QUASAR Induction Study 1 Cumulative Response to Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis

Introduction: Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission atWeek (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1. Method(s): Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore >=2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IV->GUS 200mg IV;GUS 200mg IV->GUS 200mg SC;GUS 400mg IV->GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure). Matching IV or SC PBO was administered to maintain the blind. Result(s): Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. AtWk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6 % (29/105) of patients randomized to PBO IV (both p< 0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV->200mg SC group and 50.0% (19/38) in the GUS 400mg IV->200mg SC group achieved clinical response at Wk 24. Clinical response atWk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV->GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar toWk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results. Conclusion(s): Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified. (Figure Presented).

Long-Term Efficacy, Safety, and Drug Survival of Guselkumab in Patients with Psoriasis: Real-World Data from the Czech Republic BIOREP Registry.

BACKGROUND: Real-world data on the long-term use of guselkumab for treatment of psoriasis are still limited. OBJECTIVE: We aimed to evaluate long-term efficacy, safety, and drug survival of guselkumab in a real-world setting. METHODS: This is a retrospective study analyzing Czech Republic registry (BIOREP) data of patients treated with guselkumab. RESULTS: In total, 333 patients were included. Improvement in Psoriasis Area and Severity Index (PASI) score was significant. Mean PASI score decreased from 16 at baseline to 0.7, 0.9, and 0.8 after 12, 24, and 36 months, respectively. Absolute PASI scores of ≤ 3 and ≤ 1 were achieved in 93.9% and 77.9%, 94.2% and 71.0%, and 94.8% and 70.7% of patients after 12, 24, and 36 months, respectively. Response PASI 90 and PASI 100 were attained in 81.8% and 57.1%, 75.4% and 50.7%, and 75.9% and 55.2% of patients after 12, 24, and 36 months, respectively. The percentage of patients achieving PASI 90 and PASI 100 responses was higher throughout the study in bio-naive and in normal-weight patients, while presence of psoriatic arthritis had no influence. Improvement in Dermatology Life Quality Index (DLQI) score was also significant; mean DLQI score decreased from 14.2 at baseline to 0.9, 1.0, and 0.7 after 12, 24, and 36 months, respectively. Patients with PASI 100 had lower mean DLQI throughout the study compared with patients with PASI 90. Major reason for discontinuation was loss of effectiveness in 7.1% of patients, while only 0.6% were due to adverse events. Overall cumulative drug survival was high, with only a minimal decline over time, reaching 91.6%, 87.0%, and 85.5% after 12, 24, and 36 months, respectively. Drug survival was not affected by previous biological treatment, patient weight, or presence of psoriatic arthritis. CONCLUSIONS: This real-world study demonstrated the long-term effectiveness, good safety profile, and high drug survival of guselkumab treatment over a period of 36 months.

QUASAR Induction Study 1 Cumulative Response to Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis

Background: Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission at Week (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1. Method(s): Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore >=2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IVGUS 200mg IV;GUS 200mg IV->GUS 200mg SC;GUS 400mg IV->GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure 1). Matching IV or SC PBO was administered to maintain the blind. Result(s): Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. At Wk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6% (29/105) of patients randomized to PBO IV (both p<0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV->200mg SC group and 50.0% (19/38) in the GUS 400mg IV->200mg SC group achieved clinical response at Wk 24. Clinical response at Wk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV->GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar to Wk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results. Conclusion(s): Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified.

Psoriasis flares after COVID-19 vaccination: adherence to biologic therapy reduces psoriasis exacerbations: a case-control study.

This study aimed to evaluate if patients under biologics have a lower risk of psoriasis flares after coronavirus disease 2019 (COVID-19) vaccination than other psoriatic patients. Of 322 recently vaccinated patients admitted for psoriasis at the Dermatological Psoriasis Unit during January and February 2022, 316 (98%) had no psoriasis flares after COVID-19 vaccination (79% under biologic treatment, 21% not biologically treated) and 6 (2%) presented psoriasis flares after COVID-19 vaccination (33.3% under biologic treatment, 66.6% not biologically treated). Overall, psoriasis patients under biologic treatment, developed fewer psoriasis flares after COVID-19 vaccination (33.3%), than patients not under biologic treatment (66.6%) (p=0.0207; Fisher's exact test).

Comparison Of The Efficacy And Safety Of Secukinumab, Ustekinumab And Guselkumab For The Treatment Of Moderate To Severe Plaque Psoriasis: A Systematic Review

Psoriasis is a chronic inflammatory skin condition characterized by scaly erythematous patches or plaques affecting the extensor surfaces that are prominent but spreading to all areas of the body, including the flexor surfaces. Psoriasis occurs when the body's immune system attacks the skin;the interleukin (IL)-12 and IL-17/23 axes play a major role in its pathogenesis. Biologic therapies targeting IL-17 or IL-23 have emerged as an important treatment option for psoriasis and have led to substantial improvements in patients' quality of life. This systematic review aimed to evaluate the comparative efficacy and safety of secukinumab, ustekinumab and guselkumab for the treatment of moderate to severe plaque psoriasis. Based on the final analysis, there were 10 articles, namely 5 RCTs and 5 observational. We found that patients who were given secukinumab showed a rapid response, whereas guselkumab was superior in terms of long-term response (approximately 1 year) and complete remission compared to other biologics. Among all the biologics assessed, ustekinumab showed relatively low efficacy.

Adalimumab, Ustekinumab, and Secukinumab in the Management of Hidradenitis Suppurativa: A Review of the Real-Life Experience.

To date, adalimumab (ADA) is the only biotechnology drug approved for the management of hidradenitis suppurativa (HS), an inflammatory skin condition. However, it quickly became apparent that the efficacy of adalimumab in daily practice was highly variable. In our review, we highlighted the current evidence from literature on the use of biologics in HS in a real-life setting, particularly adalimumab, secukinumab and ustekinumab. Data on the effectiveness and safety of biologic drugs in HS management have been analyzed. Even if the results are promising, more studies are needed. In our opinion, the armamentarium of drugs for HS management is increasing, and treatment will be based on a tailored-tail approach, minimizing the risk of adverse events. In this context, we want to point out the reported effectiveness and safety data concerning adalimumab, ustekinumab and secukinumab as well as ixekizumab.

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 & 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.

A case of cutaneous vasculitis following third dose of SARS-CoV-2 vaccine in an immunocompromised patient

A 58-year-old man known to dermatology services, established on guselkumab for psoriasis and methotrexate for psoriatic arthritis, attended with an acute onset purpuric rash distributed over both his lower limbs, one day after his third dose of SARS-CoV-2 Pfizer-BioNTech vaccine (booster). He had received his initial vaccinations 6 months prior with no reported reactions. He denied any previous SARS-CoV-2 infection or recent symptoms suggestive of COVID-19. There had been no new recent medications and no systemic symptoms were reported. Examination revealed a nonblanching, palpable, purpuric rash distributed over both lower limbs, clinically in keeping with cutaneous vasculitis. Baseline observations were satisfactory including blood pressure and temperature. Bedside investigations included a urinalysis which revealed no proteinuria or haematuria. Punch biopsies were taken and were consistent with a leucocytoclastic vasculitis (LCV). He was managed symptomatically with potent topical steroids with good clinical response. LCV is classified as a cutaneous, small vessel vasculitis, exclusively characterized by deposition of immune complexes in the dermal capillaries and venules (Baigrie D, Bansal P, Goyal A, Crane JS. Leukocytoclastic vasculitis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing, 2021). LCV following both first and second SARS-CoV-2 vaccinations has been documented in recent literature with a few reports following a third booster dose, and in particular within an immunocompromised population. This particular case has raised questions regarding delayed immune response following SARS-CoV-2 vaccine in this subgroup. The pathophysiology of SARS-CoV-2 vaccine-induced LCV has not been extensively researched;however, it is felt to be caused by offtarget immune activation after the vaccination (Dicks AB, Gray BH. Images in vascular medicine: leukocytoclastic vasculitis after COVID-19 vaccine booster. Vasc Med 2022;27: 100-1).

A real-life experience as a proof of Guselkumab effectiveness and safety in patients with moderate to severe psoriasis.

Psoriasis is a skin disorder characterized by chronic inflammation driven by different immunologic pathways, among which the IL-23/Th17 axis plays a pivotal role. For this reason, the use of IL23p19 inhibitors in psoriasis treatment has been evaluated over the years. Guselkumab, a totally human IgG1 lambda monoclonal antibody, that selectively blocks the p 19 subunit of IL- 23 has demonstrated high efficacy and safety throughout several, randomized, double-blind phase III trials (VOYAGE 1 and 2, NAVIGATE and ECLIPSE). We designed a single-center retrospective cohort study in a population consisting of 46 patients followed from December 2018 to April 2021. After a diagnosis of moderate to severe psoriasis, all the patients were considered suitable to receive treatment with Guselkumab. In our population, among those who achieved clinical improvement in terms of Psoriasis Area Severity Index (PASI), PASI 75, 90, and 100 were achieved on average on weeks 14, 19, 21 respectively. We then analyzed a subgroup of our population, consisting of 35 patients, who had an identical follow-up time of 28 weeks, thus observing the trend in mean PASI at subsequent assessments and the number of patients who had reached PASI 75, PASI 90, and PASI 100 at week 4 (10; 3; 1), week 12 (12; 13; 11), week 20 (7; 6; 2), and week 28 (1; 4; 6), respectively. The results obtained are in line with those obtained from previous studies, thus confirming that Guselkumab is an excellent choice in terms of security, long-term efficacy, and overall tolerance.

American College of Rheumatology/Association of Rheumatology Professionals (ACR/ARP) 2021 Annual Meeting (November 5-9, 2021 - Virtual Meeting).

ACR Convergence is the annual meeting of the American College of Rheumatology (ACR). This year, ACR Convergence was to be held in San Francisco, California, but due to the COVID-19 crisis and subsequent travel restrictions, it was changed to a virtual meeting format. The meeting comprised several days of live sessions and on-demand virtual content including posters and prerecorded presentations.

Successful guselkumab treatment in a psoriatic patient affected with Cornelia de Lange syndrome, and prosecution during the COVID-19 pandemic.

Psychomotor delay and intellectual disability are potential limitations in psoriasis management, due to low compliance, and strict dependence from caregivers intervention. We report our successful experience with a 58-year-old woman, who was genetically affected by Cornelia De Lange syndrome, which causes intellectual disability and psychomotor disorders. The patient had been already treated with topical and traditional therapies, without any clinical benefits. Eventually, she adhered to guselkumab treatment. The compliance was excellent, significant improvements were observed after only 3 months of treatment, without adverse effects. During follow-up, the COVID-19 pandemic address concern on the possible increased risk of infection due to immunosuppression. In agreement with current Italian recommendations, risk and benefits profile was discussed with the patient's legal tutor and the decision to continue the treatment was taken. Psoriasis complete clarification was maintained during the most difficult period of the Italian outbreak, allowing the patient to remain safely at home.