Ustekinumab For Psoriasis Research Articles

Ustekinumab: In Psoriasis and Beyond —A Derm atological Perspective

Background Ustekinumab is an interleukin 12/23 inhibitor, approved by the US-FDA for the management of moderate-to-severe plaque psoriasis and psoriatic arthropathy. Purpose This review aims to describe the dermatological implications and applications of ustekinumab. Methodology PubMed and Google Scholar were searched for scholarly articles related to ustekinumab and its utility in dermatology using the search terms “Ustekinumab” AND “Psoriasis” AND “dermatological diseases”. Studies utilising Ustekinumab in psoriasis and other dermatological indications were analysed and formulated into a systematic review discussing the utility of the drug in psoriasis, as well as other dermatological conditions. Results Ustekinumab is a valuable biologic agent for the management of psoriasis and psoriatic arthropathy, as well as other dermatological disorders like hidradenitis suppurativa, lichen planus, pityriasis rubra pilaris, Behcet’s disease, lupus erythematosus, alopecia areata and pyoderma gangrenosum. Conclusion Ustekinumab’s usage is not limited to psoriasis. Its benefit extends to many more dermatological conditions. It is considered to be the biologic of choice in childhood psoriasis and adult psoriatic patients with concurrent Crohn’s disease. Besides, it has an acceptable safety profile.

Ustekinumab for psoriasis and psoriatic arthritis in adolescents with 22q11.2 deletion syndrome

Ustekinumab for psoriasis and psoriatic arthritis in adolescents with 22q11.2 deletion syndrome

Improving the Accuracy of Biologic Drug Survival Data: The Increasing Prevalence of Off-Label Dosing Must Be Considered when Reporting Drug Effectiveness and Safety

Improving the Accuracy of Biologic Drug Survival Data: The Increasing Prevalence of Off-Label Dosing Must Be Considered when Reporting Drug Effectiveness and Safety

Drug Survival of Adalimumab, Secukinumab, and Ustekinumab in Psoriasis as Determined by Either Dose Escalation or Drug Discontinuation during the First 3 Years of Treatment – a Nationwide Cohort Study

The real-world efficacy of biologics may be insufficiently assessed through common drug survival studies. The objective was thus to examine the real-world performance of biologics in the treatment of psoriasis using the composite endpoint of either discontinuation or off-label dose escalation. Using a prospective nationwide registry (DERMBIO, 2007-2019), we included patients with psoriasis treated with adalimumab, secukinumab, and/or ustekinumab, which have all been used as first-line therapy during the inclusion period. The primary endpoint was a composite of either off-label dose escalation or discontinuation of treatment, whereas the secondary outcomes were dose escalation and discontinuation, respectively. Kaplan-Meier curves were used for the presentation of unadjusted drug survival curves. Cox-regression models were used for risk assessment. In 4,313 treatment series (38.8% women, mean age 46.0 years, and 58.3% bio-naivety), we found that the risk of the composite endpoint was lower for secukinumab when compared with ustekinumab (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.59-0.76), but higher for adalimumab (HR 1.15, 95% CI 1.05-1.26). However, the risk of discontinuation was higher for secukinumab (HR 1.24, 95% CI 1.08-1.42) and adalimumab (HR 2.01, 95% CI 1.82-2.22). For bio-naive patients treated with secukinumab, the risk of discontinuation was comparable to that of ustekinumab (HR 0.95, 95% CI 0.61-1.49).

Steps towards implementation of protocolized dose reduction of adalimumab, etanercept and ustekinumab for psoriasis in daily practice

BackgroundDose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients.ObjectivesTo evaluate the implementation of protocolized biologic DR in daily practice.MethodsA pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review.ResultsThe implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR.ConclusionAdditional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.

P19 A case of pyrexia of unknown origin - wrong way round!

P19 A case of pyrexia of unknown origin - wrong way round!

Genome-Wide Association Study of Ustekinumab Response in Psoriasis.

Heterogeneous genetic and environmental factors contribute to the psoriasis phenotype, resulting in a wide range of patient response to targeted therapies. Here, we investigate genetic factors associated with response to the IL-12/23 inhibitor ustekinumab in psoriasis. To date, only HLA-C*06:02 has been consistently reported to associate with ustekinumab response in psoriasis. Genome-wide association testing was performed on the continuous outcome of percent change in Psoriasis Area Severity Index (PASI) at 12 weeks of ustekinumab therapy relative to baseline. A total of 439 European ancestry individuals with psoriasis were included [mean age, 46.6 years; 277 men (63.1%)]. 310 (70.6%) of the participants comprised the discovery cohort and the remaining 129 (29.4%) individuals comprised the validation cohort. Chromosome 4 variant rs35569429 was significantly associated with ustekinumab response at 12 weeks at a genome-wide significant level in the discovery cohort and replicated in the validation cohort. Of psoriasis subjects with at least one copy of the deletion allele of rs35569429, 44% achieved PASI75 (75% improvement in PASI from baseline) at week 12 of ustekinumab treatment, while for subjects without the deletion allele, 75% achieved PASI75 at week 12. We found that differences in treatment response increased when rs35569429 was considered alongside HLA-C*06:02. Psoriasis patients with the deletion allele of rs35569429 who were HLA-C*06:02 negative had a PASI75 response rate of 35% at week 12, while those without the deletion allele who were HLA-C*06:02 positive had a PASI75 response rate of 82% at week 12. Through GWAS, we identified a novel SNP that is potentially associated with response to ustekinumab in psoriasis.

051 STAT3 nuclear translocation in circulating MAIT cells is a potential biomarker of clinical outcome to ustekinumab in psoriasis

Biologic drugs, such as ustekinumab, have significantly transformed psoriasis treatment. Ustekinumab targets the shared interleukin (IL)-12/23p40 subunit, preventing IL-23 from binding to its receptor and blocking translocation of Signal Transducer and Activator of Transcription 3 (STAT3). Although ustekinumab is highly effective, clinical response is variable and there is an unmet need for the identification of biomarkers predictive of response. Here we monitor IL-23-induced STAT3 activation in peripheral blood mononuclear cells (PBMCs) to identify predictive biomarkers of outcome to ustekinumab.

Comparison of guidelines for the use of Ustekinumab for psoriasis in the United States, Europe, and the United Kingdom: A critical appraisal and comprehensive review.

The aim of this review is to compare and contrast evidence-based clinical practice guidelines from global dermatological organizations for the use of ustekinumab in psoriasis. Clinical practice guidelines from the American Academy of Dermatology, National Psoriasis Foundation, British Association of Dermatologists, and European S3 were reviewed and compared. Practice guidelines from the three dermatological organizations are similar with regards to treatment dosage and initiation but differ in their recommendations for baseline screening and interval laboratory monitoring, treatment in patients undergoing surgery or receiving live vaccines, and treatment contraindications. Ustekinumab is an effective and well-tolerated systemic treatment for patients with psoriasis and should be considered in the line of therapy that dermatologists discuss with their patients. Consideration should be given to evidence-based practice guidelines of global dermatology organizations to effectively guide treatment decisions in patients with psoriasis.

Evaluation of Psoriasis Area and Severity Index as a Proxy for Bio-markers of Systemic Disease under Treatment with Tumour Necrosis Factor-alpha and Interleukin 12/23 Antagonists in Patients with Psoriasis: A Retrospective Cohort Study of 186 Treatment Cycles.

The efficacy of psoriasis treatments is usually evaluated using the Psoriasis Area and Severity Index (PASI). However, there is a lack of systematic statistical assessments of PASI as a proxy for systemic disease in individual patients. Therefore, a retrospective study of 186 treatments with adalimumab, etanercept, and ustekinumab for psoriasis (341 patient-years) was performed. While PASI significantly and independently correlated with biomarkers of systemic inflammation (especially neutrophil-to-lymphocyte ratio, C-reactive protein), the strengths were only weak-to-moderate and varied considerably inter-individually. A decrease in PASI indicated a neutrophil-to-lymphocyte ratio decrease and a C-reactive protein decrease or stable low margin C-reactive protein in ≥ 80%. Sensitivity, specificity, and positive predictive value of PASI 0 and PASI 2.75 (optimal Youden Index) for low cardiovascular risk C-reactive protein were 24%, 92%, 85%, and 62%, 61%, 76%, respectively. Performance was similar using absolute thresholds and PASI 100 or PASI 75, and overall worse for low cardiovascular risk neutrophil-to-lymphocyte ratio and if psoriasis arthritis was present. In conclusion, PASI allows robust low-order estimates of systemic inflammation, but cannot substitute for laboratory biomarkers for more precise assessments.

Randomized Trial Replication Using Observational Data for Comparative Effectiveness of Secukinumab and Ustekinumab in Psoriasis

Treatments for psoriasis may be less effective in everyday practice than in clinical trials. Emulating a target trial using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide treatment effect estimates that are robust and can inform both clinicians and regulatory bodies. To assess the comparative effectiveness of ustekinumab and secukinumab in patients with psoriasis, and to test whether the relative effectiveness estimate of the CLEAR trial, a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis, can be replicated. This comparative effectiveness research study used a target trial emulation approach and was performed between November 2007 and August 2019. Data were obtained from BADBIR, a multicenter longitudinal pharmacovigilance register of patients with moderate to severe psoriasis in the United Kingdom and Republic of Ireland. Participants had chronic plaque psoriasis, were 18 years or older, and had at least 1 record of a Psoriasis Area and Severity Index (PASI) of 12 or higher before their initiation to secukinumab or ustekinumab. Propensity score (PS) 1:1 matched analysis and inverse probability treatment weighted analysis were performed. The primary outcomes were the risk ratio (RR) and the risk difference (RD) for achieving PASI of 2 or lower after 12 months of therapy for secukinumab compared with ustekinumab. Methods to account for missing outcome data were complete case analysis, nonresponder imputation, last observation carried forward, inverse probability of censoring weighting, and multiple imputation. Regulatory and estimate agreement metrics were used to benchmark the effect estimates in this study against those in the CLEAR trial. A total of 1231 patients were included in the analysis, with 917 receiving ustekinumab and 314 receiving secukinumab. Secukinumab was superior to ustekinumab in all analyses, except under the nonresponder imputation method, in the proportion of participants achieving a PASI of 2 or lower (PS-weighted complete case analysis: RR, 1.28 [95% CI, 1.06-1.55]; RD, 11.9% [1.6-22.1]). All analyses, except for nonresponder imputation, reached regulatory agreement in both PS-matching and PS-weighted analyses. This comparative effectiveness study found that secukinumab resulted in more patients achieving a PASI of 2 or lower after 12 months of therapy compared with ustekinumab in patients with psoriasis. Target trial emulation in this study resulted in regulatory and estimate agreement with the CLEAR randomized clinical trial; further such studies may help fill the evidence gap when comparing other systemic therapies for psoriasis.

Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study

Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI]= 3.2-4.2) and in 10.6% (95% CI= 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 μg/ml [95% CI=-1.190 to-0.30] and-0.74 μg/ml [95% CI=-1.09 to-0.47], respectively) and higher absolute PASI (6.6 [95% CI= 3.0-9.9] and 1.9 [95% CI= 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI= 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.

Interaction between Smoking and HLA-C*06:02 on the Response to Ustekinumab in Psoriasis

Interaction between Smoking and HLA-C*06:02 on the Response to Ustekinumab in Psoriasis

Repurposing existing trial data to infer relative efficacy of biologics: guselkumab vs. ustekinumab for psoriasis.

Repurposing existing trial data to infer relative efficacy of biologics: guselkumab vs. ustekinumab for psoriasis.

Ustekinumab in psoriasis: Five-year real life experience from a single tertiary centre.

The efficacy and safety of ustekinumab have been demonstrated in randomized clinical trials; however, there are few real-life data evaluating ustekinumab. This observational, retrospective follow-up study included 33 patients with moderate to severe psoriasis vulgaris. Patients were > 18 years old and received at least 16 weeks of ustekinumab. The efficacy of treatment was evaluated as PASI50, PASI75, and PASI90 response rates at 16, 28, 52, 76, and 100 weeks. Side effects associated with ustekinumab were recorded. Of 33 patients, 24 (72.7%) had received 45 mg ustekinumab and 9 (27.3%) 90 mg ustekinumab. At the 16th week of the treatment, 97% of the patients had PASI50, 57.6% had PASI75, and 33.3% had PASI90 response rates. At 16, 28, 52, 76, and 100 weeks, PASI50, 75, and 90 responses were generally higher in naive to biologics and in the 45 mg group than in nonnaive to biologics and in the 90 mg group but the differences were not statistically significant. In conclusion, ustekinumab is an effective and safe treatment option for patients with moderate to severe psoriasis vulgaris. It seems to be more effective in naive to biologics and patients with normal weight.

Long-term safety profile of adalimumab versus ustekinumab in psoriasis: A real world matching-adjusted indirect comparison (MAIC)

Long-term safety profile of adalimumab versus ustekinumab in psoriasis: A real world matching-adjusted indirect comparison (MAIC)

Treatment persistence rates high with ustekinumab in psoriasis

Treatment persistence rates high with ustekinumab in psoriasis

Cutaneous protothecosis in a patient on ustekinumab for psoriasis

Cutaneous protothecosis in a patient on ustekinumab for psoriasis

Long-term therapy with ustekinumab for psoriasis in a patient with a history of malignant melanoma

Dermatologic TherapyVolume 30, Issue 6 e12522 Therapeutic Hotline: Letters Long-term therapy with ustekinumab for psoriasis in a patient with a history of malignant melanoma Spyridon Gkalpakiotis, Corresponding Author Spyridon Gkalpakiotis spyros@centrum.cz orcid.org/0000-0002-6956-5961 Department of Dermatovenerology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech RepublicCorrespondence Spyridon Gkalpakiotis, MD, PhD, MBA, Department of Dermatovenereology, Third Faculty of medicine, Charles University and Faculty Hospital Kralovske Vinohrady, Srobarova 50, Praha 100 34, Czech Republic. Email: spyros@centrum.czSearch for more papers by this authorPetr Arenberger, Petr Arenberger Department of Dermatovenerology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech RepublicSearch for more papers by this authorMarketa Fridman, Marketa Fridman Department of Dermatovenerology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech RepublicSearch for more papers by this authorMonika Arenbergerova, Monika Arenbergerova Department of Dermatovenerology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech RepublicSearch for more papers by this author Spyridon Gkalpakiotis, Corresponding Author Spyridon Gkalpakiotis spyros@centrum.cz orcid.org/0000-0002-6956-5961 Department of Dermatovenerology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech RepublicCorrespondence Spyridon Gkalpakiotis, MD, PhD, MBA, Department of Dermatovenereology, Third Faculty of medicine, Charles University and Faculty Hospital Kralovske Vinohrady, Srobarova 50, Praha 100 34, Czech Republic. Email: spyros@centrum.czSearch for more papers by this authorPetr Arenberger, Petr Arenberger Department of Dermatovenerology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech RepublicSearch for more papers by this authorMarketa Fridman, Marketa Fridman Department of Dermatovenerology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech RepublicSearch for more papers by this authorMonika Arenbergerova, Monika Arenbergerova Department of Dermatovenerology, Third Faculty of Medicine, Charles University and Faculty Hospital of Kralovske Vinohrady, Prague, Czech RepublicSearch for more papers by this author First published: 21 July 2017 https://doi.org/10.1111/dth.12522Citations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume30, Issue6November/December 2017e12522 RelatedInformation

The 5-year experience of the use of ustekinumab for psoriasis

The 5-year experience of the use of ustekinumab for psoriasis