Efficacy Of Guselkumab Research Articles

Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study.

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment.

Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study.

Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]), in post hoc analyses of the phase 3, placebo-controlled, randomized DISCOVER-1 and DISCOVER-2 studies. We now evaluate durability of response in axial-related outcomes through 2 years of DISCOVER-2. DISCOVER-2 biologic-naive adults with active PsA (≥ 5 tender/ ≥ 5 swollen joints, C-reactive protein ≥ 0.6 mg/dl) were randomized to guselkumab 100 mg every 4 weeks (Q4W) or at week0, week4, then Q8W, or placebo → guselkumab Q4W at week 24. Among patients with imaging-confirmed sacroiliitis (investigator-identified), axial symptoms were assessed through 2years utilizing BASDAI, BASDAI Question #2 (spinal pain), modified BASDAI (mBASDAI; excludes Question #3 [peripheral joint pain]), and ASDAS. Mean changes in scores and proportions of patients achieving ≥ 50% improvement in BASDAI (BASDAI 50) and ASDAS responses, including major improvement (decrease ≥ 2.0), were determined through week 100. Treatment failure rules (through week 24) and nonresponder imputation of missing data (post-week 24) were utilized. Mean BASDAI component scores were assessed through week 100 (observed data). Exploratory analyses evaluated efficacy by sex and HLA-B*27 status. Among 246 patients with PsA and imaging-confirmed sacroiliitis, guselkumab-treated patients had greater mean improvements in BASDAI, mBASDAI, spinal pain, and ASDAS scores, lower mean BASDAI component scores, and greater response rates in achieving BASDAI 50 and ASDAS major improvement vs. placebo at week 24. Differences from placebo were observed for guselkumab-treated patients in selected endpoints regardless of sex or HLA-B*27 status. At week 100, mean improvements were ~ 3 points for all BASDAI scores and 1.6-1.7 for ASDAS; 49-54% achieved BASDAI50 and 39% achieved ASDAS major improvement at week 100. Guselkumab treatment provided durable and meaningful improvements in axial symptoms and disease activity in substantial proportions of patients with active PsA and imaging-confirmed sacroiliitis. Clinicaltrials.gov NCT03158285.

Efficacy of Guselkumab in Treating Nails, Scalp, Hands, and Feet in Patients with Psoriasis and Self-reported Psoriatic Arthritis.

The aim of this study was to evaluate guselkumab efficacy on regional psoriasis in a subset of psoriasis patients with a self-reported psoriatic arthritis (PsA) diagnosis. In the phase 3 VOYAGE-1 and -2 studies, at week (W)0, patients with moderate-to-severe psoriasis were randomized to guselkumab 100mg, placebo → guselkumab 100mg at W16 through W44, or adalimumab 80mg then 40mg at W1 through W48 (VOYAGE-1) or W24 (VOYAGE-2). Pooled efficacy outcomes, including scalp-specific Investigator's Global Assessment (ss-IGA), hands and/or feet Physician's Global Assessment (hf-PGA), fingernail PGA (f-PGA), Nail Psoriasis Area and Severity Index (NAPSI), and Dermatology Life Quality Index (DLQI), were compared (nominal p-values) through W24 in patients with self-reported PsA diagnosis. Response rates/percentage improvement from baseline were determined, employing treatment failure rules and non-response/no improvement data imputation. A total of 76, 153, and 106 psoriasis patients with self-reported PsA were randomized to the placebo, guselkumab, or adalimumab groups, respectively; the baseline characteristics of patients in all three arms were comparable. At W16, a greater proportion of guselkumab- versus placebo-treated patients achieved ss-IGA 0/1 (80.6% vs. 22.7%, p < 0.001), hf-PGA 0/1 (68.9% vs. 14.8%, p < 0.001), f-PGA 0/1 (47.6% vs. 17.0%, p < 0.001), and DLQI 0/1 (45.6% vs. 2.7%, p < 0.001) responses; mean percentage NAPSI improvement was also greater with guselkumab (39.5% vs. 6.5%, p < 0.001). At W24, patients receiving guselkumab had higher ss-IGA 0/1 (77.5% vs. 58.5%, p = 0.003) and DLQI 0/1 (47.7% vs. 34.3%, p = 0.024) response rates versus those receiving adalimumab. Response rates/mean percentageimprovements at W48 (VOYAGE-1) were numerically greater with guselkumab than adalimumab (e.g., NAPSI improvement: 75.6% vs. 60.9%). Guselkumab-treated patients with psoriasis and self-reported PsA showed meaningful improvements in nail, scalp, and palmoplantar psoriasis. VOYAGE-1 (ClinicalTrials.gov Identifier: NCT02207231) and VOYAGE-2 (ClinicalTrials.gov Identifier: NCT02207244).

Single-Centre Real-Life Experience of Guselkumab in Patients with Moderate-to-Severe Plaque Psoriasis.

The efficacy of guselkumab has been demonstrated in randomized controlled trials, but real-life data are still missing. This study presents a single-center real-life experience in treating moderate-to-severe plaque psoriasis with guselkumab, underlying the efficacy and safety of this biological agent. Primary efficacy endpoint was the percentage of patients reaching psoriasis area and severity index (PASI) 90 response at week 28. The cohort included 79 patients of mean age 51 &plusmn; 15 years. Mean duration of guselkumab treatment was 16,5 &plusmn; 7.5 months. All 79 patients completed at least 28 weeks of treatment. At week 28, 73 (92%) patients reached PASI 50 or higher, 65 (82%) achieved PASI 75 or higher, 54 (68%) achieved PASI 90 or higher, and 35 (44%) reached PASI 100. Very similar percentages were found at week 44 and at the end of the study period. No significant adverse effects were reported. This study confirms that guselkumab is an effective and safe biologic agent capable of maintaining long-lasting clinical response efficacy in real-world clinical practice, although at slightly lower levels than in clinical trials. J Drugs Dermatol. 2022;21(8):864-866. doi:10.36849/JDD.6962.

Current advances in biological therapy of psoriasis: efficacy of guselkumab in real clinical practice

Psoriasis is an immune-mediated, chronic inflammatory skin disease, which is currently regarded as a systemic process given its association with multiple comorbid conditions. In psoriasis, there is a complex interaction between T cells and keratinocytes. The pathogenesis of psoriasis is not fully understood, but the IL-23/Th17 pathway is known to play the key role in the developmentof the disease. With the advent of genetically engineered biological drugs (GEBD), the treatment of psoriasis has undergone significant changes due to their high efficacy through targeted effects. Guselkumab is the first drug for the treatment of moderate to severe psoriasis to target the p19 subunit of interleukin (IL) 23. The efficacy of guselkumab has been demonstrated in a number of clinical trials. To date, only a few case studies from actual clinical practice have been published in the literature reflecting the use of guselkumab in severe psoriasis, including long-term drug survival and continued efficacy in patients with comorbidities. The article reviews the results of key efficacy studies of guselkumab and presents its own clinical case studies of successful use of the drug. It is noted that guselkumab is able to replicate the results obtained in studies in real clinical prachttps tice. However, the cases presented are also of interest in view of their concomitant metabolic syndrome, obesity, which often makes it difficult to respond to therapy. This group of patients is usually characterised by a particularly torpid course of psoriasis and a certain refractoriness to the ongoing treatment. Thus, guselkumab has an effective and safe profile, in addition it is convenient to use, and the improvement in the quality of life of patients during therapy makes it promising as a first-line GEBD therapy in the treatment of psoriasis.

Prospects for the use of monoclonal antibodies to interleukin 23 Gusеlkumab in psoriatic arthritis: New data

Among the pathophysiological mechanisms of immune-mediated inflammatory diseases (IMIDs), specific attention has been paid to the abnormal activation of Th17 type immune response related to the dysregulated synthesis of cytokines forming the interleukin (IL)-23 and IL-17 axis. IL-23 blockade is an innovative approach to the treatment of psoriasis and psoriatic arthritis (PsA). Much of the interest has focused on guselkumab (GUS) (TREMFYA, Janssen, Johnson &amp; Johnson, USA), a fully human IgG λ monoclonal antibody (mAb) targeting the p19 IL-23 subunit and the first-in-class treatment approved for patients with psoriasis and PsA. In patients with psoriasis, GUS is at least as effective as other biologic therapies for PsA and is superior to ustekinumab, an anti-IL-12/IL-23 mAb, and secukinumab, an anti-IL-17 mAb. Compared with TNF-α inhibitors, GUS therapy is less likely to cause infections and does not increase the risk of the reactivation of latent TB infection. The new GRAPPA guidelines (2021) recommend GUS (and other IL-23 inhibitors) for patients with PsA resistant to conventional disease-modifying antirheumatic drugs (DMARDs), who have peripheral arthritis, enthesitis, dactylitis, psoriatic skin and nail lesions. The paper discusses new data on the efficacy of GUS in patients resistant to TNF-α inhibitors, its benefits in patients with axial PsA, and safety during the COVID-19 pandemic.

Anti‐interleukin‐23 for psoriasis in elderly patients: guselkumab, risankizumab and tildrakizumab in real‐world practice

SummaryBackgroundElderly patients (aged ≥ 65 years) represent an increasing proportion of patients with psoriasis and 15% of these have moderate to severe disease. Biologics are being used frequently in this group of patients even though safety and efficacy data are limited. In addition, owing to anti‐interleukin (IL)‐23 therapies being a relatively recent option, no data have been reported about their use in elderly patients with psoriasis.AimTo evaluate and compare the safety and efficacy of guselkumab, risankizumab and tildrakizumab in real‐world practice in elderly patients.MethodsThis was a single‐centre retrospective study that enrolled patients aged ≥ 65 years with moderate to severe plaque psoriasis, treated with guselkumab, risankizumab or tildrakizumab. The length of the study for each group depended on the drug (44 weeks for risankisumab, 40 weeks for guselkumab and 28 weeks for tildrakizumab, owing to its more recent availability in Italy).ResultsIn total, 34 patients were enrolled (n = 20 on guselkumab; n = 8 on risankizumab; n = 6 on tildrakizumab). At Week 4, 29.4% reached 90% improvement in Psoriasis Area and Severity Index (PASI90) and 8.8% reached 100% improvement in PASI (PASI100); at Week 28, PASI90 and PASI100 was reached by 58.8% and 29.4%, respectively. At the final follow‐up (Week 40 or 44, depending on drug), data were available only for the risankizumab (Week 40) and guselkumab (Week 44) and groups, and showed that 71.4% of patients had reached PASI90 and 53.5% had reached PASI100. Four patients (11.7%) discontinued treatment. No significant differences were found between the three groups. The limitations of the study included its retrospective nature of the study, small sample size, and different numbers of patients and follow‐up duration for the different groups (highest for guselkumab, lowest for tildrakizumab).ConclusionThe three anti‐IL‐23 therapies assessed are promising, safe and effective options in elderly patients, and there was no significant difference between them. However, more data are needed to confirm our results and to understand their role in the management of this group of patients.

How should we define disease and outcomes in axial psoriatic arthritis?

Axial involvement (inflammation of sacroiliac joints or spine, or both) is reported in 25–70% of patients with psoriatic arthritis. In The Lancet Rheumatology, Philip J Mease and colleagues 1 Mease PJ Helliwell PS Gladman DD et al. Efficacy of guselkumab on axial involvement in patients with active psoriatic arthritis and sacroiliitis: a post-hoc analysis of the phase 3 DISCOVER-1 and DISCOVER-2 studies. Lancet Rheumatol. 2021; (published online June 29.)https://doi.org/10.1016/S2665-9913(21)00105-3 Summary Full Text Full Text PDF Scopus (12) Google Scholar report data on the efficacy of guselkumab on axial signs and symptoms of psoriatic arthritis. For this pooled analysis, patients with axial involvement defined by local imaging evidence of sacroiliitis from the phase 3 DISCOVER-1 and DISCOVER‑2 trials were selected. The findings showed a substantial improvement in multiple axial outcomes, including the Bath ankylosing spondylitis disease activity index (BASDAI), modified BASDAI (excluding peripheral joint pain), spinal pain, and Ankylosing Spondylitis Disease Activity Score (ASDAS). Efficacy of guselkumab on axial involvement in patients with active psoriatic arthritis and sacroiliitis: a post-hoc analysis of the phase 3 DISCOVER-1 and DISCOVER-2 studiesPatients with active psoriatic arthritis and imaging-confirmed sacroiliitis who were treated with guselkumab every 4 weeks or every 8 weeks had greater mean improvements in BASDAI and ASDAS (as early as week 8) than did placebo-treated participants, with sustained improvements at week 52. Full-Text PDF

Pharmacokinetic/Pharmacodynamic Analysis of Guselkumab for Treatment ofPalmoplantar Pustulosis: Clinical Implications of Guselkumab Dose, Disease Severity, and Smoking in Japanese Patients.

Guselkumab is a human IgG1λ monoclonal antibody that has been approved for treatment of multiple immunologic diseases including palmoplantar pustulosis in Japan. The efficacy of guselkumab in reducing disease severity as compared with placebo has been demonstrated in phase 2 and 3 clinical studies. In some patients assigned to the placebo treatment, worsening of Palmoplantar Pustulosis Area and Severity Index (PPPASI) score was noted. Most of these patients were smokers, raising a possibility of an association of smoking with the disease progression. To understand the clinical implications of guselkumab dose, baseline disease severity, and smoking on the treatment effect and describe the longitudinal relationship between guselkumab exposure and the PPPASI score, a pharmacokinetic/pharmacodynamic modeling analysis was conducted using the pooled data from 1 phase 2 and 1 phase 3 study. Data from 207 Japanese patients (77% women and 60% smokers) with a median PPPASI score of 24.6 were included in the analysis. The observed treatment efficacy (the PPPASI score reduction) appeared to be similar at the current approved dose (100 mg) and the higher dose (200 mg). A greater PPPASI score reduction (in absolute points) is expected in patients with higher baseline PPPASI score (severe disease). However, the higher baseline did not translate to larger magnitude of the change from baseline (in percentage) in the PPPASI score. Incorporating a linear disease progression effect in the model significantly decreased the Nonlinear Mixed Effects Modeling objective function value (P < .001). Smoking status appeared to be related to disease worsening in some patients, but the covariate did not reach statistical significance in the model.

A Case of the Safety and Efficacy of Guselkumab in Psoriasis with Alcoholic Liver Cirrhosis

A Case of the Safety and Efficacy of Guselkumab in Psoriasis with Alcoholic Liver Cirrhosis

Guselkumab in the treatment of patients with plaque psoriasis of moderate and severe severity: Efficacy and safety of interleukin-23 blockade

Materials and methods . In this paper, we review publications on the significance of interleukin-(IL)-23 in the pathogenesis of plaque psoriasis and analyse the results of the 1st and 2nd phase clinical studies, as well as the 3rd phase comparative studies VOYAGE 1, VOYAGE 2, NAVIGATE and ECLIPSE on the efficacy and safety of Guselkumab — a blocker of the p19 subunit in IL-23. The review was conducted using the scientific literature databases PubMed and RSCI. Results. The high efficiency and safety of Guselkumab in the treatment of patients with plaque psoriasis is demonstrated. The PASI 90 value during Guselkumab treatment reached 73.3 % and 80.2 % at the 24th and 16th week (VOYAGE 1). The therapeutic effect persisted following treatment for 48 weeks. It is shown that Guselkumab therapy is effective in patients having undergone unsuccessful therapy with other genetically engineered biological preparations. The reviewed comparative studies show a higher therapeutic efficacy of Guselkumab compared to TNF- α blockers, IL-12/23 p40 subunit, IL-17. The incidence of adverse events during therapy using Guselkumab and other biological drugs used in comparative studies was low and comparable. Conclusion. The IL-23 subunit p19 blocker Guselkumab is an effective and safe drug for the treatment of patients with plaque psoriasis of moderate and severe severity.

Targeting p19 as a treatment option for psoriasis: an evidence-based review of guselkumab.

Further understanding of psoriasis pathogenesis has led to the development of effective biologic medications. Guselkumab (GUS) is a subcutaneously administered monoclonal antibody that targets the p19 cytokine subunit in IL-23 and IL-39 and is US Food and Drug Administration (FDA) approved for the treatment of moderate-to-severe psoriasis in adult patients. This review evaluates the pharmacology, safety and efficacy of GUS in patients with psoriasis. We performed a literature review by searching online databases including PubMed and Google Scholar. In clinical trials, GUS improved diseases including psoriatic arthritis (PsA) and specific areas of disease (scalp, feet, hands and fingernails). In the Phase III trials VOYAGE 1 and 2, more GUS than adalimumab (ADM) patients experienced a ≥90% reduction in Psoriasis Area and Severity Index (PASI) score (PASI90) (VOYAGE 1: 80.2% vs 53.0%; VOYAGE 2: 75.2% vs 54.8%; P<0.001 for both) and Investigator Global Assessment score of 0 or 1 (VOYAGE 1: 84.2% vs 61.7%; VOAYGE 2: 83.5% vs 64.9%; P<0.001 for both) at Week 24. GUS was also successful in treating patients unresponsive to ADM and ustekinumab in the VOYAGE 2 and NAVIGATE trials, respectively. While long-term data are necessary, GUS appears to have a favorable side effect profile with most common adverse effects including nasopharyngitis and upper respiratory tract infections. GUS is a well-tolerated and effective medication for patients with psoriasis. Continued study of GUS and the p19 subunit will help to determine GUS’s ultimate place in therapy.

Guselkumab for the treatment of moderate-to-severe plaque psoriasis

ABSTRACTIntroduction: Guselkumab is a human monoclonal antibody targeting the p19 subunit of IL-23 that has been approved for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This medication blocks the IL-23/IL-17 axis, which has been implicated in playing a key role in the pathogenesis of psoriasis.Areas covered: This review outlines the pharmacologic properties, safety, and efficacy of guselkumab for the treatment of plaque psoriasis.Expert commentary: Guselkumab is the first IL-23 specific inhibitor to be approved for the treatment of plaque psoriasis. Phase II and III clinical trial results have demonstrated excellent safety and efficacy of guselkumab. IL-23 inhibitors may offer potential benefits over existing therapies for moderate-to-severe plaque psoriasis in terms of safety, frequency of administration, and efficacy. Long-term safety data will be critical in evaluating the role of guselkumab in the treatment of psoriasis.

Developments in the Treatment and Management of Psoriasis

The oral session consisted of a talk on the 2-year efficacy and safety of guselkumab in the treatment of moderate-to-severe psoriasis from the Phase III VOYAGE 1 trial. This was followed by an oral session consisting of presentations regarding the clinical efficacy of tildrakizumab in patients with chronic plaque psoriasis over 2 years of treatment, presented from the two Phase III trials, reSURFACE 1 and 2. In the poster session, data were presented on the association between psoriasis and severity index measures, the distribution of improvement measures in psoriasis, and the efficacy of guselkumab in treatment-experienced patients, as well as its impact on the comorbidities of anxiety and depression.

Efficacy of guselkumab within specific body regions in patients with moderate-to-severe plaque psoriasis: Results from the phase 3 VOYAGE 1 study

Efficacy of guselkumab within specific body regions in patients with moderate-to-severe plaque psoriasis: Results from the phase 3 VOYAGE 1 study

Efficacy of guselkumab in patients with moderate-to-severe plaque psoriasis with involvement of the scalp, nails, hands, and feet: Results from the phase 3 VOYAGE 2 study

Efficacy of guselkumab in patients with moderate-to-severe plaque psoriasis with involvement of the scalp, nails, hands, and feet: Results from the phase 3 VOYAGE 2 study