A 60-week Real-world Experience with Guselkumab in Patients with Moderate-to-Severe Plaque Psoriasis Including Patients with Malignancy: A Retrospective Study from Ontario, Canada

Dear Editor, Guselkumab is a fully human monoclonal antibody against the p19 subunit of interleukin (IL-23). It was approved by the US Food and Drug Administration in July 2017 and by Health Canada in May 2019 for the treatment of adult patients with moderate-to-severe plaque psoriasis. The recommended dose for plaque psoriasis is 100 mg administered through subcutaneous (SC) injection at week 0 and after 4 weeks, followed by 100 mg SC injection every 8 weeks thereafter. The approval was based on VOYAGE 1 and VOYAGE 2 phase III trials.[1,2] The long-term efficacy and safety of guselkumab were assessed in clinical trials.[3,4] In this real-world experience study, we conducted a retrospective chart review for adult patients with moderate-to-severe plaque psoriasis treated with guselkumab seen in Hamilton Health Sciences Centre and McMaster University in Canada from June 2019 to December 2022. The study was approved by the Hamilton Integrated Research Ethics Board. Baseline characteristics, previous systemic and biologic therapies, Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA) scores, and adverse effects at week 60 were recorded. One hundred and four patients were included in the study; 61 (59%) were female, and the mean age was 44.1 years [standard deviation = 13.2, Table 1]. Sixty-four patients (62%) had at least one medical comorbidity; the most common were dyslipidemia and hypertension in 33 (32%) and 30 (29%) patients, respectively. Body mass index was missing in the majority of charts. The mean duration of the disease was 10.2 years (range: 3–21). A total of 78 patients (75%) were naïve to biologic agents, and 26 (25%) tried at least one biologic agent in the past. Approximately 65% of patients tried ultraviolet B phototherapy and patients used on average 1.1 conventional systemic oral agents before starting guselkumab. Fourteen (14%) patients had been administered tumor necrosis factor-α inhibitors, 8 (8%) ustekinumab, 8 (8%) IL-17 inhibitors, and 2 (2%) other IL-23 inhibitor biologic therapies previously. Apart from eight patients, all subjects received the approved recommended dose and frequency for plaque psoriasis. Seven patients had their frequency increased to every 6 weeks, and one increased to every 4 weeks due to persistent psoriasis and/or persistent psoriatic arthritis. Two patients used methotrexate concurrently with guselkumab for persistent psoriatic arthritis.Table 1: Demographic and baseline characteristics of patients treated with guselkumabAt week 60, PGA and PASI were available for 79 (76%) and 57 (55%) patients, respectively. Seventy-two of 79 patients (91%) achieved PGA 0/1 at week 60. Specifically, 38 patients (48%) achieved PGA 0, and 34 patients (43%) achieved PGA 1. Fifty (88%) of 57 patients for whom their PASI was available achieved PASI-75 and 40 of 57 (70%) achieved PASI-90 at week 60. More females than males and more biologic naïve than biologic-experienced patients achieved PGA 0 [Figures 1 and 2]. Furthermore, more patients with PGA 2 and 3 at baseline achieved PGA 0 than patients with PGA 4 at baseline.Figure 1: Number of patients achieving physician global assessment scores (0, 1, 2–4) at week 60 based on patient’s gender. PGA: Physician Global AssessmentFigure 2: Number of patients achieving physician global assessment scores (0, 1, 2–4) at week 60 based on previous biologic exposure. PGA: Physician Global AssessmentAdverse events were reported in 29 (28%) patients. Transient injection site redness and headaches were the most common adverse effects reported in 14 (13%) and 4 (4%) patients, respectively. No cardiovascular or serious infectious adverse events were reported. Six patients with previous malignancies in remission including cutaneous melanoma, bladder cancer, colon cancer, papillary thyroid carcinoma, breast cancer, and non-Hodgkin’s lymphoma (NHL) were included in the study. While colon cancer, bladder cancer, NHL, and melanoma were in remission and diagnosed more than 5 years before starting guselkumab, thyroid cancer and breast cancer were in remission and diagnosed 4 and 4.5 years before starting guselkumab treatment, respectively. None of the six patients showed signs of recurrence during the study duration. A recent systematic review showed that treatment with IL-23 inhibitors is not associated with an increased cancer risk.[5] Overall, our study showed no safety concerns up to 60 weeks of treatment with no cases of major cardiovascular events, malignancies, or reactivation of tuberculosis. In this report of real-life experience, guselkumab showed excellent and sustained effectiveness at week 60 reflected by PGA, PASI-75, and PASI-90 scores. Results were similar and comparable to phase-3 trials. In particular, PASI-75 was reached by 87% of our patients at week 60, a percentage close to that observed at week 24 in VOYAGE 1 (91.2%) and VOYAGE 2 (89.1%) and similar to that observed at week 48 in VOYAGE 1 (87.8%).[1,2] The findings confirmed the sustained efficacy of guselkumab at week 60 in real-world experience. Guselkumab also appeared safe in this real-world population, including in patients with history of malignancy. This study was limited by the retrospective design, the relatively small number of patients with malignancy, and possible concomitant use of topical therapy. However, the real-world population is a study strength. For example, our study population differed from the phase 3 clinical trials by including more patients with prior systemic and biologic therapy, more women, and patients with various comorbidities such as malignancy, inflammatory bowel disease, heart failure, mood disorders, and multiple sclerosis. Overall, our study supports the effectiveness, excellent safety, and tolerability of guselkumab in the real world. Financial support and sponsorship Nil. Conflicts of interest The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MAH has been a speaker, advisor, or consultant for Lilly, Galderma, Janssen, Leo, Novartis, Pfizer, Sun Pharma, and Sanofi Genzyme.

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