Guselkumab Provides Relief For Patients Who Suffer With Psoriasis
Overview
A 52-week postmarketing surveillance study was launched to assess the safety and effectiveness of guselkumab, a human monoclonal antibody targeting the interleukin-23 subunit p19, in Japanese patients diagnosed with psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis in real-world clinical settings. This summary presents the findings from the 20-week interim analysis of the ongoing surveillance. The study included patients who began receiving guselkumab between May 2018, following its commercial release in Japan, and October 2020. A total of 411 patients were analyzed for safety, while 245 were included in the effectiveness evaluation.
Adverse drug reactions (ADRs) were reported in 6.6% of patients (27 out of 411), with serious ADRs occurring in 2.2% (nine out of 411). The most common ADRs fell under the “Infections and Infestations” category (2.4%), with nasopharyngitis being the most frequently reported at 0.7%. The Psoriasis Area Severity Index (PASI) score showed a significant reduction, decreasing from an average of 11.6 at the beginning of the study to 6.5 at week 4, and further to 2.2 by week 20, with improvements reaching statistical significance at each time point. Additionally, there were notable improvements in the Clinical Global Impression, Dermatology Life Quality Index, and Nail Psoriasis Severity Index scores.
These findings indicate that guselkumab is both well-tolerated and effective in treating Japanese patients with psoriasis over a 20-week period in a real-world clinical context, with significant improvements observed as early as 4 weeks into treatment. This study is officially registered with the University Hospital Medical Information Network Clinical Trials Registry under the identifier UMIN000032969.
Introduction
Psoriasis is a chronic, immune-mediated skin disease that can lead to negative health outcomes, especially in advanced stages where it is often associated with various comorbidities that further diminish patients’ quality of life. Traditional treatments for psoriasis include topical medications, oral immunosuppressants, and phototherapy. Recently, therapeutic options have expanded to include over ten biologics targeting different cytokines, as well as new small-molecule drugs such as phosphodiesterase-4, Janus kinase, and tyrosine kinase 2 inhibitors, which address the cytokine-driven inflammation characteristic of psoriasis.
In Japan, biologics were first introduced in 2010 with infliximab and adalimumab, both targeting tumor necrosis factor α (TNF-α). This was followed in 2011 by ustekinumab, which targets the interleukin 12/IL-23 subunit 40 (IL-p40). Since 2015, a range of other biologics has become available, including secukinumab, ixekizumab, brodalumab, guselkumab (GUS), risankizumab, tildrakizumab, certolizumab pegol, and bimekizumab. These therapies provide patients and healthcare providers with a broader array of treatment choices for managing psoriasis.
According to guidelines from the Japanese Dermatological Association (JDA), it is crucial for physicians to carefully select the most suitable biologic therapy for each patient, considering disease-specific factors, treatment attributes, and patient background. The JDA guidelines emphasize the importance of evaluating a biologic’s effectiveness, including the likelihood of a high-level response, speed of onset, effectiveness against psoriatic arthritis, and rates of treatment failure. Additionally, considerations include safety concerns, such as infection risks, potential for exacerbating comorbidities, convenience for the patient, and associated medical costs.
Guselkumab, a fully human IgG1λ monoclonal antibody targeting the p19 subunit of IL-23 (IL-23p19), has demonstrated both efficacy and a favorable safety profile in the treatment of psoriasis in previous clinical trials. Approved in Japan in 2018, GUS is indicated for patients with psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis who have not responded adequately to conventional therapies. A post-marketing surveillance (PMS) study, mandated by the Pharmaceuticals and Medical Devices Agency (PMDA) as part of the Risk Management and Pharmacovigilance Plans, is being conducted to evaluate the safety and effectiveness of GUS in real-world clinical settings over a 52-week period. This report presents findings from a 20-week interim analysis of this ongoing PMS study.
While randomized controlled trials are often considered the gold standard for assessing new treatments, the strict inclusion and exclusion criteria used in such trials can result in study populations that do not accurately reflect real-world patients, who may have comorbidities and take other medications concurrently. As a result, real-world studies are increasingly recognized as vital for providing evidence on treatment safety and effectiveness in everyday clinical practice.
This interim analysis offers important insights into the characteristics of Japanese patients receiving GUS for psoriasis in routine clinical practice and provides early data on the safety and effectiveness of GUS. These findings are expected to contribute to ongoing discussions about the optimal use of biologics for psoriasis treatment in Japan.
Methods
This study is a multicenter, single-arm, prospective, observational longitudinal cohort conducted in Japan, focusing on patients with Psoriasis Vulgaris (PsV), Psoriatic Arthritis (PsA), Generalized Pustular Psoriasis (GPP), and Erythrodermic Psoriasis (EP) who began treatment with Guselkumab (GUS). The study spans 52 weeks, following patients from their initial dose of GUS, administered subcutaneously at 100 mg at weeks 0 and 4, followed by maintenance doses every 8 weeks. The protocol was reviewed and approved by internal review boards and the Pharmaceutical and Medical Devices Agency (PMDA). The study complies with the Japanese Ministry of Health, Labour, and Welfare’s Good Post-Marketing Study Practice guidelines, as specified in Ministerial Ordinance no. 171. It commenced after establishing contracts between participating institutions and Janssen Pharmaceutical KK in Tokyo, Japan.
This interim report covers a 20-week period, presenting data from patients who initiated GUS treatment between May 2018 and October 2020. Throughout the observation period, patient demographic data, medical histories, comorbidities, treatment details, and information on concomitant medications were collected. Investigators recorded adverse events (AEs), serious adverse events (SAEs), adverse drug reactions (ADRs), and serious ADRs (SADRs). AEs were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) version 25.0. The study identified serious infections and hypersensitivity reactions as “important identified risks” and classified malignancy, decreased neutrophil count, and major adverse cardiovascular events as “important potential risks” under the Risk Management Plan for GUS.
Statistical Analysis
Effectiveness was measured using the Psoriasis Area Severity Index (PASI), Clinical Global Impression (CGI) scale, Dermatology Life Quality Index (DLQI), and Nail Psoriasis Severity Index (NAPSI). Safety and effectiveness analyses were conducted on respective analysis sets, with exclusions for protocol violations and incomplete or invalid data. Changes in PASI, DLQI, and NAPSI scores from baseline were evaluated using the pairwise t-test, without adjustments for multiplicity. The impact of patient factors on the PASI 90 response was analyzed using logistic regression models, with odds ratios and 95% confidence intervals calculated.
Statistical significance was determined using the Wald test, and missing data were not imputed. All analyses were performed using SAS version 9.4, following the guidelines outlined in the user’s manual.
Result
A total of 428 psoriasis patients were enrolled, with data from 419 available for the 20-week interim analysis. After excluding patients due to protocol violations and incomplete data, the safety analysis set included 411 patients, while the effectiveness analysis set comprised 245 patients. Demographic data showed a predominance of male patients (65.7%) with an average age of 57.8 years. The majority were treated for plaque psoriasis (PsV), with 37% being elderly patients over 65 years old. The average disease duration was 13.9 years, and over half of the patients had a body surface area (BSA) involvement greater than 10%. Most patients had a history of prior nonbiologic treatments, with apremilast being the most common, and around 46.7% had previously received biologic therapy.
The safety analysis indicated that adverse drug reactions (ADRs) were reported in 6.6% of patients, with 2.2% experiencing serious ADRs. The most common ADRs included infections and skin disorders, with no cases of tuberculosis relapse or hepatitis B virus reactivation reported. A total of 10 patients discontinued treatment due to adverse events, six of which were treatment-related.
Effectiveness analysis showed significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline to week 20, with mean PASI scores dropping from 11.6 to 2.2. Improvements were observed across different patient groups, including those with prior biologic experience and those who switched from nonbiologic treatments. Additionally, quality of life, measured by the Dermatology Life Quality Index (DLQI), improved significantly, with over half of the patients achieving scores indicating no impact of psoriasis on their quality of life by week 20. Nail psoriasis severity also decreased notably by week 20, with a significant reduction in Nail Psoriasis Severity Index (NAPSI) scores. Factors associated with achieving a higher PASI response included lower baseline PASI scores and previous biologic treatment.
Conclusion
This interim post-marketing surveillance (PMS) analysis offers valuable real-world insights into the safety and effectiveness of Guselkumab (GUS) during the first 20 weeks of treatment in Japanese patients with psoriasis. Unlike clinical trials, real-world studies such as this PMS are more inclusive, often involving elderly patients and those with prior treatment experience, who are usually underrepresented in clinical trials. This study observed a higher mean age (57.8 years) compared to the Phase III PSO3004 trial (47.8 years) for GUS in Japan and a greater proportion of patients (46.7%) with prior biologic treatment experience versus the PSO3004 trial (17.5%). The study also noted differences in oral treatment history, particularly with the use of Cyclosporine (CyA) and Apremilast (APR). Only 8.5% of patients in this PMS had previously used CyA compared to 44.4% in the PSO3004 trial, while 23.6% of participants had used APR, reflecting its increasing prescription in Japan since 2017.
The disparities between the PMS and PSO3004 trials, particularly in prior treatment histories, may be attributed to evolving treatment trends and the growing impact of biologics in recent years. This study included more patients with prior treatment experience, which could explain the lower baseline Psoriasis Area and Severity Index (PASI) scores and Body Surface Area (BSA) involvement observed compared to the PSO3004 trial.
The analysis found that 53.5% of patients had at least one comorbidity, such as cardiovascular, metabolic, gastrointestinal, or chronic kidney diseases, consistent with existing literature that links these conditions with psoriasis severity. Psoriatic arthritis (PsA) was another significant comorbidity, affecting 17.8% of patients. The study emphasized the importance of a holistic approach to managing psoriatic disease (PsD), which includes not only treating skin symptoms but also addressing associated comorbidities and making lifestyle adjustments. Early intervention with biologics, such as GUS, may improve prognosis and help prevent new comorbidities, particularly in patients with high disease activity.
Regarding safety, GUS was well-tolerated, with no new safety signals identified. The incidence of adverse drug reactions (ADRs) was comparable to or lower than previously reported rates, further confirming the safety profile of GUS in real-world settings.
Effectiveness outcomes were promising, with significant reductions in PASI scores observed as early as 4 weeks after initiating GUS treatment, and continuing through 12 and 20 weeks. These improvements were consistent across various subgroups, including those with Psoriasis Vulgaris (PsV), PsA, and both with and without prior biologic therapy. Patients who switched to GUS from APR also experienced significant improvements, highlighting GUS’s effectiveness even in those with inadequate responses to APR.
The study explored the combination of biologics with other systemic therapies, specifically examining two CyA patient subgroups: those who maintained CyA at the start of GUS treatment and those who discontinued it before starting GUS. Both subgroups showed notable decreases in PASI scores within 4 weeks, suggesting that discontinuing CyA may not significantly impact treatment efficacy in maintaining disease control.
In patients with PsV, the study evaluated PASI 90, absolute PASI, and Dermatology Life Quality Index (DLQI) responses. The PASI 90 response at 20 weeks was 51.9%, lower than the 77.8% observed in the PSO3004 trial, which may be due to the real-world study’s inclusion of patients with lower baseline PASI scores and prior biologic use. Achieving absolute PASI scores of ≤2 or 3, which indicate clinically meaningful improvements, was increasingly recognized as an important measure of treatment effectiveness. By 20 weeks, 69.0% to 83.7% of patients achieved these scores, with around 90% achieving a DLQI score of ≤5, reflecting significant improvements in health-related quality of life.
While this study provides valuable insights, it is important to acknowledge its limitations, including the lack of a control group, the inclusion of patients with different types of psoriasis, and the limited analysis of specific disease subgroups due to small sample sizes. Additionally, the study was limited to a 20-week evaluation period, and longer-term analyses are needed to fully understand the safety and effectiveness of GUS in Japanese patients with psoriasis.
In conclusion, this 20-week interim analysis found no new safety concerns and reaffirmed the favorable effectiveness profile of GUS in treating psoriasis, including in patients switching from APR or another biologic. However, further long-term data is required to gain a more comprehensive understanding of GUS’s safety and effectiveness in this patient population.
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