Tildrakizumab 100mg/1ml solution for injection pre-filled syringes

Background . The role of interleukin-12 (IL-12), interleukin-23 (IL-23), and interleukin-17 (IL-17) has been recognized in psoriasis pathogenesis, and new drugs targeting this axis have already been developed which may provide a new therapeutic approach for patients with moderate to severe psoriasis. Objective . To compare the direct and indirect evidences of the efficacy and safety of brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tildrakizumab, and risankizumab in the short-term treatment of moderate to severe plaque psoriasis using network meta-analysis (NMA). Methods . A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for the available relevant studies. NMA was conducted by Stata 15.0 software using relative risks (RR) with 95% confidence interval to assess the clinical effectiveness and safety. Ranked the efficacy and safety for each drug accordance with the surface under the cumulative ranking curve (SUCRA). Results . This meta-analysis included 28 studies. All the interventions performed better than placebo in short-term achievement. Based on the result of SUCRA, ixekizumab 80 mg every 2 weeks ranked the highest in short-term achievement of PASI 75 (SUCRA = 93.0%). Brodalumab 210 mg ranked the highest in short-term achievement of PASI 100 (SUCRA = 85.0%). Secukinumab 300 mg ranked the highest in short-term achievement of sPGA 0/1 or IGA 0/1 or PGA 0/1 (SUCRA = 98.1%). In terms of having a risk of adverse events, the rates were higher in brodalumab, secukinumab, ixekizumab, and ustekinumab 45 mg compared with placebo. Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of adverse events during short-term treatment (SUCRA = 4.5%). Guselkumab 50 mg ranked the highest in the risk of serious adverse events during short-term treatment (SUCRA = 25.9%). Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of discontinuations due to adverse events during short-ter treatment (SUCRA = 10.7%). Conclusions . IL-17, IL-12/23, and IL-23 inhibitors had high efficacy in the achievement of PASI 75, PASI 100, and sPGA 0/1 or IGA 0/1 or PGA 0/1 in moderate to severe plaque psoriasis after 12 or 16 weeks of treatment. IL-17 inhibitors showed superior efficacy. However, its clinical safety was poor. Risankizumab appeared to have relatively high efficacy and low risk. The clinical tolerance of other biological agents needs to be further observed.

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Objective: To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. Methods and results: Twenty-four randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82–29.54, p p p p p p p p p p p p p p p p p p p p p p  Conclusion: Ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab were highly efficacious and generally well-tolerated when used as treatments for moderate to severe plaque psoriasis.</p

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Background: Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis. Objectives: To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks. Methods: Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50–75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4-week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all-patients-as-treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). Results: At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100-mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200-mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1·7 per 100 patient-years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs] and exposure-adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low. Conclusions: Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab.</p

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BackgroundPsoriatic arthritis (PsA) is a chronic inflammatory disease that impacts both the skin and joints. Currently, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors have become integral components of PsA treatment regimens. Nevertheless, the comparative effectiveness of these IL-targeted therapies remains a subject of ongoing debate. This study employs a network meta-analysis (NMA) approach to systematically evaluate the therapeutic efficacy and safety profiles of various IL-17, IL-12/23, and IL-23 inhibitors.MethodsWe searched PubMed, Web of Science, and Embase for randomized controlled trials (RCTs) to identify eligible research articles. This NMA was implemented by Stata 14.0 software, with odds ratios (ORs) and 95% confidence intervals (CIs) serving as effect and safety measures to evaluate clinical efficacy and safety profiles. Drugs were ranked based on their efficacy and safety profiles using the surface under the cumulative ranking curve values, enabling a comprehensive comparative assessment of interventional strategies. The CINeMA (Confidence in Network Meta-Analysis) online tool was utilized to evaluate the confidence level of the NMA results.ResultsThis NMA included 22 RCTs and 9,241 patients. All intervention groups demonstrated superior efficacy to the placebo group. Based on efficacy endpoints and subgroup analyses, bimekizumab, secukinumab, and ixekizumab exhibited superior short-term efficacy. Notably, subgroup analyses suggested that tildrakizumab may represent a promising therapeutic option for PsA. Regarding safety and the risk of adverse events, all treatments demonstrated no significant differences compared to placebo, except bimekizumab 160 mg every 4 weeks (Q4W) (OR = 1.37, 95% CI: 1.08-1.74). There were no significant differences in terms of serious adverse events and upper respiratory tract infection. Bimekizumab 160 mg Q4W showed heightened risk of nasopharyngitis (OR = 2.30, 95% CI: 1.26-4.22).ConclusionsThis NMA showed that IL-17, IL-12/23, and IL-23 inhibitors demonstrated remarkable efficacy in attaining ACR20, ACR50, ACR70, and MDA after 12, 16, or 24 weeks of treatment. Among these, IL-17 inhibitors-particularly bimekizumab, secukinumab, and ixekizumab-exhibited notably pronounced therapeutic effects. However, bimekizumab showed a less favorable clinical safety profile compared to other biological agents. In contrast, secukinumab and ixekizumab demonstrated a favorable balance of relatively high efficacy and low risk when considering safety profiles.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251023787, identifier CRD420251023787.

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IntroductionModerate-to-severe plaque psoriasis is a chronic disease impacting quality of life (QoL). This network meta-analysis (NMA) compared efficacy and safety of all biologics approved for the treatment of moderate-to-severe plaque psoriasis to better inform providers on mid-term outcomes, with a focus on the interleukin-23 p19 inhibitor tildrakizumab.MethodsMEDLINE®, Embase, and CENTRAL were searched for randomized clinical trials (RCT) from inception through January 2024. RCTs comparing biologics against placebo or each other reporting Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA) 0/1, or Dermatology Life Quality Index (DLQI) 0/1 responses and safety outcomes (adverse events [AEs] or serious AEs [SAEs]) were sought. Bayesian NMAs were performed at week 28 as the primary time point of interest. Analyses were also performed at weeks 12 and 16. Findings were expressed as risk ratios (RR; efficacy outcomes), risk differences (RD; safety outcomes), and numbers needed to treat (NNT) with 95% credible intervals.ResultsOf 7418 publications screened, 187 describing 124 RCTs of 12 biologics were included in the systematic literature review, and 103 RCTs were included for NMA. All treatments demonstrated improved efficacy and QoL vs. placebo at week 28. Tildrakizumab efficacy at week 28 was comparable to risankizumab and guselkumab, respectively, for PASI 75 (RR 8.74 vs. 8.92 and 8.91), PASI 90 (RR 14.09 vs. 14.81 and 14.77), and PGA 0/1 (RR 9.34 vs. 10.29 and 10.23). No biologics exhibited an increased risk of SAEs vs. placebo; tildrakizumab exhibited no increased risk vs. placebo for AEs.ConclusionsThe investigated biologics demonstrated improved efficacy and QoL relative to placebo at week 28, with no increased risk of SAEs vs. placebo through week 16. At week 28, efficacy of tildrakizumab, risankizumab, and guselkumab was comparable. Limitations include lack of placebo comparators after week 12 or 16, which could affect results.

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BackgroundPyoderma gangrenosum (PG) is a rare disease causing painful skin ulcers, typically starting with tender pustules that quickly develop into painful ulcers. Traditional treatments like glucocorticoids and immunosuppressants often have adverse effects and limited efficacy, making them unsuitable for all patients. Recent evidence shows that biological agents are more effective and safer, leading to increased acceptance. However, selecting the most suitable biological agent from the many available options remains a significant challenge for both physicians and patients.ObjectiveTo systematically review the treatment outcomes of two biologics: TNF (tumour necrosis factors)-α inhibitors and IL (interleukin) inhibitors in pyoderma gangrenosum.MethodsA search of Pubmed was conducted on September 7, 2024. A total of 107 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.ResultsA total of 139 patients were included. Ninety-two were treated with TNF-α inhibitors and 47 with IL inhibitors. The number of included cases and the efficacy are Infliximab (n=52, 88.4%), Adalimumab (n=23, 91.3%), Etanercept (n=13, 84.6%), Certolizumab (n=3, 66.6%), Golimumab (n=1, 100.0%), Anakinra (n=11, 100.0%), Canakinumab (n=7, 100.0%), Secukinumab (n=5, 40.0%), Brodalumab (n=3, 100.0%), Ixekizumab (n=1, 100.0%), Ustekinumab (n=12, 100.0%), Spesolimab (n=3, 100.0%), Guselkumab (n=2, 100.0%), Tildrakizumab (n=2, 100.0%), Risankizuma (n=1, 100.0%). Among them, 46.0% (n=64) achieved complete remission, including 47 (33.8%) who used TNF-α inhibitors and 17 (12.2%) with IL inhibitors. And the total effective rate of IL- inhibitors (93.6%) was higher than that of TNF-α inhibitors (88.0%), but had no statistical significance (p>0.05). However, it takes less time for IL inhibitors to reach partial remission or complete remission. Additionally, in infliximab group, the number of adverse events that occurred was large and varied.ConclusionDifference in effective rate shows no statistical significance between two kinds of agents. However, IL inhibitors demonstrate an advantage with shorter treatment cycles. Additionally, Infliximab has a wider range of side effects and should be used with caution.PROSPERO number: CRD42024608039.

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Background Biologics have significantly improved outcomes for patients with psoriasis. However, with multiple agents targeting different immunological pathways, comparative efficacy data is essential to guide optimal treatment selection. Objective To compare the efficacy of eight biologic therapies in achieving Psoriasis Area Severity Index 75 response in patients with plaque psoriasis. Methods A systematic review and network meta-analysis (NMA) was conducted per PRISMA-NMA guidelines. Open-access randomized controlled trials (RCTs) involving adults with plaque psoriasis treated with adalimumab, ustekinumab, secukinumab, ixekizumab, bimekizumab, guselkumab, risankizumab, or tildrakizumab were included. Psoriasis Area Severity Index 75 at approximately 12 weeks was the primary outcome. A frequentist random-effects model was used Results 29 RCTs (13923 participants) were included. 8 biologics were analyzed. All agents outperformed placebo. 11 of the combinations out of 325 had significant inconsistency. Transitivity assumptions based on randomization and study design were not addressed. Ixekizumab 80mg was the best treatment compared to placebo and all other biologics, while increasing dose of all drugs was not always associated with increasing efficacy except in the cases of Ustekinumab

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Vulvovaginal lichen planus (VVLP) is a chronic inflammatory mucocutaneous disease causing significant morbidity. Despite various available treatments, evidence regarding their effectiveness remains fragmented. To systematically evaluate the efficacy and safety of therapeutic interventions for VVLP with or without concomitant gingival involvement. We searched MEDLINE, Embase, CINAHL, and Scopus databases without date restrictions. We included randomized and non-randomized studies reporting treatment outcomes in adults with VVLP. Two reviewers independently screened studies and extracted data. Risk of bias was assessed. We analyzed 1417 patients across 66 studies. Monotherapy was used in 25.2% (357/1417), dual-component therapy in 12.0% (170/1417), triple-component therapy in 51.2% (726/1417), and complex therapy in 11.6% (164/1417) of cases. Among monotherapies, systemic corticosteroids demonstrated the highest complete resolution (CR) rate at 88.9% (24 of 27 patients), followed by biologics with tildrakizumab achieving 88.0% CR (22 of 25 patients), and JAK inhibitors with tofacitinib showing 75.0% CR (6 of 8 patients), and intravaginal corticosteroid suppositories at 55.7% (54 of 97 patients). Triple-component therapy combining systemic corticosteroids, topical calcineurin inhibitors, and antimetabolites (methotrexate or mycophenolate mofetil) was most commonly used (66.8%, 485/726), with 41.6% achieving CR. Adverse events were generally mild, including burning sensations with topical agents and gastrointestinal symptoms with systemic immunosuppressants. Recurrence rates varied widely: 84% for topical corticosteroids alone, 11.9% for methotrexate, and 3.2% for tildrakizumab. While corticosteroids remain the mainstay of VVLP treatment, newer therapies, including JAK inhibitors (75.0% CR, 6 of 8 patients) and biologics, show promising efficacy. Among biologic monotherapies, tildrakizumab achieved 88.0% CR (22 of 25 patients), while the overall CR rate across all 31 biologic-treated patients was 71.0% (22 of 31 patients). These findings are based on small patient numbers and require validation in larger controlled trials. Triple-combination therapy is frequently employed for resistant cases. High recurrence rates with monotherapy suggest combination approaches may be necessary for the long term.PROSPERO Registration: CRD42025101229.

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BackgroundInterleukin (IL)-23p19 inhibitors are increasingly used in immune-mediated inflammatory diseases (IMIDs), particularly inflammatory bowel disease (IBD). Almost half of patients show inadequate response, partly due to pharmacokinetic (PK) variability. However, a comprehensive overview of their PK parameters is lacking, which limits understanding of population variability. This systematic review assessed the PK of IL-23p19 inhibitors in healthy subjects, IBD and other IMIDs.MethodsA systematic literature search was performed in PubMed/MEDLINE and Embase. Studies were screened by two independent researchers. Quality was assessed using the Cochrane risk of bias tool and the Clinical Pharmacokinetic Study Checklist.ResultsA total of 21 studies were included (risankizumab n = 9, guselkumab n = 6, tildrakizumab n = 3, mirikizumab n = 3), covering healthy subjects, psoriasis, psoriatic arthritis, Crohn's disease (CD), ulcerative colitis (UC) and pustular/erythrodermic psoriasis. Only one study examined a distinct IBD group, specifically, mirikizumab in pediatric UC. For risankizumab, dose-normalized maximum concentrations and area under the concentration‑time curves over a dosing interval, along with central and peripheral volume of distribution and clearance were generally similar across CD and UC. Patients with CD and UC demonstrated increased risankizumab trough levels over consecutive dosing intervals, while an opposite trend was observed for other IMIDs. Covariate analysis revealed that only albumin in UC and body weight in CD were relevant covariates to risankizumab PK.ConclusionLimited PK data and lack of subphenotype-specific data on IBD highlight the need for future studies to better define PK parameters. Also, more research is needed to guide personalized dosing strategies for IL-23p19 inhibitor use in IBD, as well as in other IMIDs.

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