Blocking interleukin-17 in psoriasis: Real-world experience from the PsoPlus cohort.

BACKGROUND: Real-world studies on the use of biologics in psoriasis (Pso) are increasing, but still scarce. Trough concentrations (Ct s) of interleukin-17 inhibitors (IL-17i) seem promising for clinical decision-making, but their value in daily practice has yet to be proven. OBJECTIVES: To report on IL-17i effectiveness, treatment modifications and Ct use in our clinic. METHODS: Data were collected from IL-17i-treated Pso patients followed up in the PsoPlus clinic at the Dermatology department, Ghent University Hospital, Belgium. Descriptive statistics and Kaplan-Meier analysis were performed. RESULTS: A total of 111 patients were included, counting for 134 IL-17i courses (secukinumab, ixekizumab, and brodalumab). Fifty-five per cent of the patients were bio-naive prior to IL-17i initiation. During maintenance, merely 97.0% and 77% achieved near-complete and complete skin clearance, respectively. Major reasons for treatment modification were suboptimal response (63.0%) and safety issues (9.3%). Reported modifications were switch (25.4%), dose escalation (11.9%), dose de-escalation (6.7%), treatment association (6.0%) and IL-17i stop (3.0%). Overall drug survival was 69.0 months, without difference between the different IL-17i (p = 0.078). Ixekizumab tended to have the highest survival. Drug survival was higher in bio-naive subjects compared to bio-experienced subjects (p = 0.011). Ct was measured in 20 patients and interpreted post hoc. In 85%, the clinical decision was in accordance with the Ct (e.g. substantiated need for dose escalation). For the other cases, the Ct would have led to another clinical decision if known at that time. CONCLUSIONS: This real-world study showed that IL-17i are very effective drugs for Pso, with ixekizumab as leading biologic. Prior bio-experience seemed to impact IL-17i drug survival. Treatment modifications were mainly performed in case of insufficient response, primarily via switch and dose escalation, and least frequently in ixekizumab patients. Ct might rationalize clinical decision-making; however, there is need for standardized algorithms to corroborate its use.

Therapeutic drug monitoring in dermatology: the way towards dose optimization of secukinumab in chronic plaque psoriasis.

BACKGROUND: Despite the favourable efficacy profile of secukinumab, clinicians encounter varying clinical responses among patients potentially associated with under- and overdosing. As biologics are expensive, their rational use is crucial and evident. Therapeutic drug monitoring could guide clinicians in making decisions about treatment modifications. AIM: In this multicentre, prospective study, we aimed to develop and validate a secukinumab immunoassay and searched for the therapeutic window in patients with psoriasis. METHODS: We determined secukinumab concentrations at trough in sera from 78 patients with psoriasis at multiple timepoints (Weeks 12, 24, 36, 48 and 52; after Week 52, measurements could be taken at an additional three timepoints) during maintenance phase, using an in-house secukinumab immunoassay consisting of a combination of MA-SEC66A2 as capture antibody and MA-SEC67A9, conjugated to horseradish peroxidase, as detecting antibody. At each hospital visit, disease severity was assessed using the Psoriasis Area and Severity Index (PASI). RESULTS: After quantification, 121 serum samples were included for dose-response analysis. Based on a linear mixed-effects model, secukinumab trough concentrations were found to decrease with increasing body mass index (BMI). Based on receiver operating characteristic (ROC) analysis, we concluded that the minimal effective secukinumab threshold was 39.1 mg/L in steady state, and that this was associated with a 92.7% probability of having an optimal clinical response (PASI ≤ 2 or reduction in PASI of ≥ 90%). CONCLUSIONS: Monitoring and targeting a secukinumab trough concentration of 39.1 mg/L may be a viable treatment option in suboptimal responders. In patients with higher BMI, weight-based dosing may be needed in order to prevent underdosing.

Dermatologists on the medical need for therapeutic drug monitoring of biologics in psoriasis: results of a structured survey.

BACKGROUND: Therapeutic drug monitoring (TDM) may lead to more rational use of biologics. Still, TDM is largely underexplored in psoriasis. Little is known about the dosing behavior of biologics by dermatologists, and their attitude toward TDM. OBJECTIVE: Exploration of the awareness and need for the concept of TDM in psoriasis amongst (inter)national dermatologists. METHOD: A survey was distributed at the Belgian Dermatology Days 2019 and Skin Inflammation & Psoriasis International Network (SPIN) Congress 2019. Next, an online survey version was launched amongst the SPIN Scientific Committee members. We collected physician's characteristics, prescription behavior of biologics, data regarding clinical response to biologics and attitude toward TDM. RESULTS: A total of 107 surveys were included for analysis. Most dermatologists were Belgium-based (54.2%), others from European (23.4%) or non-European countries (19.6%). Seventy percent performed either dose increase (64.8%), time interval shortening (74.6%), dose lowering (16.9%) or time interval extension (33.8%). The majority who performed dose adaptations acknowledged the need for TDM. CONCLUSION: This study showed most dermatologists perform dose adaptations empirically. The need for TDM was indicated by the majority, implying the need for effective communication regarding availability, utility and implementation of TDM assays in daily dermatology practice.

Dose reduction of the new generation biologics (IL-17 and IL-23 inhibitors) in psoriasis: study protocol for an international, pragmatic, multicenter, randomized, controlled, non-inferiority study-the BeNeBio study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease for which biologics are effective treatments. Dose reduction (DR) of the first generation biologics seems a promising way for more efficient use of expensive biologics. A substantial part of patients on tumor necrosis factor (TNF)-alfa inhibitors and ustekinumab could successfully lower their dose, after following a tightly controlled DR strategy. The objective of this study is to assess whether controlled DR of interleukin (IL)-17 and IL-23 inhibitors in psoriasis patients with low disease activity is non-inferior (NI) to usual care (UC). METHODS: This is an international, prospective, multicenter, pragmatic, randomized, non-inferiority trial. A total of 244 patients with stable low disease activity (Psoriasis Area and Severity Index (PASI) ≤ 5) for at least 6 months and using secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, or tildrakizumab in the standard dose, together with stable low disease activity, defined as a PASI ≤ 5 and Dermatology Life Quality Index (DLQI) ≤ 5 at the moment of inclusion, will be randomized 2:1 to DR or UC. In the DR group, dosing intervals will be prolonged stepwise to achieve 66% and 50% of the original dose. Disease activity is monitored every 3 months by PASI and DLQI. In case of disease flare (i.e., PASI and/or DLQI increase), treatment is adjusted to the previous effective dose. The primary outcome is the incidence proportion of persistent flares (PASI > 5 for ≥ 3 months), which will be compared between arms. Secondary outcomes include proportion of patients with successful DR, (course of) PASI and DLQI, serious adverse events (SAEs), health-related quality of life, costs, and pharmacokinetic profile. Outcomes of DR will be compared to UC. DISCUSSION: With this study, we aim to assess whether DR of IL-17 and IL-23 inhibiting biologics can be achieved for psoriasis patients with low disease activity, without losing disease control. Reducing the dose may lead to more efficient use of biologics. TRIAL REGISTRATION: ClinicalTrials.gov NCT04340076 . Registered on April 9 2020.