Brodalumab Research Articles

Comparing Achievement of National Psoriasis Foundation Treatment Targets among Patients with Plaque Psoriasis Treated with Ixekizumab versus Other Biologics in Clinical and Real-World Studies.

The National Psoriasis Foundation (NPF) recommends evaluating patient response to treatment at week12, with a target response of ≤ 1% body surface area (BSA) affected by plaque psoriasis and an acceptable response of BSA ≤ 3% or ≥ 75% improvement. This posthoc analysis compared the achievement of NPF target and acceptable responses for ixekizumab (IXE) versus other biologics. Outcomes were evaluated at week12 for patients with moderate-to-severe plaque psoriasis from fourhead-to-head randomized clinical trials (RCTs; UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) and one real-world prospective observational study (Psoriasis Study of Health Outcomes; PSoHO). RCT patients were treated with IXE or etanercept (ETN; UNCOVER-2/3), guselkumab (GUS; IXORA-R), or ustekinumab (UST; IXORA-S). PSoHO patients were treated with anti-interleukin (IL)-17A biologics (IXE, secukinumab, SEC) and other approved biologics for the treatment of plaque psoriasis. Patients with missing outcomes were imputed as non-responder imputation. For RCT data, statistical comparisons between treatment groups were performed using Fisher's exact test with no multiplicity adjustments. For real-world data, adjusted comparative analyses were performed using frequentist model averaging (FMA) and reported as odds ratio (OR). Across the four head-to-head clinical trials analyzed, significantly higher proportions of patients achieved target and acceptable responses at week12 with IXE versus ETN, GUS, or UST. Likewise, the proportion of PSoHO patients achieving target and acceptable response at week12 was higher with IXE compared with other individual biologics. Adjusted comparative analyses showed that IXE had significantly greater odds of target and acceptable response at week12 versus SEC, GUS, risankizumab (RIS), adalimumab (ADA), UST, and tildrakizumab (TILD) and numerically greater odds of target and acceptable response at week12 versus brodalumab (BROD). Across both clinical studies and real-world settings, more patients treated with IXE achieved NPF target and acceptable responses at week12 compared with those treated with other biologics. UNCOVER-2 (NCT01597245); UNCOVER-3 (NCT01646177); IXORA-R (NCT03573323); IXORA-S (NCT02561806); PSoHO (EUPAS24207).

IL-17 inhibitor-associated inflammatory bowel disease: A study based on literature and database analysis.

Objective: Few real-world studies have shown clear association between interleukin (IL)-17 inhibitors and inflammatory bowel disease (IBD) onset. This study investigated the reporting prevalence and evaluated the clinical features and management of IL-17 inhibitor-related IBD events. Methods: We used the US FDA Adverse Event Reporting System database and retrieved data, from 2015 to 2022, on IL-17 inhibitors to identify gastrointestinal inflammatory events and conduct disproportionality analyses by estimating the reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs). Furthermore, case reports and case series, from 2015 to 30 November 2022, on IBD induced by IL-17 inhibitors were collected for retrospective analysis. Results: A total of 388 cases of primary suspected IL-17 inhibitor-associated gastrointestinal events were reported (268 IBD and 120 colitis), including 348 cases involving secukinumab (SEC), 36 cases involving ixekizumab (IXE), and 4 cases involving brodalumab (BRO). Statistically significant reporting rates of total IBD events were observed for SEC and IXE (ROR = 2.13, 95% CI [1.96-2.30] and ROR = 2.79, 95% CI [2.39-3.27], respectively), whereas BRO did not trigger a safety signal. Twenty-nine studies, which included 34 cases, showed evidence of IBD, following SEC (79.4%) and IXE (20.6%) treatment. The median age was 42years; typical initial symptoms included diarrhea (90.9%), abdominal pain (57.6%), bloody diarrhea (51.5%), and fever (36.4%). The median time to onset of IBD symptoms was 2.9months. Some cases were accompanied by elevated white blood cell (WBC) count (87.5%), erythrocyte sedimentation rate (ESR; 85.7%), C-reactive protein (CRP; 100%), and fecal calprotectin (FC; 100%). Cessation of IL-17 inhibitors plus treatment with corticosteroids and TNF antagonists, as either monotherapy or in combination, could lead to complete clinical remission. The median time to remission after IL-17 inhibitor discontinuation was 4weeks. Conclusion: IL-17 inhibitor treatment is associated with exacerbation and new onset of IBD and colitis. Obtaining a detailed patient history before initiation of treatment and monitoring gastrointestinal symptoms and intestinal inflammatory biomarkers during IL-17 inhibitor treatment is important for safe use of these drugs.

Maintenance and Improvement of Skin Clearance Response With Brodalumab Among Patients With Moderate-to-Severe Psoriasis

Abstract not available.

Long-term Efficacy, Safety, and Patient-Reported Outcomes in a Phase 2 Study of Brodalumab

Abstract not available.

Importance of Complete Skin Clearance on Quality of Life: Analysis of Three Phase 3 Studies of Brodalumab

Abstract not available.

Long-term Efficacy and Safety of Brodalumab in Patients With or Without History of Psoriatic Arthritis: Analysis of Two Phase 3 Psoriasis Studies

Abstract not available.

Long-term Efficacy and Safety of Brodalumab in Patients With Psoriasis Disease Duration <10 and ≥10 Years: Analysis of Two Phase 3 Studies

Abstract not available.

Brodalumab in the treatment of moderate-to-severe psoriasis in patients who have previously failed treatment with anti-interleukin-17A therapies

Brodalumab in the treatment of moderate-to-severe psoriasis in patients who have previously failed treatment with anti-interleukin-17A therapies

PSY103 - MODELLING AVERAGE COST AND COST-PER-RESPONDER FOR BIOLOGICAL TREATMENTS FOR MODERATE-TO-SEVERE PLAQUE PSORIASIS WITH DOSE ESCALATION AND REAL-WORLD DRUG SURVIVAL

The cost of biological treatment of moderate-to-severe plaque psoriasis in real life depends not only on price and dosing schedule, but also on dose escalation and drug survival. A number of real-world studies have shown dose escalation with etanercept (ETA), infliximab (INF) and ustekinumab (UST) as well as high levels of discontinuation with secukinumab (SEC), INF and ETA. The aim of this study was to model the impact of dose escalation and drug survival on average cost and cost-per-responder. Drug survival and cost of treatment was modelled over 5 years in periods of 4 weeks using discontinuation rates estimated from a literature review. Discontinuation rates were assumed to be linear over time. Costs included drug costs based on labelled dosing or pivotal trials at public selling prices in Sweden. Dose escalation was modelled using a dose multiplier from week 13 for ETA and INF and week 25 for UST, reflecting average dose escalation found in real life. Average costs per 4-week treatment were calculated as total costs divided by total number of treatment periods. Costs from year 2 to 5 were discounted using an annual 3% discount rate. Average cost per PASI100 responder was calculated based on response rates at week 12 or 16 from a Network Meta-Analysis. Sensitivity analyses was conducted for dose multipliers and discontinuation rates. The average cost-per-responder varied between 27.000 SEK for brodalumab (BRO) and ixekizumab (IXE) and 94.000 SEK for UST. Costs-per-responder were sensitive to dose multiplier and less sensitive to drug survival. Costs per responder were more predictable for BRO and ADA than other biologics. Dose escalation and shorter drug survival have high impact on average cost and cost-per-responder. Low induction costs result in more predictable average costs and costs-per-responder. More real world evidence is needed for modern biologics.

Maintenance of response to brodalumab at 52 weeks among patients with moderate-to-severe psoriasis: Post hoc analysis of two phase 3 studies

Maintenance of response to brodalumab at 52 weeks among patients with moderate-to-severe psoriasis: Post hoc analysis of two phase 3 studies

Brodalumab good choice in psoriasis

Brodalumab good choice in psoriasis

Improvement of Nail Psoriasis with Brodalumab in Phase 3 Trials

Abstract Not Available

Improvements in Lesional Pain and Itch Symptoms with Brodalumab in Psoriasis Studies

Abstract Not Available

Brodalumab withdrawal

Brodalumab withdrawal

Efficacy and safety of antiinterleukin-17 biological agents in the treatment of psoriasis

Psoriasis is a chronic inflammatory proliferative skin disease induced by aberrant cellular immunity under the interactive effect between polygenic and environmental factors. The exact pathogenesis of psoriasis remains unclear, and interleukin-17 (IL-17)is currently considered to play a critical role in it by stimulating the proliferation and aberrant activation of keratinocytes. Three newly developed biological agents targeting the interleukin-17 pathway have been used to treat psoriasis in clinical trials or practice, including secukinumab and ixekizumab that directly antagonize IL-17A, as well as brodalumab that inhibits downstream signal molecules of the IL-17 signaling pathway by antagonizing IL-17RA. They have proved to be effective and safe in the treatment of psoriasis vulgaris and psoriatic arthritis in clinical trials, and provided new choices for the treatment of psoriasis. However, there is still a need for long-term evaluation of their safety. Key words: Psoriasis; Interleukin-17; Biological agents; Therapeutic uses; Safety

Brodalumab vs. Ustekinumab for Psoriasis

The cytokine IL-17 is central to pathogenesis of psoriatic skin disease. Antibodies to IL-17 or to the IL-17 receptor (brodalumab) are approved or in late-stage clinical trials. Cytokine IL-23 has also been implicated in psoriasis; ustekinumab, an antibody to IL-23, is effective and FDA-approved for psoriasis. These authors conducted two phase III trials comparing brodalumab with ustekinumab and placebo in nearly 3500 patients with moderate-to-severe plaque-type psoriasis. At week 12, approximately 85% of 210-mg brodalumab recipients …

Al-Zn-Si系合金の状態圖に就て

The equilibrium diagram of Al-Zn-Si alloys on the side of Al-Zn was investigated by thermal and dilatometrie analyses From the experimentals result the diagram is ascertained to consist of the primary crystallization surfaces (Al)α, (Al)β, (Zn) and Si, and univariant reaction lines Liq._??_(Al)α+Si Liq._??_(Al)β+Si Lip.+ (Al)α_??_(Al)β and invariant points Liq.+(Al)α_??_(Al)β+Si Liq._??_(Al)β+(Zn)+Si. From this diagram the reason why the Al-Zn diagrams given hitherto was different from one another is explained theoretically.