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. 2022 Oct 1;158(10):1131-1141.
doi: 10.1001/jamadermatol.2022.2909.

Drug Survival Associated With Effectiveness and Safety of Treatment With Guselkumab, Ixekizumab, Secukinumab, Ustekinumab, and Adalimumab in Patients With Psoriasis

Zenas Z N Yiu  1 , Gabrielle Becher  2 , Brian Kirby  3 , Philip Laws  4 , Nick J Reynolds  5 , Catherine H Smith  6 , Richard B Warren  1 , Christopher E M Griffiths  1 ; BADBIR Study Group
Collaborators, Affiliations

Drug Survival Associated With Effectiveness and Safety of Treatment With Guselkumab, Ixekizumab, Secukinumab, Ustekinumab, and Adalimumab in Patients With Psoriasis

Zenas Z N Yiu et al. JAMA Dermatol. .

Erratum in

  • Errors in Figure 2.
    [No authors listed] [No authors listed] JAMA Dermatol. 2022 Dec 1;158(12):1461. doi: 10.1001/jamadermatol.2022.5056. JAMA Dermatol. 2022. PMID: 36383368 Free PMC article. No abstract available.

Abstract

Importance: Drug survival of biologic therapies for psoriasis is a proxy for longer-term treatment effectiveness and safety. Patient factors that are associated with the survival of each biologic differently (effect modifiers) may inform the decision to choose between biologics.

Objective: To assess the drug survival associated with the effectiveness and safety of commonly used biologics for psoriasis in the UK and Ireland and identify effect modifiers for these biologics and their survival.

Design, setting, and participants: We conducted a prospective cohort study of patients with psoriasis using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2021.

Exposures: Adalimumab, ustekinumab, secukinumab, guselkumab, ixekizumab.

Main outcomes and measures: We conducted a survival analysis and fitted separate flexible parametric models for drug survival as a proxy for effectiveness and safety.

Results: A total of 16 122 treatment courses were included: 6607 (41.0%) in which treatment with adalimumab was initiated, 5405 (33.5%) with ustekinumab, 2677 (16.6%) with secukinumab, 730 (4.5%) with guselkumab, and 703 (4.4%) with ixekizumab. The crude survival functions at year 1 for measures of effectiveness for treatment with adalimumab was 0.81 (95% CI, 0.80-0.82), 0.89 for ustekinumab (95% CI, 0.88-0.89), 0.86 for secukinumab (95% CI, 0.85-0.87), 0.94 for guselkumab (95% CI, 0.92-0.96), and 0.86 for ixekizumab (95% CI, 0.83-0.89). The adjusted survival curves from the multivariable model for effectiveness showed that treatment with guselkumab had the higher survival (adjusted hazard ratio, 0.13; 95% CI, 0.03-0.56) and adalimumab had the lower survival (adjusted hazard ratio, 2.37; 95% CI, 2.03-2.76) compared with ustekinumab. Secukinumab and ixekizumab had similar survival curves over time. Psoriatic arthritis, previous biologic exposure, nail involvement, and ethnicity were effect modifiers for survival in association with treatment effectiveness. The crude survival functions at year 1 for safety were 0.91 for treatment with adalimumab (95% CI, 0.90-0.91), 0.94 for ustekinumab (95% CI, 0.94-0.95), 0.94 for secukinumab (95% CI, 0.92-0.94), 0.96 for guselkumab (95% CI, 0.94-0.98), and 0.92 for ixekizumab (95% CI, 0.89-0.94). Guselkumab, ustekinumab, and secukinumab had similar adjusted survival curves for safety, while adalimumab (adjusted hazard ratio, 1.66; 95% CI, 1.46-1.89) and ixekizumab (adjusted hazard ratio, 1.52; 95% CI, 1.13-2.03) had lower survival compared with ustekinumab.

Conclusions and relevance: The results of this cohort study suggest that guselkumab had the highest drug survival in BADBIR of the included biologics for treatment persistence that was associated with effectiveness, and guselkumab had highest drug survival for safety compared with other biologics except ustekinumab. Psoriatic arthritis, nail involvement, previous biologic exposure, and ethnicity were effect modifiers for biologics and their survival in association with treatment effectiveness. This information on longer-term treatment persistence, safety, and tolerability may help patients and their clinicians make an informed decision to initiate treatment with a biologic therapy.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Becher reported personal fees from UCB, AbbVie, Almirall, UCB, Novartis, Janssen, and Eli Lilly outside the submitted work. Dr Kirby reported grants and personal fees from AbbVie, Almirall, and Janssen and personal fees from Leo, Lilly, Novartis, Amgevita, and UCB outside the submitted work. Dr Laws reported grants from AbbVie, Celgene, and Lilly as well as personal fees from Almirall, Actelion, Janssen, Sanofi, Leo, Novartis, Pfizer, and UCB outside the submitted work. Dr Reynolds reported research support from AbbVie, Boehringer Ingelheim, and Celgene as well as grants from Novartis and PSORT outside the submitted work. Dr Smith reported grants from MRC and Horizon outside the submitted work. Dr Warren reported personal fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Boehringer Ingelheim, Biogen, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, Leo Pharma, Lilly, Novartis, Sanfoi, Sun Pharma, UCB, and Union and grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Novartis, and UCB outside the submitted work. Dr Griffiths reported grants from AbbVie, Amgen, Almirall, Boehringer Ingelheim, Leo Pharma, Anaptysbio, and UCB Pharma as well as personal fees from Janssen, Novartis, GSK, Eli Lilly, Bristol Myers Squibb, and Boehringer Ingelheim during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Overlaid Kaplan-Meier (KM) Survival Curves and the Flexible Parametric Model (FPM) Survival Curves for Discontinuation Associated With Ineffectiveness for All Biologic Cohorts During 2 Years
The FPM curve is calculated using the Stata stpm2 meansurv command, which calculates the population-averaged survival curve in which a predicted survival curve is obtained for each participant and all the survival curves in a population are averaged. Shaded areas represent 95% CIs from the FPM curve. The y-axis starts from 0.70 for presentation clarity purposes.
Figure 2.
Figure 2.. Overlaid Kaplan-Meier (KM) Survival Curves and the Population-Averaged Flexible Parametric Model (FPM) Survival Curves for the Biologic Therapies of First-Line, Second-Line, and Third or Subsequent Lines for Discontinuation Associated With Ineffectiveness During 2 Years
Shaded areas represent 95% CIs from FPM curve. The y-axis starts from 0.60 (A and B) or 0.5 (C) for presentation clarity purposes.
See this image and copyright information in PMC

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