Ustekinumab For Psoriasis Research Articles

Etanercept, adalimumab, and ustekinumab in psoriasis: analysis of 209 treatment series in Austria.

Widely used in the treatment of psoriasis, biologics have been tested in numerous clinical trials. However, drug efficacies and adverse events (AEs) may differ in 'real-world' patients as they do not undergo as rigorous selection and monitoring. Our objective was to examine drug survival, efficacy, and AEs (quality, time of onset) in 'real-world' psoriasis patients treated with etanercept, adalimumab, and ustekinumab. Retrospective data analysis (Jan 1, 2004 to Jun 30, 2015) of patients treated at a psoriasis clinic in an Austrian hospital. All patients who had received at least one dose of etanercept, adalimumab, or ustekinumab were included in the analysis. We analyzed: demographics, drug survival, Psoriasis Area and Severity Index (PASI), as well as quality and time of onset of AEs. In 209 treatment series, the estimated median drug survival varied among the various treatments: 21 months (SE: 6.9) for etanercept, 61 months (SE: 9.4) for adalimumab, and 65 months (SE 1.4) for ustekinumab. Male gender and pretreatment with a biologic were positive predictors of longer drug survival in adalimumab. We found no significant difference in drug efficacy as determined by PASI. Most AEs occur during the first year of treatment. Adalimumab and ustekinumab are marked by longer drug survival compared to etanercept.

Use of TNF-inhibitors and ustekinumab for psoriasis during pregnancy: A patient series

From 2002 to 2016 a total of seven women with severe refractory psoriasis were exposed to the TNF-inhibitors infliximab and adalimumab or to the IL12/23 inhibitor ustekinumab during one or more pregnancies. Maternal, fetal or teratogenic toxicity were not detected during pregnancy and puerperium. All pregnancies were uneventful and resulted in delivery of 10 healthy children in total, one of the women is due February 2017. Postpartum, five of the women were lactating, but none of the women or newborns developed adverse reactions. Data on safety of treatment during breastfeeding are sparse, but so far appears to be safe due to the lack of absorption across the gastrointestinal lining. Currently biological therapy with either TNF-inhibitors or ustekinumab is not recommended during pregnancy, however in selected women with severe psoriasis these treatment modalities may be considered.

Dosing patterns with and cost impact of etanercept and ustekinumab for psoriasis in a real-world setting

Dosing patterns with and cost impact of etanercept and ustekinumab for psoriasis in a real-world setting

Letter regarding Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis

Letter regarding Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis

BackgroundEarly clinical studies suggested that the anti–interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.MethodsIn two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician’s global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100).ResultsAt week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab.ConclusionsBrodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.)

Development of clinical prediction models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis, based on the BIOBADADERM cohort

Background: Identifying patients likely to have very good or bad results from systemic psoriasis therapy could improve efficiency of therapy. Objective: To develop prognostic models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis. Methods: Multivariable logistic regression of a prospective multicenter cohort of psoriatic patients in clinical practice (6449 person-years of follow-up). We used as possible predictors demographic characteristics, comorbidities, characteristics of the psoriasis (type, PASI, arthritis), history of past therapy at entry in the cohort, and history of response to previous cycles while in the cohort. We defined good response to a treatment cycle as either cycle end due to disease remission or a cycle longer than 2 years that does not end later due to inefficacy in the follow-up period. Bad response to a treatment cycle was defined as a cycle that is finished due to inefficacy, based on the physician judgment, after more than 3 months of treatment. Results: Patients with fewer previous therapies, lower body mass index, older at start of therapy, and with previous history of good responses to therapy are more likely to have positive results of therapy. However, the predictive characteristics of models are poor. Conclusion: Predictive models of clinical response to systemic drugs in psoriasis with the studied variables do not seem to outperform drug selection by a dermatologist.

PMS86 - Frequency of Increased Maintenance Doses of Adalimumab, Etanercept, And Ustekinumab

Psoriasis (PSO) and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases. Therapeutic management may include use of biologic agents such as adalimumab (ADA), etanercept (ETN), and ustekinumab (UST). In clinical practice, patients may receive increased doses during the maintenance phase of treatment, exceeding the dosing recommended in FDA labels. The objective of this study was to assess the proportion of patients treated with ADA or ETN for PsA, and ADA, ETN, or UST for PSO who receive an increased maintenance dose. Continuously enrolled adult patients with ≥2 outpatient diagnoses of PsA or PSO were selected from the Symphony PTD Claims Database if their first biologic prescription date (index date) fell between May 2010 and April 2013. Patients were included if (1) full access was available to all pharmacy claims ≥12 months before and ≥12 months after their index date, and (2) they were treatment-naive to the agent of interest pre-index. Treatment with a different biologic pre-index was not considered a reason for exclusion. Dosing was assessed over 12 months post-index. Increased maintenance doses were defined as doses exceeding the FDA label recommendations of ADA 40 mg biweekly, ETN 50 mg weekly, and UST 45 mg every 12 weeks. In total, 15,400 PsA patients and 40,545 PSO patients met the inclusion criteria. The number (proportion) of patients receiving increased maintenance doses for PsA was1,603 of 8,908 (18%) for ADA and 1,300 of 7,647 (17%) for ETN. The number (proportion) of patients receiving increased maintenance doses for PSO was 3,187 of 21,234 (15%) for ADA; 5,201 of 16,318 (32%) for ETN; and 3,136 of 6,915 (45%) for UST. A large subgroup of patients treated with commonly used biologic agents is maintained on increased maintenance doses.

Survival rate of ustekinumab for psoriasis in real life: A multicenter observational study

Survival rate of ustekinumab for psoriasis in real life: A multicenter observational study

Ustekinumab Improves Psoriasis without Suppressing Tumor Antigen-Specific Cytotoxic T Lymphocytes

Background: Ustekinumab is currently used for the treatment of psoriasis with remarkable efficiency. However, worries about the development of malignancies in ustekinumab-treated patients have not been completely resolved because of the major role of IL-12 and IL-23 in tumor immunity. In the present study, we tried to elucidate the effects of ustekinumab on antigen-specific tumor immunity. Methods: After approval by the institutional ethical committee, a 56-year-old male volunteer with psoriasis was administered with 20 doses of WT1 peptide. WT1-specific cytotoxic T lymphocytes (CTLs) were evaluated by WT1 tetramer assay after mixed lymphocyte peptide culture. Results: WT1 tetramer+ T cells with cytotoxic ability appeared in the blood after peptide administration and the frequency of WT1 tetramer+ T cells increased to more than 15 in 10⁶ CD8+ T cells. Thirty months after stopping WT1 administration, the patient commenced treatment with ustekinumab for psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Psoriasis plaques were almost cleared up and the response to ustekinumab has so far lasted for 30 months. The frequency of WT1 tetramer+ T cells has not changed since the initiation of ustekinumab treatment. The effects of ustekinumab on the antigen-presenting and CTL-inducing abilities of dendritic cells were explored in vitro, revealing limited effects on both immune functions. Conclusions: These in vivo/vitro findings imply that ustekinumab improves psoriasis without suppressing tumor antigen-specific CTLs and support the data of recent clinical trials showing no increased incidence of malignancies with ustekinumab treatment.

'Happy' drug survival of adalimumab, etanercept and ustekinumab in psoriasis in daily practice care: results from the BioCAPTURE network.

Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality-of-life measures to drug survival have been published. (i) To describe 1-year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of 'happy' drug survival, defined as Dermatology Life Quality Index (DLQI)≤5 combined with being 'on drug' at a specific time point. Data were extracted from a prospective registry. Drug survival was analysed using Kaplan-Meier estimates. 'Happy' drug survival was calculated, with data split into 'happy' (DLQI ≤5) vs. 'unhappy' (DLQI >5) at baseline and months 3, 6, 9 and 12. 249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1-year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder-corrected drug survival vs. etanercept [hazard ratio (HR) 3·8, P=0·02] and a trend towards better survival vs. adalimumab (HR 2·3, P=0·1). At baseline, the majority (n=115, 73%) was considered 'unhappy' and a minority 'happy' (n=42, 27%) (ratio 'happy':'unhappy' was 1 : 2.7). The percentage of treatment episodes with 'happy' on-drug patients increased to 79% after 1 year. Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be 'happy' in 79% of episodes and 'unhappy' in 21%. We introduced the new concept of 'happy' drug survival because the proportion of on-drug patients with good quality of life is an important indicator for treatment success.

Efficacy and safety of ustekinumab in psoriasis: Our experience

Efficacy and safety of ustekinumab in psoriasis: Our experience

P368 Rare skin disorders in IBD patients treated with anti-TNFs

Background: Skin disorders are the most common adverse effects associated with biological therapy among patients with IBD. The incidence varies according to the series, from 0.5% to 60%. They include reactions at the injection site, infections, complications mediated by the immune system (psoriasis and lupus-like syndrome) and rare skin cancers. We describe a series of rare dermatological manifestations in our IBD patients treated with anti-TNFs. Methods: We collected the cutaneous manifestations of 93 patients with IBD treated with biologics in our environment and we consider “rare cutaneous disorders” as described with a frequency less than 1% in most published series associated with anti-TNFalpha. Results: 6 of the 93 patients (6.45%) developed “de novo” psoriasis, extension more than 5% of the body surface that forced the withdrawal of the anti-TNF. Only one had the typical palmoplantar location while the rest had plates in limbs, trunk and scalp (4 with Infliximab and 2 with Adalimumab). In 5 patients the lesions disappeared after cessation of treatment and the use of topical corticosteroids. In one case improvement was achieved with ustekinumab. The two patients with Adalimumab also associated universal alopecia. The first was a 21 year old woman with Crohn’s disease (CD) with a history of childhood alopecia areata. She developed alopecia universalis after 6 months of treatment with anti-TNF, being then in combination therapy with azathioprine (AZA). The suspension of the drug did not involve the appearance of hair. The second was a 28 year old woman, also with CD, without co-treatment, after 8 months of therapy, in current treatment with ustekinumab for psoriasis with clearly improvement and progressive appearance of hair. A 20 year old male with ulcerative colitis treated with AZA and infliximab (IFX) developed molluscum contagiosum, with papules on the lower extremities. Complete resolution was achieved with podophyllin for 4 weeks and disruption of immunosuppressive therapy. IFX has later continued without relapse. Conclusions: In our series, we found a frequency of 6.45% of severe psoriasiform reactions as paradoxical effect of antiTNFalpha. We found two cases of alopecia universalis (2.5%) and one of them had previously suffered alopecia areata, which may involve a risk for developing this injury using anti-TNFs. Ustekinumab seems to be an appropriate alternative for these cases.

Pharmacogenetics of psoriasis:HLA-Cw6but notLCE3B/3Cdeletion norTNFAIP3polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab

Our understanding of the genetic basis of predisposition to psoriasis is increasing exponentially due to the progress of genetic studies. However, so far little is known about genetic predisposition in relation to the response to psoriasis treatments. Recent data identified genetic predictors for the clinical outcome of conventional treatments such as methotrexate, acitretin and vitamin D derivatives, but few studies are available on genetic predictors of response to biologics. We hypothesized that genetic variations associated with increased risk of developing psoriasis may also act as predictors for the outcome of biologic therapy. The aim of our study was to analyse the presence of three different psoriasis susceptibility genetic variations (HLA-Cw6; TNFAIP3 rs610604 polymorphism; LCE3B/3C gene deletions) in a cohort of patients affected by moderate to severe psoriasis under ustekinumab treatment. Our primary endpoint was to evaluate the association between Psoriasis Area and Severity Index (PASI) 75 response at week 12 and HLA-Cw6 status. Fifty-one patients were genotyped by standard methods and psoriasis severity (PASI score) was evaluated at day 0 and after 4, 12, 24 and 40 weeks of treatment. We observed increased response to ustekinumab in Cw6-positive (Cw6POS) patients [PASI 75 at week 12: 96·4% in Cw6POS vs. 65·2% in Cw6-negative (Cw6NEG) patients; P = 0·008]. In addition, we show that HLA-Cw6POS patients responded faster to ustekinumab, 89·3% of them reaching PASI 50 at week 4, after a single injection (vs. 60·9% of HLA-Cw6NEG patients). The superior response of HLA-Cw6POS patients was maintained throughout the study period, reaching the highest statistical significance for PASI 75 at week 28 (96·35% Cw6POS vs. 72·7% Cw6NEG; odds ratio 9·8). Analysis of TNFAIP3 rs610604 polymorphism and LCE3B/3C gene deletions did not show any significant association with response to ustekinumab. Our observations underline the role of HLA-Cw6 not only as a psoriasis susceptibility gene, but also as a pharmacogenetic marker of response to ustekinumab in psoriasis.

Tolerability of ustekinumab in psoriasis of moderate to high degree associated to Berger disease

Tolerability of ustekinumab in psoriasis of moderate to high degree associated to Berger disease

Hepatitis B virus reactivation during therapy with ustekinumab for psoriasis in a hepatitis B surface-antigen-negative anti-HBs-positive patient

Hepatitis B virus reactivation during therapy with ustekinumab for psoriasis in a hepatitis B surface-antigen-negative anti-HBs-positive patient

Development of the IL‐12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives – an update

Since the original publication of the article "Development of the IL-12/23 antagonist ustekinumab in psoriasis: Past, present and future perspectives" in March 2011 (see Appendix),(1) there have been several new publications and developments of note. A number of new reports from the ustekinumab psoriasis clinical development program have been published. The analysis of efficacy and safety in the PHOENIX 1 long-term extension demonstrated that continuous stable maintenance dosing of ustekinumab was generally well tolerated and sustained durable efficacy through up to three years of treatment.(2) Pooled safety data from the phase 2 and phase 3 global trials showed that the safety profile of long-term continuous ustekinumab treatment through up to three years(3,4) and four years(5) of follow-up was favorable and comparable to what has been reported previously in the shorter-term ustekinumab psoriasis studies.(6-8) This represents the greatest exposure and longest follow-up of psoriasis patients treated with a biologic published to date. Additional phase 3 trials in Asian populations demonstrated similar high levels of efficacy and favorable safety profiles in Japanese,(9,10) Korean,(11,12) and Taiwanese(11,12) patients as those observed in trials conducted in mostly White populations in North America and Europe.(6-8) These data support the positive benefit:risk profile and consistency of response to ustekinumab over years of usage, and in multiple ethnic groups. Results from up to five years of treatment with ustekinumab in the long-term extensions of the phase 3 trials, and the efficacy, safety, and effect on quality of life in Chinese patients will be available in 2012. In addition to clinical trials of ustekinumab for the treatment of psoriasis, 24-week data from one phase 3 study of ustekinumab for the treatment of psoriatic arthritis has recently been presented(13) and another study is ongoing. A Phase 2b trial in Crohn's disease has also been presented,(14) and three phase 3 studies in Crohn's disease are currently in progress.

Accept adalimumab over ustekinumab for psoriasis?

Accept adalimumab over ustekinumab for psoriasis?

Efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: A phase III, randomized, placebo-controlled trial in Taiwanese and Korean patients (PEARL)

Ustekinumab has been evaluated in Caucasian patients with psoriasis, but no studies have been conducted in Asian patients. To assess the efficacy and safety of ustekinumab in Taiwanese and Korean patients with moderate-to-severe psoriasis. In this 36-week, multicenter, double-blind, placebo-controlled study, 121 patients with moderate-to-severe psoriasis were randomized (1:1) to receive subcutaneous injections of ustekinumab 45mg at weeks 0, 4, 16 or placebo at weeks 0, 4 and ustekinumab 45mg at weeks 12, 16. Efficacy endpoints at week 12 included the proportion of patients achieving at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75; primary endpoint), proportion of patients with Physician's Global Assessment (PGA) of cleared or minimal, and change from baseline in Dermatology Life Quality Index (DLQI). At week 12, the proportion of patients achieving PASI 75 was 67.2% and 5.0% in the ustekinumab 45mg and placebo groups, respectively (p<0.001). PGA of cleared or minimal was achieved by 70.5% (ustekinumab) and 8.3% (placebo; p<0.001), and median DLQI changes were -11.0 and 0.0, respectively (p<0.001). Efficacy was maintained through week 28 in ustekinumab-treated patients. Adverse event (AE) profiles at week 12 were similar between the ustekinumab and placebo groups: 65.6% and 70.0%, respectively, had at least one reported AE. Through week 36, no disproportionate increase in AEs was observed, with the exception of abnormal hepatic function, which was related to concomitant isoniazid treatment for latent tuberculosis. Injection-site reactions were rare and mild. No deaths, malignancies, or cardiovascular events were reported. Treatment with subcutaneous ustekinumab 45mg offers a favorable benefit/risk profile for Taiwanese and Korean patients with moderate-to-severe psoriasis. The efficacy and safety profile is consistent with the global phase III studies of ustekinumab in psoriasis.

Development of the IL‐12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives

The development of ustekinumab as a first-in-class anti-interleukin (IL) 12/23p40 therapeutic agent for psoriasis represents an important example of modern and rational drug design and development. Psoriasis is a chronic, systemic, immune-mediated skin disorder with considerable clinical, psychosocial, and economic burden. Ustekinumab is a human monoclonal antibody (mAb) that binds the p40 subunit common to IL-12 and IL-23, key cytokines in psoriasis pathogenesis. The therapeutic mAb was developed using human gamma-1 immunoglobulin (IgG)-expressing transgenic mice, which created a molecule with endogenous IgG(1) biologic properties and low immunogenicity. Ustekinumab was well tolerated in clinical studies and yielded rapid, significant, and sustained efficacy plus improved quality of life/work performance and reduced depression/anxiety. Its pharmacologic properties afford the most convenient dosing regimen among approved biologics, representing a significant advancement in the treatment of moderate to severe psoriasis. Ustekinumab also holds promise for other immune-mediated disorders with significant unmet need.

Positive treatment effects of ustekinumab in psoriasis: Analysis of lesional and systemic parameters

Ustekinumab, a human anti-interleukin (IL)-12/IL-23p40 monoclonal antibody has demonstrated significant efficacy in patients with moderate-to-severe psoriasis. Skin lesion biopsies, cell surface markers on peripheral blood lymphocytes, and ex vivo T-helper (Th)1/Th2 cytokine responses from peripheral blood mononuclear cells (PBMC) from patients receiving ustekinumab 45 or 90 mg, or placebo were evaluated at baseline and week 12. Inflammatory serum protein levels were measured at baseline, week 2 and week 12. At week 12, median epidermal thickness decreased from 312.1 to 132.7 microm, and median levels of cellular proliferation (Ki67) and T-cell infiltration (CD3) decreased by 84.3% and 70.7%, respectively, in the combined ustekinumab group (all P < or = 0.002). Serum levels of tumor necrosis factor (TNF)-alpha, C-C motif ligand 27 (CCL27) and other inflammatory cytokines remained unchanged. Minimal variation in the percentage of T cells expressing cutaneous lymphocyte antigen (CLA) was observed following ustekinumab treatment, with no significant variation in the percentage of cells expressing CD45RA, CD45RO, CD25, human leukocyte antigen-DR (HLA-DR), and C-X-C motif receptor 3 (CXCR3). No apparent effect on the magnitude of Th1/Th2 responses to external stimuli in PBMC was observed following placebo or ustekinumab treatment. Ustekinumab improves histological psoriasis measures, with minimal impact on the systemic immune system.