Developing a Therapeutic Range of Adalimumab Serum Concentrations in Management of Psoriasis: A Step Toward Personalized Treatment.

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.

• Authors: Stef P Menting, Emma Coussens, Mieke F Pouw, Juul M P A van den Reek, Linda Temmerman, Hugo Boonen, Elke M G J de Jong, Phyllis I Spuls, Jo Lambert
• Journal: JAMA dermatology (JAMA Dermatol) Vol. 151 Issue 6 Pg. 616-22 (Jun 2015) ISSN: 2168-6084 [Electronic] United States
• PMID: 25807311 (Publication Type: Journal Article, Multicenter Study)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal, Humanized
• Adalimumab

Topics

• Adalimumab
• Adult
• Algorithms
• Anti-Inflammatory Agents (blood, therapeutic use)
• Antibodies, Monoclonal, Humanized (blood, therapeutic use)
• Belgium
• Cohort Studies
• Female
• Humans
• Male
• Middle Aged
• Netherlands
• Precision Medicine (methods)
• Prospective Studies
• Psoriasis (drug therapy, pathology)
• Sensitivity and Specificity
• Severity of Illness Index
• Time Factors
• Treatment Outcome