Tildrakizumab 200mg/2ml solution for injection pre-filled syringes

BACKGROUND: Recently, the literature has expanded with peer-reviewed studies on immunomodulatory agents' efficacy on scalp psoriasis-which, in turn, widened knowledge gaps regarding these agents' relative effectiveness. We determined the relative efficacy of immunomodulatory monotherapies for scalp psoriasis. METHODS: We ran Bayesian network meta-analyses (NMAs) using outcomes related to Psoriasis Scalp Severity Index (PSSI) and scalp-specific Physician's Global Assessment of clear (0) or almost clear (1) (Sc-PGA 0/1). RESULTS: We estimated the relative efficacy of 22 interventions (including placebo), and analyzed 9 outcomes, namely: proportion of participants who attained Sc-PGA 0/1, proportion of participants who achieved 100% improvement in PSSI (PSSI-100), and proportion of participants who achieved 90% improvement in PSSI (PSSI-90) at 8, 12, and 16 weeks. CONCLUSIONS: We are the first to provide comparative evidence on the efficacy of newly investigated agents such as deucravacitinib, tildrakizumab, roflumilast and icotrokinra. In general, the IL-17 inhibitors (bimekizumab, ixekizumab, secukinumab, brodalumab) and IL-23 inhibitors (icotrokinra, guselkumab, tildrakizumab) were effective depending upon the outcome and time-point being considered. At 16 weeks, for PSSI-100, ixekizumab 150 mg at weeks 0, 2, 4, 8, and 12 ranked highest; at 16 weeks, for Sc-PGA 0/1 bimekizumab 320 mg every 4 weeks ranked highest; at 8 weeks, for PSSI-100 ixekizumab 80 mg every 2 weeks ranked highest; at 8 weeks, for Sc-PGA 0/1 secukinumab 300 mg at weeks 1, 2, 3 and then every 4 weeks ranked highest. Small-molecule therapies (apremilast, deucravacitinib, roflumilast) improved scalp psoriasis modestly. Our work would guide the design of future studies and clinical decision-making.

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BACKGROUND: There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. METHODS: In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. RESULTS: At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician's Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs . 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs . 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. CONCLUSION: Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05108766.

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BACKGROUND: Scalp psoriasis is common and difficult to treat. OBJECTIVE: To evaluate efficacy and safety of tildrakizumab for the treatment of scalp psoriasis. METHODS: In this Phase 3b, randomized, double-blind, placebo (PBO)-controlled study (NCT03897088), patients with moderate-to-severe plaque psoriasis affecting the scalp (Investigator Global Assessment modified [IGA mod] 2011 [scalp] ≥3, Psoriasis Scalp Severity Index [PSSI] ≥12, ≥30% scalp surface area affected) received tildrakizumab 100 mg or PBO at W0 and W4. The primary endpoint was IGA mod 2011 (scalp) score of "clear" or "almost clear" with ≥2-point reduction from baseline at W16 (IGA mod 2011 [scalp] response). Key secondary endpoints were PSSI 90 response at W12 and W16 and IGA mod 2011 (scalp) response at W12. Safety was assessed from adverse events. RESULTS: Of patients treated with tildrakizumab (n = 89) vs PBO (n = 82), 49.4% vs 7.3% achieved IGA mod 2011 (scalp) response at W16 (primary endpoint) and 46.1% vs 4.9% at W12; 60.7% vs 4.9% achieved PSSI 90 response at W16 and 48.3% vs 2.4% at W12 (all P < .00001). No serious treatment-related adverse events occurred. LIMITATIONS: Only short-term data are presented. CONCLUSION: Tildrakizumab was efficacious for the treatment of scalp psoriasis with no new safety signals.

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Background: Tildrakizumab, the IL-23 inhibitor, is used to treat plaque psoriasis and psoriatic arthritis. Many studies have reported adverse drug reactions (ADRs) associated with Tildrakizumab. Objective: The aim of this study was to describe ADRs associated with Tildrakizumab monotherapy by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: The signals of Tildrakizumab-associated ADRs were quantified using disproportionality analyses such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms. Results: A total of 10,530,937 reports of ADRs were collected from the FAERS database, of which 1,177 reports were identified with tildrakizumab as the “primary suspect (PS)”. Tildrakizumab-induced ADRs occurred against 27 system organ classes (SOCs). A total of 32 significant disproportionality Preferred Terms (PTs) conformed to the algorithms. Unexpected significant ADRs such as coronavirus infection, herpes simplex, diverticulitis, atrial fibrillation and aortic valve incompetence were also possible. The median time to onset of Tildrakizumab-associated ADRs was 194 days (interquartile range [IQR] 84–329 days), with the majority occurring, within the first 1 and 3 months after initiation of Tildrakizumab. Conclusion: This study identified a potential signal for new ADRs with Tildrakizumab, which might provide important support for clinical monitoring and risk prediction.

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INTRODUCTION: Tildrakizumab is a monoclonal antibody targeting interleukin (IL)-23 approved for the treatment of moderate-to-severe plaque psoriasis across two different dosages (100 mg and 200 mg). The higher dosage is recommended for patients with a body weight ≥ 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We conducted a 52-week multicenter retrospective study to compare the effectiveness and safety of both dosages and assess their impact on specific patient subgroups. METHODS: We enrolled a total of 540 patients with high disease burden or body weight ≥ 90 kg; 177 and 363 were treated with tildrakizumab 200 mg and 100 mg, respectively. The effectiveness was evaluated in terms of PASI 90, PASI 100, and PASI ≤ 2 at weeks 16, 28, and 52. We also performed subanalyses according to the body weight (≥ 90 kg), PASI ≥ 16, prior biologic exposure, involvement of difficult-to-treat areas, and the presence of at least one cardiometabolic comorbidity. RESULTS: After 16 weeks of treatment, a higher proportion of patients in the 200-mg group achieved PASI 90 and PASI 100 compared to those in the 100-mg group (43.5% vs. 34.3% and 36.4% vs. 24.2%, respectively). These results were sustained at 1 year, with PASI 90 and PASI 100 reached by 68.6% and 52.9% of patients in the 200-mg group, respectively, versus 57.3% and 35% in the 100-mg group. All subgroup analyses consistently indicated a trend toward greater effectiveness with tildrakizumab 200 mg, particularly in terms of PASI 90 and PASI 100 achievement at weeks 16 and 52. No differences in the safety profile were observed throughout the study period. CONCLUSION: Our findings confirm the superior effectiveness of tildrakizumab 200 mg over 100 mg in specific subgroups of patients with a comparable safety profile across the study period.

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INTRODUCTION: Palmoplantar psoriasis (PPp) has a profound negative impact on patients' quality of life, and it represents a therapeutic challenge, as palms and soles are difficult to treat area. Although the efficacy profile of tildrakizumab has been well evaluated in the literature, data on its use for PPp are still limited. The objective of the study was to evaluate the efficacy and safety of tildrakizumab on moderate-to-severe plaque psoriasis with involvement of the palmoplantar area. METHODS: A multicenter, retrospective, real-life study was performed enrolling patients with moderate-to-severe plaque psoriasis involving the palmoplantar area undergoing treatment with tildrakizumab with a follow-up of at least 52 weeks. At baseline, demographic and clinical data were assessed. Psoriasis severity was evaluated by using Psoriasis Activity Severity Index (PASI), body surface area (BSA), Psoriasis Global Assessment (PGA), Pruritus-Numerical Rating Scale (P-NRS) and Dermatology Life Quality Index (DLQI). Palmoplantar PASI (ppPASI) was used to evaluate psoriasis severity in the palmoplantar region. Clinical improvement was evaluated at each follow-up visit [week (W) 4, 16, 52]. RESULTS: A total of 99 patients were enrolled. A reduction in PASI, BSA, PGA, P-NRS and DLQI was observed at each time point. Mean ppPASI at baseline was 16.9 ± 13.2, which started to improve at W4 (8.9 ± 9.1) and continued to decrease at W16 (2.1 ± 3.1) and W52 (0.5 ± 1.0). Moreover, a sub-analysis showed that the probability of achieving ppPASI50 at W4 increased in case of nail psoriasis (p < 0.05) and decreased in bio-experienced patients (p < 0.001). Similarly, the probability of achieving ppPASI75 at W4 decreased in the case of prior biologic exposure (p < 0.05). Finally, patients with nail psoriasis showed a higher probability of reaching ppPASI75 at W16 (p < 0.05), whereas patients previously treated with systemic therapies for psoriasis reported a reduced probability of ppPASI75 achievement at this time point (p < 0.05). CONCLUSION: Tildrakizumab was shown to be a fast and effective treatment for patients with PPp, being able to achieve significant results already after only 4 weeks of treatment. Moreover, the identification of potential clinical factors predictive of response may improve the selection of the best treatment in patients with PPp.

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