Objective: The aim of this study was to evaluate the efficacy of ustekinumab in the treatment of enteropathic arthritis. Materials & methods: A systematic literature search was performed in the Pubmed database of publications between January 2010 and October 2021. Demographic characteristics, comorbidities, inflammatory bowel disease and enteropathic arthritis symptoms, other extraintestinal findings, medical treatments and clinical and laboratory findings for all cases were recorded. Results: A total of 11 patients were included. While clinical and laboratory remission was achieved in terms of inflammatory bowel disease in all patients and enteropathic arthritis in nine patients after ustekinumab treatment, other extraintestinal findings for all patients completely regressed after treatment. Conclusion: Ustekinumab may be an appropriate treatment option for this patient group, considering both pathogenesis and successful treatment responses.

BACKGROUND:

Monoclonal antibodies known as biologic agents specifically targeted against interleukin-12 (IL-12), interleukin-17A (IL-17), and interleukin-23 (IL-23) have been the focus of research for moderate-to-severe chronic plaque psoriasis in recent years.

OBJECTIVES:

To discuss the immune-mediated model of psoriasis and to summarize current knowledge of the clinical efficacy and safety of new biologic agents for moderate-to-severe chronic plaque psoriasis.

METHODS:

The PubMed database was searched for relevant articles on ustekinumab, briakinumab, tildrakizumab (MK-322), guselkumab, secukinumab, ixekizumab, and brodalumab published between January 2005 and July 2013.

RESULTS:

Fifty-five articles were identified. These studies suggest that the biologic agents specifically targeting IL-12, IL-17, and IL-23 are efficacious and safe in the treatment of moderate-to-severe psoriasis in adults.

CONCLUSION:

Current data from clinical trials suggest that biologic agents targeting IL-12, IL-17, and IL-23 are safe and efficacious drugs for use in moderate-to-severe chronic plaque psoriasis. Long-term data still need to be established.

The objective of this report is to perform a systematic review of the beneficial and harmful effects of ustekinumab 45 mg or 90 mg for the treatment of active psoriatic arthritis in adults, alone or in combination with methotrexate. Ustekinumab is a fully human IgG1 kappa monoclonal antibody that binds to the shared p40 subunit of interleukin (IL)-12 and IL-23 and is administered by subcutaneous injection of 45 mg or 90 mg at weeks 0 and 4 and every 12 weeks thereafter. Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that can be associated with psoriasis, a skin disease. This seronegative form of arthritis can cause inflammation of the peripheral and axial joints, enthesitis, dactylitis, psoriatic skin lesions, and symptoms such as fatigue that are linked to systemic inflammation. Several classes of drugs are employed in the treatment of PsA, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs; i.e., methotrexate, sulfasalazine, and leflunomide), immunosuppressives (cyclosporine), and tumour necrosis factor (TNF) alpha inhibitors (i.e., etanercept, infliximab, golimumab, adalimumab, and certolizumab). Methotrexate remains the most frequently used DMARD despite limited evidence (two small controlled trials of inadequate power) that evaluated methotrexate for PsA.

OBJECTIVE:

A head-to-head comparator study has shown that the clinical efficacy of ustekinumab is superior to that of etanercept over a 12-week period in patients with psoriasis. Economic models are often hindered by the lack of trials directly comparing outcomes between relevant alternative therapies. The aim of this analysis was to evaluate the cost-effectiveness of ustekinumab versus etanercept among adults with moderate-to-severe plaque psoriasis based on a Phase 3 head-to-head trial.

METHODS:

The Markov model incorporates trial data from the Active Comparator (CNTO 1275/Enbrel) Psoriasis Trial study (ustekinumab 45 mg at Weeks 0 and 4; etanercept 50 mg biweekly) to follow patient response to initial treatment using the modeling approach developed by the Centre for Reviews and Dissemination, University of York, and often cited by others conducting economic analyses of psoriasis. Beyond the initial trial period, the Canadian model extrapolates results up to 10 years.

RESULTS:

Over the 10-year time horizon of the model, the mean annual costs were $16,807 for ustekinumab (45 mg) and $19,525 for etanercept (50 mg). The incremental difference in costs and utilities remained in favour of ustekinumab across a range of sensitivity analyses.

CONCLUSIONS:

This model highlights the advantage of having head-to-head comparative trial data relevant to the at-risk population. Our model shows that ustekinumab is more cost-effective than etanercept for patients with moderate-to-severe plaque psoriasis.

BACKGROUND:

Both the safety and efficacy of biologic therapy may be affected in the presence of highly prevalent chronic viral hepatitis.

OBJECTIVE:

To evaluate the safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and concomitant chronic viral hepatitis.

METHODS:

This was a retrospective, multicentre study. Twenty-five patients with psoriasis and concurrent hepatitis C virus (HCV) (20 patients) or hepatitis B virus (HBV) (five patients) infection who had received at least one biologic agent (etanercept, 21 treatments; adalimumab, four; ustekinumab, four; infliximab, two) were included. Clinical, imaging and laboratory data were recorded.

RESULTS:

In the case of HCV infection, the majority of the patients did not exhibit increases in their viral load or serum liver tests. Aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase were doubled from the baseline measurement in only one patient treated with etanercept. Two other cases exhibited viral load increases during the follow-up period. In total, 18 of the 26 treatments achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75) score during the follow-up period. Two patients treated with etanercept were diagnosed with hepatocellular carcinoma. In the case of HBV infection, all of the patients were being treated with antiviral therapy, and none presented significant variations in viral load or serum liver enzymes. All patients achieved a PASI 75 during follow-up.

CONCLUSIONS:

Biologic therapy was effective and safe for the majority of our patients with HCV and HBV infection, although there may be a risk of reactivation or aggravation. We describe the first cases to receive ustekinumab. The use of biologics should be limited to those cases in which the risk-benefit ratio is justified.

BACKGROUND:

Anxiety, depression, and impaired health-related quality of life (HRQoL) are common in patients with psoriasis.

OBJECTIVE:

We sought to analyze the effect of ustekinumab on these conditions in patients with moderate-to-severe psoriasis.

METHODS:

Patients with moderate-to-severe psoriasis (n = 1230) were randomized 1:1:1 to receive 45 mg of ustekinumab, 90 mg of ustekinumab, or placebo. The Hospital Anxiety and Depression Scale was used to measure anxiety and depression, and the Dermatology Life Quality Index to measure HRQoL.

RESULTS:

At baseline, 40.3% and 26.7% of patients reported symptoms of anxiety and depression, respectively, and 54.6% reported Dermatology Life Quality Index scores greater than 10, indicating a very high impact of disease on HRQoL. Greater improvements at week 12 in mean Hospital Anxiety and Depression Scale-Anxiety (13.9%), Hospital Anxiety and Depression Scale-Depression (29.3%), and Dermatology Life Quality Index (76.2%) scores were reported in ustekinumab groups compared with placebo (P < .001 each).

LIMITATIONS:

Results for these measures are reported only through 24 weeks.

CONCLUSION:

Patients receiving ustekinumab reported significant improvements in symptoms of anxiety, depression, and HRQoL.

BACKGROUND:

Interleukins 12 and 23 have important roles in the pathophysiology of psoriasis. We assessed ustekinumab, a human monoclonal antibody directed against these cytokines, for the treatment of psoriasis.

METHODS:

In this phase III, parallel, double-blind, placebo-controlled study, 766 patients with moderate-to-severe psoriasis were randomly assigned to receive ustekinumab 45 mg (n=255) or 90 mg (n=256) at weeks 0 and 4 and then every 12 weeks; or placebo (n=255) at weeks 0 and 4, with subsequent crossover to ustekinumab at week 12. Patients who were initially randomised to receive ustekinumab at week 0 who achieved long-term response (at least 75% improvement in psoriasis area and severity index [PASI 75] at weeks 28 and 40) were re-randomised at week 40 to maintenance ustekinumab or withdrawal from treatment until loss of response. Both randomisations were done with a minimisation method via a centralised interactive voice response system. The primary endpoint was the proportion of patients achieving PASI 75 at week 12. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00267969.

FINDINGS:

All randomised patients were included in the efficacy analysis. 171 (67.1%) patients receiving ustekinumab 45 mg, 170 (66.4%) receiving ustekinumab 90 mg, and eight (3.1%) receiving placebo achieved PASI 75 at week 12 (difference in response rate vs placebo 63.9%, 95% CI 57.8-70.1, p<0.0001 for 45 mg and 63.3%, 57.1-69.4, p<0.0001 for 90 mg). At week 40, long-term response had been achieved by 150 patients in the 45 mg group and 172 patients in the 90 mg group. Of these, 162 patients were randomly assigned to maintenance ustekinumab and 160 to withdrawal. PASI 75 response was better maintained to at least 1 year in those receiving maintenance ustekinumab than in those withdrawn from treatment at week 40 (p<0.0001 by log-rank test). During the placebo-controlled phase, adverse events occurred in 278 (54.5%) of the 510 patients receiving ustekinumab and 123 (48.2%) of the 255 receiving placebo. Serious adverse events occurred in six (1.2%) of 510 patients receiving ustekinumab and in two (0.8%) of 255 receiving placebo in this phase. The pattern of adverse events was much the same in the placebo crossover and randomised withdrawal phases as it was in the placebo-controlled phase.

INTERPRETATION:

Ustekinumab seems to be efficacious for the treatment of moderate-to-severe psoriasis; dosing every 12 weeks maintains efficacy for at least a year in most patients.

BACKGROUND:

Ustekinumab, a human monoclonal antibody against interleukins 12 and 23, has shown therapeutic potential for psoriasis. This study assessed the efficacy and safety of ustekinumab in psoriasis patients and assessed dosing intensification in partial responders.

METHODS:

In this multicentre, phase III, double-blind, placebo-controlled study, 1230 patients with moderate-to-severe psoriasis (defined by a psoriasis area and severity index [PASI] score > or =12, and at least 10% total body surface area involvement) were randomly assigned to receive ustekinumab 45 mg (n=409) or 90 mg (n=411) at weeks 0 and 4, then every 12 weeks, or placebo (n=410). Partial responders (ie, patients achieving > or =50% but <75% improvement from baseline in PASI) were re-randomised at week 28 to continue dosing every 12 weeks or escalate to dosing every 8 weeks. Both randomisations were done with a minimisation method via a centralised interactive voice response. The primary endpoint was the proportion of patients achieving at least 75% improvement in PASI (PASI 75) at week 12. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00307437.

FINDINGS:

All randomised patients were included in the efficacy analysis. 273 (66.7%) patients receiving ustekinumab 45 mg, 311 (75.7%) receiving ustekinumab 90 mg, and 15 (3.7%) receiving placebo achieved the primary endpoint (difference in response rate 63.1%, 95% CI 58.2-68.0, p<0.0001 for the 45 mg group vs placebo and 72.0%, 67.5-76.5, p<0.0001 for the 90 mg group vs placebo). More partial responders at week 28 who received ustekinumab 90 mg every 8 weeks achieved PASI 75 at week 52 than did those who continued to receive the same dose every 12 weeks (22 [68.8%] vs 11 [33.3%]; difference in response rate 35.4%, 95% CI 12.7-58.1, p=0.004). There was no such response to changes in dosing intensity in partial responders treated with ustekinumab 45 mg. During the placebo-controlled phase, 217 (53.1%) patients in the 45 mg group, 197 (47.9%) in the 90 mg group, and 204 (49.8%) in the placebo group experienced adverse events; serious adverse events were seen in eight (2.0%) patients in the 45 mg group, five (1.2%) in the 90 mg group, and eight (2.0%) in the placebo group.

INTERPRETATION:

Although treatment with ustekinumab every 12 weeks is effective for most patients with moderate-to-severe psoriasis, intensification of dosing to once every 8 weeks with ustekinumab 90 mg might be necessary to elicit a full response in patients who only partially respond to the initial regimen.

Background: Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate to severe psoriasis. Objective: We sought to evaluate the impact of ustekinumab on infections and malignancies, both theoretical risks of blocking IL-12 and IL-23, in patients exposed up to 3 years. Methods: Rates of infections and malignancies were evaluated in cumulative safety data from 3117 ustekinumab-treated patients across 4 studies. Results: During the placebo-controlled periods, rates of overall infections per 100 patient-years were similar among placebo (121.0), ustekinumab 45-mg (145.7), and ustekinumab 90-mg (132.2) groups, with overlapping confidence intervals, and remained stable through 3 years in ustekinumab groups. Rates of serious infections during the placebo-controlled periods were similar between placebo (1.70) and 90-mg (1.97) groups, yet lower in the 45-mg group (0.49). Rates remained stable (90 mg) or decreased (45 mg) over time, and were comparable with those for the US psoriasis population based on a managed care database. Rates of malignancies during the placebo-controlled periods were comparable among groups (placebo: 1.70; 45 mg: 0.99; 90 mg: 0.98) and remained stable over time in ustekinumab groups. Rates of malignancies, excluding nonmelanoma skin cancer, were comparable with rates expected in the general US population based on the Surveillance, Epidemiology, and End Results database. Limitations: Controlled periods do not extend beyond 12 to 20 weeks. Only 1247 patients were treated for at least 2 years, to date. Comparator database populations may not fully represent the clinical trial population. Conclusions: The emerging safety profile of ustekinumab remains favorable and does not suggest increased rates of infection or malignancy through 3 years. © 2011 by the American Academy of Dermatology, Inc.

Background Persistence can predict treatment success and is affected by different factors,such as efficacy, safety, cost and other factors related to the patient. Purpose The objective of this study was to assess persistence of treatment with ustekinumab in patients in a tertiary university hospital, and the causes of discontinuation. Material and methods Retrospective observational study of patients treated at our centre with ustekinumab from January 2009 to September 2015. The persistence of treatment was defined as the time (days) from the date of the first dispensation to one of the following cases: treatment interruption, change or deadline for data entry (30 September 2015). Data were collected from dispensing records to outpatients and review of their medical records. Results 49 patients (22 women and 27 men) were reviewed. The diagnosis was psoriasis (PS) in 71.4% of cases, Crohn's disease/ ulcerative colitis (CD/UC) in 24.5% and psoriatic arthritis (PA) in 4.1%. 32 patients had been treated with anti-TNF (infliximab, adalimumab, etanercept) and all had undergone prior treatment with immunosuppressants. The average treatment duration of patients that were undergoing active treatment as of 30 September 2015 was 942.3 days (PS=977.2, CD/UC=868.8, PA=370). The average number of units dispensed to these patients was 16.4. 26.5% of patients discontinued treatment: 46.2% of them had been diagnosed with CD/UC, 46.2% with PS and 7.7% with PA. The average treatment duration was 364.23 days (PS=325.8, CD/UC=460.8, PA=28). The average numer of units dispensed to these patients was 11.1. 16.7% of patients with PS discontinued treatment after 325.83 days, 50% of patients with CD/UC after 460.8 days and 50% of patients with PA after 28 days. 13 patients discontinued treatment for the following reasons: inefficiency (6), tolerance or adverse effects related problems (2): 1 case of generalised CMV infection and 1 case of recurrent flu-like syndrome and loss of strength in a limb; exitus (2): 1 because of advanced age and 1 because of colon cancer; 1 had moved to another city (1), 1 for personal reasons (1) and 1 for unknown reasons (1). Conclusion 26.5% of patients discontinued treatment with ustekinumab after a period of less than 1 year. The treatment persistence of PS with ustekinumab appears to be greater than the treatment persistence of CD/UC persistence. The results obtained for PA patients cannot be considered representative as there were only two patients. The main cause of non-persistence is treatment failure, followed by tolerance or side effects related problems. These data do not match the literature, and a longer tracking will be necessary to clarify whether this drug has higher or lower persistence than other biological alternatives.