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New Data Demonstrate Stelra® (Ustekinumab) Is Effective, Well-Tolerated And Improved QOL In Patients With Moderate To Severe Plaque Psoriasis

A series of data presentations released at the 21st European Academy of Dermatology and Venereology (EADV) congress, in Prague, Czech Republic, demonstrate that STELARA® (ustekinumab) is effective, well tolerated and improved quality of life in patients with moderate to severe plaque psoriasis.

Specifically, efficacy results from the 52-week TRANSIT study showed that ustekinumab is highly effective and well-tolerated in patients inadequately responsive to methotrexate,1 and that ustekinumab substantially improved quality of life outcomes in patients transitioned from methotrexate regardless of transition strategy.2 Additionally, results from the PHOENIX 2 study demonstrated that high levels of clinical responses were achieved and maintained through up to five years of ustekinumab treatment.3

In terms of safety, an integrated analysis of safety data from four randomised-controlled studies representing approximately 9,000 patient-years (PY) of follow-up showed that in general, there was no dose-response or cumulative effect of increasing duration of exposure to ustekinumab on the rates of overall and targeted adverse events after up to five years of treatment.4 In addition, data from the PSOLAR Registry’s annual database extract (last conducted in August 2011, representing a total of 13,733 PY) described malignancy (excluding non-melanoma skin cancers), infection and major adverse cardiovascular event (MACE) rates in patients eligible for systemic therapies, including ustekinumab and infliximab.5 No new safety signals for ustekinumab and infliximab were detected in this analysis.6,7

Ustekinumab targets interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in regulating immune responses and are thought to be associated with immune-mediated inflammatory diseases such as plaque psoriasis.

Professor Jörg Prinz, University of Munich, Germany, said “The findings from these studies are promising and support a favourable benefit-to-risk profile for ustekinumab with up to five years of treatment. Importantly results demonstrated in clinical trials are consistent with the real-world experience to date. These findings further advance our understanding of biologics, not just in terms of efficacy, safety and tolerability, but also health-related quality of life.”

Psoriasis is a chronic, immune-mediated inflammatory disease, which is highly visible on the patient but incurable. It is often very painful and associated with multiple physical and psychological burdens such as depression.8 There is now a recognised need for improved standards of care for each and every person living with psoriasis in Europe today, and to address this need the European Expert Working Group for Healthcare in Psoriasis recently launched a Europe-wide framework9 (White Paper) to improve standards of care for patients, especially in terms of access to the right targeted treatment appropriate for their disease severity.

Source

Study Design and Results

TRANSIT study
Design: A 52 week, open-label, Phase 4 study of 489 patients designed to compare two methods oftransitioning patients from methotrexate to ustekinumab. The first was discontinuation of methotrexatewith immediate initiation of ustekinumab and the second was initiation of ustekinumab with overlap andgradual dose reduction of methotrexate over four weeks. Results: Ustekinumab was well tolerated, with 8% of patients in each transition arm experiencing aserious adverse event (AE), and associated with sustained efficacy; 76% and 77% of patients, in themethotrexate immediate cessation arm and the methotrexate gradual withdrawal arm respectively,achieved at least a 75% improvement from baseline in their Psoriasis Area and Severity Index score (PASI75) at Week 52. The data showed there was no difference in terms of the number and types of AE orefficacy outcomes, whether given ustekinumab after immediate cessation of methotrexate or ifmethotrexate is gradually withdrawn over 4 weeks.1

PHOENIX 2
Design: 1,230 patients with moderate-to-severe plaque psoriasis were randomised to receive ustekinumab45 mg or 90 mg at weeks 0, 4 and every 12 weeks thereafter, or placebo at weeks 0 and 4. Patientsinitially randomised to placebo at baseline were assigned to cross over to either ustekinumab 45 mg or 90mg at weeks 12, 16 and every 12 weeks thereafter. Investigators were permitted to adjust ustekinumabdosing based on clinical judgment after Week 52 of the study.* Results: With up to five years of ustekinumab treatment, high levels of clinical responses were achievedand maintained in the overall population; 76.5% and 78.6% of patients who received STELARA 45 mg and90 mg, respectively, achieved a PASI 75 response at the end of the treatment period. The safety profile ofustekinumab was generally comparable between patients who received 45 mg or 90 mg, with or withoutdose adjustments.3

*PHOENIX 2 study design involved a revised dosing schedule for partial responders which is not included inthe approved EMA Summary of Product Characteristics for STELARA®.

Clinical Trial Safety Database Analysis

Design: Safety data were pooled from four ustekinumab psoriasis studies (one Phase 2 and three Phase 3[PHOENIX 1, PHOENIX 2, and ACCEPT]) in which patients were treated for up to five years. Rates ofoverall and targeted adverse events were analysed by ustekinumab dose received (45 mg or 90 mg) andby year of follow-up (Year 1 to 5) to evaluate potential dose-response or impact of increasing duration ofexposure.
Results: Analyses included 3,117 patients with a total of 8.998 PY of follow-up. Rates of safety eventswere generally comparable between patients who received 45 mg and 90 mg; and generally consistentover time from Year 1 through 5. The overall safety profile of ustekinumab remained stable in adults withmoderate-to-severe plaque psoriasis receiving up to five years of ustekinumab treatment. No effect ofdose and no effect of increasing duration of exposure were observed.4

PSOLAR
Design: A disease-based registry study that captures multiple forms of psoriasis therapy that is planned toenroll approximately 12,000 patients. In August 2011, 9,495 patients were available in the last annualdata extract reflecting 13,733 PY of exposure. Patients that are eligible for systemic therapies, includingustekinumab and infliximab, are enrolled and followed biannually.
Results: Preliminary findings on rates of infection, malignancy (excluding non-melanoma skin cancers) andmajor adverse cardiovascular events (MACE) observed since the registry opened in 2007 were reported.5-7 In patients exposed to ustekinumab and infliximab, no new safety signals for malignancy, MACE or infection were identified in patients undergoing actual clinical use in more than 250 centresinternationally.5-7

About Psoriasis

Psoriasis is a chronic disease caused when the immune system mistakenly attacks healthy skin cells,speeding up skin cell production.10 Plaque psoriasis, the most common type of psoriasis,11 often results inpatches of thick, red or inflamed skin covered with silvery scales (known as plaques). These plaquesusually itch or feel sore, can crack and bleed, and can occur anywhere on the body.

Psoriasis affects 125 million people worldwide and around 11 million people in Europe.12,13 The type,symptoms and severity of psoriasis may differ from one person to another, with its effects ranging frommild or moderate, to severe. Nearly one-quarter of people with psoriasis have cases that are consideredmoderate to severe.14

Biological therapies represent an advancement in the treatment of moderate to severe plaque psoriasis. Long-term data on available treatment options is important to support healthcare professionals in theirdecision-making about the most appropriate treatment option for patients.

For more information about psoriasis, available treatment options and tools to assess the medical severityof psoriasis please visit http://www.psoriasis360.com

About STELARA (Ustekinumab)

Ustekinumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who failed torespond to, or who have a contraindication to, or are intolerant to other systemic therapies includingciclosporin, methotrexate and PUVA (psoralen plus UVA).15

The recommended dosing regimen for ustekinumab is an initial dose of 45 mg administeredsubcutaneously, followed by a 45 mg dose 4 weeks later, and then every 12 weeks thereafter. For patientswith a body weight of greater than 100 kg the recommended dose is 90 mg administered subcutaneously,followed by a 90 mg dose 4 weeks later, then every 12 weeks thereafter. (In these patients, 45 mg wasalso shown to be efficacious. However, 90 mg resulted in greater efficacy). Consideration should be givento discontinuing treatment in patients who have shown no response up to 28 weeks of treatment.15Ustekinumab is the only subcutaneous treatment for psoriasis available with every 12-week (quarterly)dosing, or as few as four injections per year, following two initial doses.15-17

STELARA is not recommended for use in children and adolescents below age 18 due to a lack of data onsafety and efficacy.

Janssen Biotech, Inc. discovered and developed ustekinumab and has exclusive marketing rights to theproduct in the United States. Janssen pharmaceutical companies have exclusive marketing rights in allcountries outside of the United States.

Important Safety Information14

Ustekinumab is a selective immunosuppressant and may have the potential to increase the risk ofinfections and reactivate latent infections. Serious infections have been observed in patients receivingustekinumab in clinical trials. Do not start ustekinumab during an active infection. If a serious infectiondevelops, monitor patients carefully and stop ustekinumab until the infection resolves. Patients should beevaluated for tuberculosis (TB) infection prior to initiating treatment with ustekinumab.

Ustekinumab is a selective immunosuppressant. Immunosuppressive agents have the potential to increasethe risk of malignancy. Malignancies have been observed in patients receiving ustekinumab in clinical trials.

Caution should be exercised when considering the use of ustekinumab in patients with a history ofmalignancy or when considering continuing treatment in patients who develop a malignancy.

Serious allergic reactions have been reported in the post-marketing setting, in some cases several daysafter treatment. Anaphylaxis and angioedema have occurred. If an anaphylactic or other serious allergicreaction occurs, administration of ustekinumab should be discontinued immediately and appropriatetreatment instituted.

It is recommended that live viral or live bacterial vaccines (such as Bacillus of Calmette and Guérin [BCG])should not be given concurrently with STELARA.

No overall differences in efficacy or safety in patients age 65 and older who received STELARA wereobserved compared to younger patients. Because there is a higher incidence of infections in the elderlypopulation in general, caution should be used in treating the elderly.

Special Warnings and Precautions for Use14

Concomitant immunosuppressive therapy: Caution should be exercised when considering concomitant useof other immunosuppressants and ustekinumab or when transitioning from other immunosuppressivebiologics.

References

1. Paul C et al. Long-term safety and efficacy of ustekinumab in patients with psoriasis inadequately respondingto methotrexate: Week 52 TRANSIT results. Presented at the 21st European Association of Dermatology &Venereology (EADV) congress, Prague 27–30 September 2012. Oral session FC02.1.

2. Reich K et al. Long-term improvement in patient-reported outcomes after transition from methotrexate toustekinumab in moderate to severe psoriasis: TRANSIT Week 52 results. Poster presented at the 21stEuropean Association of Dermatology & Venereology (EADV) congress, Prague 27–30 September 2012. Poster955.

3. Langley R et al. Long term efficacy and safety of ustekinumab in patients with moderate to severe psoriasisthrough 5 years of follow-up: results from the PHOENIX 2 long-term extension. Poster presented at the 21stEuropean Association of Dermatology & Venereology (EADV) congress, Prague 27–30 September 2012. Poster976.

4. Papp K et al. Long term safety of ustekinumab in patients with moderate to severe psoriasis through up to 5years of continuous follow-up. Poster presented at the 21st European Association of Dermatology &Venereology (EADV) congress, Prague 27–30 September 2012. Poster 965.

5. Naldi L et al. Major adverse cardiovascular events in the Psoriasis Longitudinal Assessment and Registry(PSOLAR) study: current status of observations. Presented at the 21st European Association of Dermatology &Venereology (EADV) congress, Prague 27–30 September 2012. Oral session FC02.7.

6. Leonardi C et al. Serious infection events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR)study: current status of observations. Poster presented at the 21st European Association of Dermatology &Venereology (EADV) congress, Prague 27–30 September 2012. Poster 977.

7. Langley R et al. Malignancy events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) study:current dtatus of observations. Poster presented at the 21st European Association of Dermatology &Venereology (EADV) congress, Prague 27–30 September 2012. Poster 973.

8. National Psoriasis Foundation. Related Health concerns: Psoriasis comorbidities. Available at:http://www.psoriasis.org/about-psoriasis/related-conditions. Last accessed September 2012

9. Augustin M et al. A framework for improving the quality of care for people with psoriasis. JEADV 2012; 26(Supplement 4):1–16.

10. The Psoriasis Association. Available at: http://www.psoriasis-association.org.uk/pages/view/about-psoriasis.Last accessed September 2012.

11. National Psoriasis Foundation. Psoriasis types. Available at: http://www.psoriasis.org/about-psoriasis/types.Last accessed September 2012.

12. National Psoriasis Foundation. About Psoriasis: Statistics. Available at: http://www.psoriasis.org/about/stats. Lastaccessed September 2012.

13. Lecluse LL et al. National registries of systemic treatment for psoriasis and the European ‘Psonet’ initiative.Dermatology. 2009;218 (4):347-56.

14. Ustekinumab European Summary of Product Characteristics. Date: March 2012.

15. Wyeth Pharmaceuticals. Enbrel Summary of Product Characteristics.

16. Abbott Laboratories Ltd. Humira Summary of Product Characteristics.

17. Schering-Plough Ltd. Remicade Summary of Product Characteristics.

To view a film of experts discussing the data, please visit:
http://www.brainshark.com/janssencns/PsoriasisInterviews

Janssen