpretability, and low responsiveness in mild disease. Nevertheless, because of its widespread use the Psoriasis Area and Severity Index permits some degree of comparison of results among clinical trials. Overall, no best instrument was identified, and different situations may call for different measures

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis

Abstract Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, setting, and participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main outcomes and measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients with Psoriasis

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.