Stef P Menting1, Emma Coussens2, Mieke F Pouw3, Juul M P A van den Reek4, Linda Temmerman5, Hugo Boonen6, Elke M G J de Jong4, Phyllis I Spuls1, Jo Lambert2. 1. Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 2. Department of Dermatology, Ghent University Hospital, Gent, Belgium. 3. Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands4Sanquin Research and Landsteiner Laboratory, Department of Immunopathology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. 4. Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands. 5. Department of Dermatology, Maria Middelares Hospital, Gent, Belgium. 6. Department of Dermatology, H Hart Ziekenhuis, Mol, Belgium.
Abstract
IMPORTANCE: Adalimumab has proven to be effective in suppressing psoriasis disease activity and is administered in a standard dose. OBJECTIVE: To establish a therapeutic range for adalimumab trough levels in the treatment of plaque-type psoriasis, leading to a more personalized treatment. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, prospective, observational, daily practice cohort study conducted at an academic hospital with affiliated secondary care hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2). Both cohorts included adult patients treated with adalimumab for plaque-type psoriasis. Cohort 1 comprised 73 patients who were being treated with adalimumab for more than 24 weeks until 401 weeks. In cohort 2 (n = 62), serum samples were obtained between weeks 24 and 52 of treatment. INTERVENTIONS: Before the start of adalimumab therapy and at time of serum sampling, Psoriasis Area and Severity Index (PASI) scores were determined. MAIN OUTCOMES AND MEASURES: Adalimumab trough level and PASI score at the time of serum sampling to determine the receiver-operator characteristics analyses and concentration effect curve. RESULTS: By means of receiver-operator characteristics analyses with an area under the curve of 0.756 (SD, 0.046; 95% CI, 0.666-0.847) and a sensitivity of 78% and a specificity of 70%, 3.51 mg/L was established as the lower margin for the therapeutic range. By means of a concentration effect curve, 7 mg/L was established as the upper margin. One-third of patients had an adalimumab trough concentration exceeding 7 mg/L. CONCLUSIONS AND RELEVANCE: A therapeutic range of adalimumab trough levels of 3.51 mg/L to 7.00 mg/L, which corresponds to an optimal clinical effect, was identified. In one-third of patients, it was observed that trough concentrations exceeded the therapeutic window. Based on the established range, a therapeutic algorithm for adalimumab treatment for patients with psoriasis can be developed and validated in a prospective patient cohort. By identifying this range, a step has been taken toward a more rational use of biological therapy in psoriasis. Developing a therapeutic algorithm may lead to less overtreatment of patients and cost savings.
IMPORTANCE: Adalimumab has proven to be effective in suppressing psoriasis disease activity and is administered in a standard dose. OBJECTIVE: To establish a therapeutic range for adalimumab trough levels in the treatment of plaque-type psoriasis, leading to a more personalized treatment. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, prospective, observational, daily practice cohort study conducted at an academic hospital with affiliated secondary care hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2). Both cohorts included adult patients treated with adalimumab for plaque-type psoriasis. Cohort 1 comprised 73 patients who were being treated with adalimumab for more than 24 weeks until 401 weeks. In cohort 2 (n = 62), serum samples were obtained between weeks 24 and 52 of treatment. INTERVENTIONS: Before the start of adalimumab therapy and at time of serum sampling, Psoriasis Area and Severity Index (PASI) scores were determined. MAIN OUTCOMES AND MEASURES: Adalimumab trough level and PASI score at the time of serum sampling to determine the receiver-operator characteristics analyses and concentration effect curve. RESULTS: By means of receiver-operator characteristics analyses with an area under the curve of 0.756 (SD, 0.046; 95% CI, 0.666-0.847) and a sensitivity of 78% and a specificity of 70%, 3.51 mg/L was established as the lower margin for the therapeutic range. By means of a concentration effect curve, 7 mg/L was established as the upper margin. One-third of patients had an adalimumab trough concentration exceeding 7 mg/L. CONCLUSIONS AND RELEVANCE: A therapeutic range of adalimumab trough levels of 3.51 mg/L to 7.00 mg/L, which corresponds to an optimal clinical effect, was identified. In one-third of patients, it was observed that trough concentrations exceeded the therapeutic window. Based on the established range, a therapeutic algorithm for adalimumab treatment for patients with psoriasis can be developed and validated in a prospective patient cohort. By identifying this range, a step has been taken toward a more rational use of biological therapy in psoriasis. Developing a therapeutic algorithm may lead to less overtreatment of patients and cost savings.
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