Long-Term Dose Optimization of Adalimumab via Dose Spacing in Patients with Psoriasis

Abstract

Dose spacing (DS) can be useful for optimizing treatment with biologics in psoriasis patients. However, interval prolongation might increase the production of anti-drug antibodies (ADA) and, therefore, reduce the drug’s effectiveness. The long-term effects of DS with adalimumab in psoriatic patients have not been reported. The goal of our study was to evaluate the long-term follow-up of psoriatic patients after adalimumab DS regarding the clinical course and determination of circulating adalimumab, TNFα levels, and anti-adalimumab antibodies. We retrospectively included seven patients treated with adalimumab for moderate-to-severe psoriasis and benefiting from DS from 2010 to 2021. The dose interval of adalimumab was extended to three weeks for all patients and then to four weeks for three of the seven patients. Adalimumab trough levels, TNFα levels, and ADA against adalimumab were measured. For six of the seven patients, absolute PASI values remained below 3 throughout the follow-up period (median = 8.0 years; range: 1.7–11.5) after DS. All the patients were satisfied with the effectiveness of their treatment regime. Within the follow-up period, an average of 63 doses of adalimumab per patient were spared. The median adalimumab trough levels were 4.7 µg/mL (range: 1.9–12.5). TNFα levels remained under 10 pg/mL (undetectable) in all except one patient. ADA against adalimumab remained negative (<10 µg/mL) during the follow-up in all patients. Our data indicate that therapeutic drug monitoring, including the measurement of trough concentrations and ADA, together with the clinical response and patient’s preference, can be helpful for clinical decision making and treatment optimization in psoriasis.

Dimethyl Fumarate Used as an Effective Treatment for Granuloma Annulare Disseminatum: An Immunohistochemical Case Study

“…Similarly to our study, fumaric acid esters (FAEs) have been proposed as an alternative treatment option in GGA in previous reports [1,4,6]. In our patient, the therapy could be optimized and tapered without relapse of disease, as has already been reported for other systemic therapies [9]. FAEs appear to shift a T-helper-cell 1-directed immune response towards a T-helper-cell 2 type of immune response [1,4,6,10].…”

Dose reduction of biologics in patients with plaque psoriasis: a review

“…Eventually, 14 new articles were included ( Figure 1 ). These articles involved four studies testing DR strategies ( Atalay et al, 2021 ; Atalay et al, 2022b ; Di Altobrando et al, 2022 ; Herranz-Pinto et al, 2023 ), one specifically focusing on the effectiveness of returning to standard dosages when DR failed ( van der Schoot et al, 2022a ), two addressing the safety of DR ( Atalay et al, 2022a ; Benzaquen et al, 2022 ), one evaluating the cost-effectiveness of DR ( Atalay et al, 2020b ), and six investigating the implementation and uptake of DR ( Aubert et al, 2022 ; van der Schoot et al, 2022b ; van Muijen et al, 2022 ; Aubert et al, 2023 ; van der Schoot et al, 2023a ; van der Schoot et al, 2023b ). All four studies testing DR strategies were cohort studies, of which three were prospective and one was retrospective.…”

“…Two out of the 14 included studies focused specifically on the safety of DR in the context of antidrug–antibody (ADA) development in patients on DR. Benzaquen et al (2022) analyzed retrospectively measured serum drug levels and ADA levels of the past 11 years in the blood of patients on DR of adalimumab (Q3W/Q4W) (N = 7). They showed median serum trough levels of 4.7 μg/mL (range 1.9–12.5) after a median period of 18 months of DR. During the 11 years of DR, no patient had developed relevant ADAs against adalimumab; ADA levels remained <10 μg/ml ( Benzaquen et al, 2022 ). Atalay et al (2022a) measured serum drug levels and ADA levels in the blood samples from the study population of the CONDOR trial (N = 118), which were collected during the trial.…”

“…Almost all IL-17 and IL-23 inhibitors were included in studies on the uptake and implementation of DR. In total, 14 articles were included ( Atalay et al, 2020b ; Atalay et al, 2021 ; Atalay et al, 2022a ; Aubert et al, 2022 ; van der Schoot et al, 2022a ; Atalay et al, 2022b ; Benzaquen et al, 2022 ; van der Schoot et al, 2022b ; Di Altobrando et al, 2022 ; van Muijen et al, 2022 ; Aubert et al, 2023 ; van der Schoot et al, 2023a ; van der Schoot et al, 2023b ; Herranz-Pinto et al, 2023 ). Multiple studies were excluded due to uncertainty in the DR strategy studied, induction scheme, or absence of effect measurements, and specifically, cost studies regarding IL-17 and IL-23 inhibitors did not include DR.…”

Case report: Area of focus of management of severe pityriasis rubra pilaris by dose optimization of adalimumab biosimilar in combination with acitretin and montelukast

“…Our patient experienced a PRP exacerbation despite receiving acitretin 25 mg/d and adalimumab biosimilar at the conventional dose of 40 mg biweekly. Previous research has demonstrated the potential for optimizing adalimumab dosage through interval adjustments in psoriasis patients, with dose escalation to a weekly regimen leading to notable enhancements in skin lesions ( 15 ). The leukotriene receptor antagonist montelukast was introduced to stabilize and further improve the condition.…”