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.

Evaluation of a One-step Dose Reduction Strategy of Adalimumab, Etanercept and Ustekinumab in Patients with Psoriasis in Daily Practice.

Dose reduction of biologics for psoriasis could contribute to lower drug exposure. This study evaluated a one-step, tightly controlled, biologic dose reduction strategy in a prospective daily practice cohort. In patients with psoriasis with low disease activity using adalimumab, etanercept or ustekinumab for at least 6 months, the dosing interval was prolonged with 33%. Patients could return to their normal dosing interval in case of disease flare. Of 108 eligible patients, 80 started dose reduction and were analysed. In total, 36/80 patients (45.0%) discontinued dose reduction after 19 months (95% confidence interval 14.9-23.1 months). Of 67 patients with 1-year follow-up, 45 (67.2%) still used the lower dose after 1 year. No serious adverse events related to dose reduction occurred. Cumulative dose and costs decreased by 22.7% during 1 year. In conclusion, a one-step tightly controlled dose reduction strategy for adalimumab, etanercept and ustekinumab has considerable potential to safely decrease biologic dosages in patients with psoriasis in daily practice.

Effectiveness and Safety of Systemic Therapy for Psoriasis in Older Adults: A Systematic Review.

Importance: Treating older adults with psoriasis can be challenging owing to comorbidities, concomitant medication use, and consequent safety risks. Although many studies focus on the effectiveness and safety of systemic antipsoriatic therapies in the general population, their effectiveness in older adults with psoriasis has not been systematically assessed. Objective: To evaluate the effectiveness and safety of systemic antipsoriatic therapies in patients 65 years or older. Evidence Review: A systematic literature search was conducted in Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) on November 11, 2019. No date limit was used. Randomized clinical trials, cohort studies, large case series, and meta-analyses assessing efficacy (or effectiveness) and/or safety of systemic antipsoriatic therapies in patients 65 years or older were included. Findings: The initial search yielded 11 096 results, of which 31 unique articles with 39 561 patients were included in analysis. Overall, limited data were available per systemic agent, and overall quality of the included studies on conventional systemic therapies was low. At the end of the induction phase (12-16 weeks after start of treatment), a reduction of 75% in Psoriasis Area and Severity Index was achieved in 49% of 74 methotrexate sodium users 65 years or older, 46% to 52.6% of 178 older cyclosporin users, 27% to 47.8% of 108 older acitretin users, 15.6% to 64% of 256 etanercept users 65 years or older, 66.7% to 93% of 43 infliximab users 65 years or older, 60.7% to 65% of 100 adalimumab users 65 years or older, 56.5% of 46 ustekinumab users 65 years or older, and 86.4% of 67 secukinumab users 65 years or older. Effectiveness of acitretin, etanercept, adalimumab, and secukinumab appeared not to be associated with age; studies regarding other systemic antipsoriatic therapies did not provide age group comparisons. Older age was significantly associated with renal function deterioration in cyclosporin users and with lymphopenia in fumaric acid esters users (hazard ratio, 2.42; 95% CI, 1.65-3.55; P < .001). Infections were the most frequently reported adverse event in patients 65 years or older using biologics, but no significant association with age was found. Conclusions and Relevance: On the basis of limited available evidence, age alone should not be a limiting factor in psoriasis management. Awareness of comorbidities and concomitant medication use is very important, as well as appropriate dosing and frequent laboratory and clinical monitoring. More real-world evidence and (sub)analyses of prospective cohort studies on the effectiveness and safety of systemic therapies in older adults are critical to optimize personalized, effective, and safe antipsoriatic management in this growing patient group.