Real-world Performance of a New Strategy for Off-Label Use of Guselkumab in Moderate to Severe Psoriasis: Super-Responder Patients as the Epitome of Efficacy and Optimisation

Pinto, Pedro Herranz; Alonso‐Pacheco, M.L.; Feltes, Rosa; Mayor-Ibarguren, Ander; Servera-Negre, Guillermo; Busto-Leis, Jose Manuel; González-Fernández, María Ángeles; Herrero-Ambrosio, Alicia

doi:10.1007/s40261-023-01280-9

Cited by 7 publications

(19 citation statements)

References 77 publications

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…The third prospective cohort study was by Di Altobrando et al (2022 ), in which a total of 199 patients started a reduced dose (N = 96/199) or continued a standard dose (N = 103/199) of either adalimumab, etanercept, infliximab, or ustekinumab for maximal of ±102 months. Herranz-Pinto et al (2023) performed a retrospective cohort study with a total of 69 patients, who started a reduced dose (N = 45/64) or continued the standard dose (N = 24/69) of guselkumab and were observed for a maximum of 90 weeks. Some studies were found in which a DR strategy of secukinumab, ixekizumab, brodalumab, and tildrakizumab was tested but were eventually excluded due to an uncertainty of which DR strategies were studied, whether an induction scheme was followed or not, or because DR was applied from the start of biologic use, or because results did not include effect measurements.…”

Section: Resultsmentioning

confidence: 99%

“…The eligibility criteria used to start DR in the four pre-mentioned studies were roughly divided into two types: (i) the treatment duration of the biologic used in the standard dose prior to DR and (ii) the effectiveness of the biologic used in the standard dose at the moment of considering DR. In the 4 included studies, the treatment duration prior to DR ranged from ≥150 days ( Herranz-Pinto et al, 2023 ) to ≥6 months ( Atalay et al, 2021 ; Atalay et al, 2022b ) to ≥1 year prior to DR ( Di Altobrando et al, 2022 ). The effectiveness of the biologic used in the standard dose was determined by scoring the disease activity or state of clinical remission by using the absolute and/or relative PASI.…”

Section: Resultsmentioning

confidence: 99%

“…The precise cut-off values of PASI varied between studies; however, all studies required low disease activity or a specific state of clinical remission for a certain period. Di Altobrando et al (2022) chose a relative PASI 75–100 for ≥1 year, Herranz-Pinto et al (2023) chose a complete response after 12 weeks (relative PASI 100), and both studies by Atalay et al (2021) and Atalay et al (2022b) used a PASI ≤5 for ≥6 months. Only the studies by Atalay et al (2021) ; Atalay et al (2022b) included the quality of life as an additional eligibility criterion, which was defined as a DLQI score of 5 or lower.…”

Section: Resultsmentioning

confidence: 99%

“…In the study by Di Altobrando et al (2022) , DR was also performed by fixed interval prolongation in one step but with different percentages of the standard dose ranging from 67% (adalimumab every 3 weeks and etanercept every 10 days) to 80% (infliximab every 10 weeks) to 86% (ustekinumab every 14 weeks). In the study by Herranz-Pinto et al (2023) , DR was performed by interval prolongation on-demand and showed that doses ranged from 73% (guselkumab every 11 weeks) to 47% (guselkumab every 17 weeks) to 30% (guselkumab every 27 weeks) of the standard dose. The studies included in the previous review applied DR by either interval prolongation or lowering the administration dose ( Table 1 ) ( Michielsens et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

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

van Riel,

Michielsens,

van Muijen

et al. 2024

Front. Pharmacol.

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Dose reduction (DR) of first-generation biologics for plaque psoriasis (TNF-alpha inhibitors (i) and interleukin (IL)-12/23i) has been described in a previous scoping review. The literature on the DR of the newest generation of biologics (IL-17/23i) was scarce. The current review provides a literature update on the previous scoping review on the DR of all biologics, including the newest generation, with a focus on the uptake and implementation of DR in practice. The current literature search on DR revealed 14 new articles in addition to those in the previous review. Four of the newly found articles tested DR strategies, mostly focusing on first-generation biologics; only guselkumab (IL-23i) was included in one study. The other 10 studies showed data on regaining response after failure of DR, safety, cost-effectiveness, and uptake and implementation, as well as information about IL-17/23i. The eligibility criteria to start DR included both absolute and relative Psoriasis Area and Severity Index (PASI) scores (PASI ≤3/≤5/PASI 75–100) and/or Dermatology Life Quality Index (DLQI) ≤3/≤5, or BSA ≤1/≤2, or Physician Global Assessment (PGA) ≤1/0–2 during a period ranging from 12 weeks to ≥1 year. Most studies used PASI ≤5 and/or DLQI ≤5 or PGA ≤1 for ≥6 months. DR strategies were mostly performed by stepwise interval prolongation in two steps (to 67% of the standard dose, followed by 50%). Some studies of IL-17/23i reduced the dose to ±25%. The tested DR strategies on stepwise or fixed DR on TNF-αi and IL-12/23i (three studies), as well as one “on-demand” dosing study on IL-23i guselkumab, were successful. In the case of relapse of DR on TNF-αi and IL-12/23i, clinical effectiveness was regained by retreatment with the standard dose. All studies showed substantial cost savings with the biologic DR of TNF-αi and IL-12/23i. The identified barriers against the implementation of DR were mainly a lack of guidelines and scientific evidence on effectiveness and safety, and a lack of time and (technical) support. The identified facilitators were mainly clear guidelines, feasible protocols, adequate education of patients and physicians, and cost reduction. In conclusion, DR seems promising, but a research gap still exists in randomized, prospective studies testing DR strategies, especially of IL-17/23i, hampering the completion of guidelines on DR. Taking into account the identified barriers and facilitators most likely results in a more successful implementation of biologic DR in practice.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

van Riel,

Michielsens,

van Muijen

et al. 2024

Front. Pharmacol.

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Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis

Eyerich,

Asadullah,

Pinter

et al. 2024

JAMA Dermatol

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ImportancePsoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies.ObjectiveTo evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis.Design, Setting, and ParticipantsThe GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis. In study part 2, reported herein, first and last patient visits were September 2019 and March 2022, respectively.InterventionsIn GUIDE part 1 (week [W]0-W28), patients received guselkumab, 100 mg, at W0, W4, W12, and W20. Those achieving a Psoriasis Area and Severity Index (PASI) of 0 at both W20 and W28 were termed super responders (SRes). In part 2 (W28-W68), SRes were randomized to guselkumab, 100 mg, every 8 weeks or every 16 weeks; non-SRes continued open-label guselkumab every 8 weeks.Main Outcomes and MeasuresPrimary objective was to demonstrate noninferiority (with a 10% margin) of guselkumab every 16 weeks vs every 8 weeks dosing among SRes for maintenance of disease control (PASI &lt;3 at W68). Biomarker substudies assessed immunologic effects in skin and blood.ResultsOverall, 822 patients received guselkumab in part 2 (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). Among SRes, mean (SD) age was 39.4 (14.1) years, 95 (32.0%) were female, and 202 (68.0%) were male. The primary end point of noninferiority for guselkumab every 16 weeks vs every 8 weeks in SRes was met (P = .001), with 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes receiving every 16 weeks and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes receiving dosing every 8 weeks having PASI lower than 3 at W68. Clinical effects corresponded with immunologic changes; skin CD8-positive tissue-resident memory T (TRM)–cell count decreased quickly from baseline, remaining low in both dosing groups. Similarly, serum IL-17A, IL-17F, IL-22, and β defensin (BD)–2 levels decreased significantly from baseline, remaining low in both dosing groups to W68. Guselkumab was well-tolerated; no new safety signals were identified.Conclusions and RelevancePsoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation. We present the first randomized trial providing evidence that, in patients with early complete skin clearance at 2 consecutive visits (W20 and W28), extending the guselkumab dosing interval may control disease activity.Trial RegistrationClinicalTrials.gov Identifier: NCT03818035

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Drug Survival of IL-17 and IL-23 Inhibitors for Psoriasis: A Systematic Review and Meta-Analysis

Thomas,

Barenbrug,

Hannink

et al. 2024

Drugs

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Background and Objective The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to assess drug performance in practice. An overview of the available drug survival studies regarding IL-17 and IL-23 inhibitors is lacking. Therefore, our objective was to assess the drug survival of IL-17 and IL-23 inhibitors for psoriasis. Methods A search of PubMed, Embase, Cochrane Library and Web of Science was conducted (last search 27 December, 2023). Inclusion criteria were (1) cohort study; (2) patients aged ≥ 18 years with plaque psoriasis; and (3) evaluation of drug survival of at least one of the IL-17 and IL-23 inhibitors. Exclusion criteria were: primary focus on patients with psoriatic arthritis, fewer than ten study subjects and another language than English. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Survival probabilities at monthly intervals were extracted from Kaplan–Meier curves using a semi-automated tool. Data were pooled using a non-parametric random-effects model to retrieve distribution-free summary survival curves. Summary drug survival curves were constructed per biologic for different discontinuation reasons: overall, ineffectiveness and adverse events, and split for the effect modifier biologic naivety. Results were analysed separately for registry/electronic health record data and for pharmacy/claims data. Results A total of 69 studies aggregating drug survival outcomes of 48,704 patients on secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, and tildrakizumab were included. Summary drug survival estimates of registry/electronic health record studies for overall, ineffectiveness and adverse event related drug survival were high (all point estimates ≥ 0.8 at year 1) for included biologics, with highest estimates for guselkumab and risankizumab. All estimates for drug survival were higher in biologic naive than in experienced patients. Estimates of pharmacy/claims databases were substantially lower than estimates from the primary analyses based on registry/electronic health record data. Conclusions This meta-analysis showed that the investigated IL-17 and IL-23 inhibitors had high drug survival rates, with highest rates for guselkumab and risankizumab drug survival. We showed that effect modifiers such as biologic naivety, and the source of data used (registry/electronic health record data vs pharmacy/claims databases) is relevant when interpreting drug survival studies. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-024-02028-1.

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Real-world Performance of a New Strategy for Off-Label Use of Guselkumab in Moderate to Severe Psoriasis: Super-Responder Patients as the Epitome of Efficacy and Optimisation

Cited by 7 publications

References 77 publications

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

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

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis

Drug Survival of IL-17 and IL-23 Inhibitors for Psoriasis: A Systematic Review and Meta-Analysis

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