Revisión sistemática

No clasificado

Formulary review of 2 new biologic agents: Tocilizumab for rheumatoid arthritis and ustekinumab for plaque psoriasis

Año 2010
Autores Schafer JA , Kjesbo NK , Gleason PP
Revista Journal of managed care pharmacy : JMCP
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BACKGROUND:

Two autoimmune biologics were recently approved by the

FDA:

ustekinumab in September 2009 for the treatment of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy and tocilizumab in January 2010 for adult patients with moderate to severe rheumatoid arthritis (RA) who have not responded adequately to 1 or more tumor necrosis factor (TNF) antagonist therapies. Both agents use new mechanisms of action and add to the growing group of autoimmune biologics.

OBJECTIVE:

To critically review the phase 3 trials for ustekinumab and tocilizumab and provide managed care considerations in the context of the 9 other biologic agents on the market in the United States that are used to treat moderate to severe RA or psoriasis.

METHODS:

A MEDLINE review was performed for articles published and available through January 2010 using keywords "ustekinumab" and "tocilizumab" with an emphasis on phase 3 trials. The literature search was limited to articles in English, clinical trials, randomized controlled trials, and research conducted in humans. Search results for ustekinumab included 8 articles of which 4 were excluded for not being psoriasis or psoriatic arthritis trials. Search results for tocilizumab included 16 articles of which 8 were excluded for not being RA trials or using biomarkers as primary endpoints. Additional information was obtained from the FDA website.

RESULTS:

Three phase 3 trials are available for ustekinumab. Ustekinumab demonstrated superior efficacy to placebo in 2 trials for the treatment of psoriasis. In a 12-week trial, ustekinumab 45 milligrams (mg) and 90 mg demonstrated significantly higher rates of 75% improvement in the psoriasis area and severity index (PASI 75) (67.5% and 73.8%, respectively) compared with etanercept (56.8%) in the first phase 3 comparative psoriasis trial between autoimmune biologics (P < 0.05 for both comparisons). In a phase 3 trial of RA patients who had failed prior TNF antagonist therapy, a 20% improvement in signs or symptoms according to the American College of Rheumatology criteria (ACR 20) at week 24 was achieved by significantly more study participants in the tocilizumab 8 mg per kilogram (kg) (50.0%) and 4 mg per kg (30.4%) groups than the placebo group (10.1%, P < 0.001 for both tocilizumab groups compared with placebo). Safety data for ustekinumab are limited to use for less than 2 years, and the prescribing information contains warnings regarding infection and malignancy. Tocilizumab is associated with neutropenia, thrombocytopenia, and elevations in lipids and liver function tests. Tocilizumab has unique adverse events when compared with other autoimmune biologics and requires laboratory testing and careful monitoring.

CONCLUSIONS:

Ustekinumab and tocilizumab are new additions to the treatment of autoinflammatory disease. The majority of safety data for both agents are from trials lasting 3 to 6 months. Published long-term safety data for tocilizumab are limited to less than 143 patients treated longer than 5 years, and safety data for ustekinumab are scant beyond 2 years of use; therefore, clinicians should exercise caution prior to widespread adoption. The comparative efficacy and safety trial of etanercept and ustekinumab brings important clinical information to decision makers. Tocilizumab is indicated after failure or intolerance to a TNF antagonist and has unique safety concerns. Managed care plans will consider the experience and long-term data of these agents along with efficacy data and cost when establishing management programs such as prior authorization or step therapy. Copyright © 2010, Academy of Managed Care Pharmacy. All rights reserved.

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Estudio primario

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Cost-efficacy of adalimumab, etanercept, infliximab and ustekinumab for moderate-to-severe plaque psoriasis.

Año 2012
Revista Journal of the European Academy of Dermatology and Venereology : JEADV
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BACKGROUND:

  Different biological agents are used for the treatment of psoriasis. Previous data have shown adalimumab to be the most efficient drug in terms of cost-efficacy. However, newer data are required to include recent drugs.

OBJECTIVE:

  To estimate the cost-efficacy ratios of biological agents licensed in Spain (adalimumab, etanercept, infliximab and ustekinumab) for the treatment of patients with moderate-to-severe psoriasis.

METHODS:

  An economic evaluation model was developed by building a decision tree for each drug regimen for which scientific evidence was available. The payer perspective (Spanish National Health System) was considered, taking into account only the drug costs. Data on efficacy [proportion of patients with a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75)] reported in the randomized controlled trials were used. When more than one trial for each treatment had been published, a meta-analysis was performed. In case of weight-dependent doses (infliximab), weight of the study subjects was standardized by age and gender of the Spanish population, corrected for the increase in weight in subjects with psoriasis. Uncertainty was assessed by sensitivity analysis.

RESULTS:

  Incremental efficacy ranged from 31.19% (etanercept at a dosage of 25 mg twice a week for 12 weeks) to 78.35% (infliximab at 5 mg/kg for 24 weeks). Efficiency, in terms of incremental cost-efficacy, ranged from 8013€ (adalimumab) to 17 981€ (ustekinumab at a dose of 90 mg) per PASI 75 responder gained.

CONCLUSION:

  In terms of cost-efficacy, the most efficient biological drug was adalimumab. The robustness of this finding was confirmed by sensitivity analysis.

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Estudio primario

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Assessment of Sleep Impairment in Patients With Crohn's Disease: Results From the Ustekinumab Certifi Study

Año 2013
Revista Gastroenterology
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Este artículo no tiene resumen

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Revisión sistemática

No clasificado

Comparison of ustekinumab with other biological agents for the treatment of moderate to severe plaque psoriasis: A bayesian network meta-analysis

Año 2012
Autores Lin VW , Ringold S , Devine EB
Revista Archives of dermatology
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Objective: To compare the efficacy of ustekinumab with that of other biological agents using the Psoriasis Area and Severity Index (PASI) among adult patients with moderate to severe plaque psoriasis. Data Sources: We conducted a systematic search of the period January 31, 1992, to February 1, 2012, using MEDLINE (PubMed), Embase, the Cochrane Library, and clinicaltrials.gov. Study Selection: We included randomized controlled trials of biological agents compared with placebo or other biological agents using the PASI in patients who had moderate to severe plaque psoriasis. Data Extraction: Study data were extracted independently by 2 of us, with disagreement resolved by consensus. Data extracted included the size of the trial, follow-up period, age range of patients, disease duration, body surface area involvement, baseline PASI, PASI response, and previous treatment with biological agents. Data Synthesis: A Bayesian network meta-analysis was performed by fitting 3 regression models: a fixed-effects model, a random-effects model, and a random-effects model with meta-regression coefficients. The random-effects model achieved the best fit for these data. In pairwise comparisons, ustekinumab use was associated with statistically significantly higher odds for achieving a 75% reduction in the PASI compared with adalimumab use (odds ratio [OR], 1.84; 95% credible interval [CrI], 1.01-3.54), alefacept use (OR, 10.38; CrI, 3.44-27.62), and etanercept use (OR, 2.07; 95% CrI, 1.42-3.06) but was associated with lower odds compared with infliximab use (OR, 0.36; 95% CrI, 0.14-0.82). In the therapeutic class comparison, the interleukin-12/23 inhibitor had the highest odds for achieving a 75% reduction in the PASI compared with placebo (OR, 69.48; 95% CrI, 36.89-136.46), followed by tumor necrosis factor inhibitors (OR, 42.22; 95% CrI, 27.94-69.34) and the T-cell inhibitor (OR, 5.63; 95% CrI, 1.35-24.24). Conclusion: For the treatment of moderate to severe plaque psoriasis, ustekinumab may be more efficacious than adalimumab, etanercept, and alefacept but not infliximab. ©2012 American Medical Association. All rights reserved.

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Estudio primario

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Relationship of C-reactive protein with clinical response after therapy with ustekinumab in Crohn's disease

Año 2009
Revista The American journal of gastroenterology
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OBJECTIVES:

Ustekinumab induction therapy was studied in a placebo-controlled trial of patients with Crohn's disease (CD; n=104). In patients receiving ustekinumab, 49% achieved clinical response at week 8 vs. 40% for placebo (P=0.34). In a subgroup of patients previously treated with infliximab (n=49), 59% receiving ustekinumab responded vs. 26% receiving placebo (P=0.02).

METHODS:

C-reactive protein (CRP) concentrations were analyzed from serum collected at baseline and at week 8. Change from baseline CRP concentration after treatment, the relationship between baseline CRP concentration and clinical response, and the relationship between baseline CRP concentration and disease location were investigated.

RESULTS:

Mean changes from baseline CRP at week 8 in the primary group were -0.3 and -3.1 mg/l after treatments with placebo (n=43) and ustekinumab (n=46), respectively (P=0.074). In the infliximab-experienced subgroup, the mean changes were +2.0 (placebo, n=23) and -2.6 mg/l (ustekinumab, n=20) (P=0.004). Patients with baseline CRP ≥10 mg/l tended to have lower placebo and a higher ustekinumab response. In addition, more extensive diseases associated with CD in the colon and ileum were reflected by higher CRP concentrations.

CONCLUSIONS:

The potential benefit of ustekinumab in CD is supported by serum CRP reductions. Evidence suggests that increased systemic inflammation as manifested by higher baseline CRP values leads to larger treatment effects with ustekinumab, especially in infliximab-experienced patients. © 2009 by the American College of Gastroenterology.

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Resumen estructurado de revisiones sistemáticas

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Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: a meta-analysis

Año 2012
Autores Tan JY , Li S , Yang K , Ma B , Chen W , Zha C - Más
Revista Database of Abstracts of Reviews of Effects (DARE)
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CRD SUMMARY:

This review found that ustekinumab was a safe and effective treatment for psoriasis in adult patients. Despite some limitations in the review and in the evidence base, the authors' conclusions are likely to be reliable.

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Resumen estructurado de revisiones sistemáticas

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Ustekinumab (Stelara) for psoriatic arthritis - second line after disease modifying anti-rheumatic drugs (DMARDs)

Año 2010
Revista HTA Database
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RECORD STATUS:

None

CITATION:

National Horizon Scanning Centre. Ustekinumab (Stelara) for psoriatic arthritis - second line after disease modifying anti-rheumatic drugs (DMARDs) Birmingham: National Horizon Scanning Centre (NHSC). Horizon Scanning Technology Briefing. 2010

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Revisión sistemática

No clasificado

Comparison of infliximab and ustekinumab for the treatment of moderate-to-severe psoriasis: an indirect comparison meta-analysis.

Año 2015
Autores Fan T , Bennett HA , Smith NE , Marin M , Sen SS
Revista International urology and nephrology
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OBJECTIVES:

As no direct comparisons have been made between infliximab and ustekinumab, the present study's aim was to estimate these drugs' relative efficacy in the treatment of moderate-to-severe psoriasis.

METHODS:

: Eleven randomized controlled trials of infliximab 5 mg/kg and ustekinumab 45 mg or 90 mg, reporting Psoriasis Area and Severity Index (PASI) 75 and PASI 90 end points, were identified from a systematic literature review. Of these, five were excluded because they had inappropriate intervention (n = 1), inappropriate patient population (n = 3), or a small sample size (n = 1). Ultimately, six studies were included in the networks. Log odds ratio (OR) of achieving PASI 75 or PASI 90 was used as the treatment effect in fixed- and random-effects mixed treatment comparison meta-analysis.

RESULTS:

Based on the results of the random-effects model, when compared to infliximab 5 mg/kg, the OR of ustekinumab 90 mg and ustekinumab 45 mg achieving a PASI 75 following 12 weeks of treatment was 0.57 CrI (0.19, 1.29) and 0.44 (0.15, 0.99), respectively. Similarly, the odds of achieving PASI 90 was 0.77 (0.09, 2.70) for ustekinumab 90 mg and 0.63 (0.07, 2.20) for ustekinumab 45 mg. Infliximab 5 mg/kg had the highest probability of being the most effective of all treatments considered, in attaining a PASI 75 (92%) and PASI 90 response (76%). Ustekinumab 90 mg had the highest probability of being ranked second in attaining a PASI 75 (84%) and PASI 90 response (62%). Results from the random- and fixed-effects models were consistent.

CONCLUSIONS:

A greater proportion of patients with plaque psoriasis are expected to achieve a PASI 75 or PASI 90 response when treated with infliximab 5 mg/kg than with ustekinumab 90 mg or 45 mg.

KEYWORDS:

TNF inhibitor, Interleukin 12/23 inhibitor, biologic therapy, comparative effectiveness, randomized clinical trial, PASI score

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Resumen estructurado de revisiones sistemáticas

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Infliximab versus methotrexate, etanercept, adalimumab, and ustekinumab for plaque psoriasis: a review of the comparative clinical efficacy, safety and cost effectiveness

Año 2012
Autores CADTH
Revista HTA Database
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RECORD STATUS:

This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database.

CITATION:

CADTH. Infliximab versus methotrexate, etanercept, adalimumab, and ustekinumab for plaque psoriasis: a review of the comparative clinical efficacy, safety and cost effectiveness. Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH). 2012

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Estudio primario

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Efficacy and safety of ustekinumab in Chinese patients with moderate to severe plaque-type psoriasis: results from a phase 3 clinical trial (LOTUS).

Año 2013
Revista Journal of drugs in dermatology : JDD
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BACKGROUND:

Available biologic agents for the treatment of psoriasis in China are limited.

OBJECTIVES:

The LOTUS study is a phase 3, double-blind, placebo-controlled study that evaluated the efficacy and safety of ustekinumab in Chinese patients with moderate to severe plaque-type psoriasis.

PATIENTS AND METHODS:

Patients (n=322) were randomized to receive ustekinumab 45 mg or placebo at weeks 0 and 4, with placebo crossover to ustekinumab at week 12; all patients were followed up to week 36. The primary end point was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) at week 12. Other end points at week 12 included the proportion of patients with a Physician's Global Assessment (PGA) score of 0 or 1 and the change in Dermatology Life Quality Index (DLQI) score from baseline.

RESULTS:

At week 12, 82.5% of ustekinumab-treated patients achieved PASI 75 responses compared with 11.1% of placebo-treated patients (P<.001). Clinical responses were maintained through week 28, with maximum responses observed at week 24. Significant improvements in PGA and DLQI were observed at week 12 and were generally maintained through week 28. At week 12, adverse events rates were similar between groups (45 mg: 42.5% vs placebo: 38.5%), and serious adverse events were reported in 0.6% of patients in each group. Through week 36, no cases of active tuberculosis, serious infections, malignancies, or major adverse cardiovascular events were reported.

CONCLUSIONS:

Consistent with results previously reported in global phase 3 studies, ustekinumab was highly effective and generally well tolerated in Chinese patients with moderate to severe psoriasis through 36 weeks.

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