Real-world Data Reveal Long Drug Survival for Guselkumab in Patients with Plaque Psoriasis

Marloes E. van Muijen1,2, Sarah E. Thomas1,2, Douwe Vellinga3, Silke Bouwman4, Martijn B. A. van Doorn5, Klaziena Politiek6, Marisol E. Otero1,2, Juul M. P. A. van den Reek1,2, Elke M. G. J. de Jong1,2,7 and the BioCAPTURE consortium

1Department of Dermatology and 2Radboud Institute for Health Sciences, Radboud University Medical Centre, Geert Grooteplein Zuid 10, Postbus 9101, NL-6525 GA Nijmegen, Departments of Dermatology: 3Alrijne Ziekenhuis, Leiderdorp, 4University Medical Centre Groningen, Groningen, 5Erasmus University Medical Centre, Rotterdam and 6Medisch Centrum Leeuwarden, Leeuwarden, and 7Radboud University, Nijmegen, The Netherlands. E-mail: Marloes.vanMuijen@radboudumc.nl

Accepted Jul 5, 2022; Epub ahead of print Jul 5, 2022

Acta Derm Venereol 2022; 102: adv00755. DOI: 10.2340/actadv.v102.685

Guselkumab has been registered as the first interleukin-23 (IL-23) inhibitor for treatment of psoriasis. Randomized controlled trials (RCTs) have shown a favourable efficacy and safety profile for guselkumab (1, 2). However, RCTs may not adequately reflect the real-world situation (3). The primary objective of this real-world observational multicentre study was to evaluate 1- and 2-year drug survival (DS) of guselkumab, split for discontinuation due to ineffectiveness or side-effects. A further aim was to elucidate predictors for a shorter guselkumab DS.

METHODS AND RESULTS

A detailed description of the methods is given in Appendix S1. Data from patients with plaque psoriasis treated with guselkumab were collected from the prospective BioCAPTURE registry (www.biocapture.nl) and retrospective data from 4 other centres in the Netherlands (time-frame 2020 to 2021). Temporary treatment interruptions for any reason were allowed if <90 days. This 90-day gap was prolonged up to 1 year if patients discontinued due to fear of COVID-19 or due to remission. In the Kaplan–Meier analyses, 3 separate DS curves were created with an event for discontinuation in general (all reasons), due to ineffectiveness or to side-effects. Discontinuation due to an increase in musculoskeletal complaints in patients with psoriatic arthritis (PsA) was considered as an event in side-effect analyses. Univariable and multivariable Cox regression models were used to identify factors affecting DS.

Participating centres and patient and treatment characteristics are shown in Tables SI and SII, respectively. A total of 195 patients (288.4 actively-treated patient years) were included; 110 (56.4%) were male, and 58 (29.7%) were biologic naive at guselkumab initiation. Forty (20.5%) patients had a rheumatologist-confirmed diagnosis of PsA. Six (3.1%) patients shortened the dosing interval, and 27 (13.8%) lengthened the interval.

Overall guselkumab DS rates after 1 and 2 years were 85.5% and 77.8%, respectively. One- and 2-year DS rates for discontinuation related to ineffectiveness were 92.8% and 88.7%, and for discontinuation related to side-effects were 94.3% and 92.1%, respectively (Fig. 1). The outputs of the Cox regression analyses are shown in Table SIII.

The multivariable model showed a significant association between diabetes mellitus type 2 (DMt2) and a shorter DS (hazard ratio (HR) 3.69 (95% confidence interval (95% CI) 1.14–11.98) (p = 0.030) due to ineffectiveness. Multivariable analyses for predictors of side-effect-related DS showed a significant association for a shorter DS in patients with PsA (HR 7.51 (95% CI 2.26–24.95) (p = 0.001)).

DISCUSSION

This study shows that 1- and 2-year DS for guselkumab was high, both for discontinuation due to side-effects and ineffectiveness. The latter finding is notable, as in previous literature higher discontinuation rates due to ineffectiveness have been described for other types of biologics (4). Previous studies on guselkumab DS in real-world settings have also reported high first-year DS (ranging from 68.0% (5) to 95.0% (6)), although sample size was often small, and the event definition and duration of follow-up varied (5–11).

A substantial number of patients in this study (n = 27, 13.8%) used a lengthened dosing interval, which suggests that, for guselkumab, high therapeutic effectiveness can be maintained even on a lower dose. In ongoing studies on guselkumab for psoriasis, the use of a prolonged dosing interval is currently being evaluated (12, 13).

Having PsA was associated with a shorter DS due to side-effects. It should be noted that the association between side-effect-related discontinuation and PsA was largely explained by patients with pre-existent PsA who experienced an increase in musculoskeletal complaints. In contrast, a systematic review on predictors of persistence for other biologics, described having PsA as predictive for longer survival (14). Furthermore, we found an association between DMt2 and a higher risk of discontinuation due to ineffectiveness. In support of our findings, the Corrona psoriasis registry has previously reported that diabetes reduced the risk of achieving various biologic treatment goals (15).

A strength of this study is the large study population, and high external validity due to the multicentre design. Due to the COVID-19 pandemic, there were fewer clinical visits during the study period and more treatment interruptions due to fear of COVID-19. These interruptions were handled differently (see Appendix S1), leading to a more realistic reflection of DS in non-COVID-19 time-frames.

In conclusion, this study found a high 1- and 2-year DS for guselkumab. Reassuringly, discontinuation due to ineffectiveness or side-effects was very uncommon. Having DMt2 was associated with a shorter DS due to ineffectiveness, whereas having PsA was associated with a shorter DS due to side-effects. A substantial proportion of patients (14%) was able to prolong their dosing interval.

ACKNOWLEDGEMENTS

The authors would like to thank Eldrid Schoonhoven, Janneke Huizinga and Barbara Horváth for their contribution to data entry.

Conflicts of interest: MEvM carries out clinical trials for AbbVie, Celgene, Janssen and Novartis, and has received a speaking fee from Janssen. All funding is not personal, but goes to the independent Research Fund of the Department of Dermatology of the Radboud University Medical Centre Nijmegen (Radboudumc), The Netherlands. DV carried out clinical trials for Novartis and attended advisory boards from AbbVie, Almirall, Janssen, Novartis, Leo Pharma and UCB. MBAvD has received consulting fees or honorarium from Novartis, AbbVie, Pfizer, Leo Pharma, Sanofi, Lilly, Janssen and Celgene, has received a grant and payment for lectures including service on speakers bureaus from Novartis, Sanofi and Janssen.KP has attended advisory boards for Sanofi, Leo Pharma and AbbVie, and has received reimbursement for organizing a symposium from AbbVie. MEO has acted as consultant for Lilly. SRPD has attended advisory boards for AbbVie, Janssen and Leo Pharma, and has received a congress fee from AbbVie. RAT has attended advisory boards from Leo Pharma, Lilly, and Novartis. PPMvL has received funding from Wyeth for research and carried out clinical trials for Abbott and Janssen. P. P. M. van Lümig has received speaking and consulting fees from Wyeth and Schering-Plough and has received reimbursement for attending a symposium from Schering-Plough and Pfizer. P. P. M. van Lümig has attended advisory boards for AbbVie, Leo Pharma, Novartis and UCB. JMPAvdR carried out clinical trials for AbbVie, Celgene and Janssen and has received speaking fees/attended advisory boards from AbbVie, Janssen, BMS, Almirall, LEO Pharma, Novartis, UCB and Eli Lilly and reimbursement for attending a symposium from Janssen, Pfizer, Celgene and AbbVie. All funding is not personal, but goes to the independent research fund of the Department of Dermatology of Radboudumc Nijmegen, the Netherlands. EMGJdJ has received research grants for the independent research fund of the department of dermatology of the Radboudumc Nijmegen, the Netherlands from AbbVie, Novartis, Janssen Pharmaceutica and Leo Pharma. Has acted as consultant and/or paid speaker for and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis including AbbVie, Janssen Pharmaceutica, Novartis, Lilly, Celgene, Leo Pharma, UCB and Almirall. All funding is not personal, but goes to the independent research fund of the Department of Dermatology of Radboudumc, Nijmegen, the Netherlands.

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