A series of data presentations released today 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 framework(9) (White Paper) to improve standards of care for patients, especially in terms of access to the right targeted treatment appropriate for their disease severity.
Study design and results
Design: A 52 week, open-label, Phase 4 study of 489 patients designed to compare two methods of transitioning patients from methotrexate to ustekinumab. The first was discontinuation of methotrexate with immediate initiation of ustekinumab and the second was initiation of ustekinumab with overlap and gradual dose reduction of methotrexate over four weeks.
Results: Ustekinumab was well tolerated, with 8% of patients in each transition arm experiencing a serious adverse event (AE), and associated with sustained efficacy; 76% and 77% of patients, in the methotrexate 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 (PASI 75) at Week 52. The data showed there was no difference in terms of the number and types of AE or efficacy outcomes, whether given ustekinumab1 after immediate cessation of methotrexate or if methotrexate is gradually withdrawn over 4 weeks.
Design: 1,230 patients with moderate-to-severe plaque psoriasis were randomised to receive ustekinumab 45 mg or 90 mg at weeks 0, 4 and every 12 weeks thereafter, or placebo at weeks 0 and 4. Patients initially randomised to placebo at baseline were assigned to cross over to either ustekinumab 45 mg or 90 mg at weeks 12, 16 and every 12 weeks thereafter. Investigators were permitted to adjust ustekinumab dosing 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 achieved and maintained in the overall population; 76.5% and 78.6% of patients who received STELARA 45 mg and 90 mg, respectively, achieved a PASI 75 response at the end of the treatment period. The safety profile of ustekinumab was generally comparable between patients who received 45 mg or 90 mg, with or without dose adjustments.(3)
*PHOENIX 2 study design involved a revised dosing schedule for partial responders which is not included in the 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 of overall and targeted adverse events were analysed by ustekinumab dose received (45 mg or 90 mg) and by year of follow-up (Year 1 to 5) to evaluate potential dose-response or impact of increasing duration of exposure.
Results: Analyses included 3,117 patients with a total of 8.998 PY of follow-up. Rates of safety events were generally comparable between patients who received 45 mg and 90 mg; and generally consistent over time from Year 1 through 5. The overall safety profile of ustekinumab remained stable in adults with moderate-to-severe plaque psoriasis receiving up to five years of ustekinumab treatment. No effect of dose and no effect of increasing duration of exposure were observed.(4)
Design: A disease-based registry study that captures multiple forms of psoriasis therapy that is planned to enroll approximately 12,000 patients. In August 2011, 9,495 patients were available in the last annual data extract reflecting 13,733 PY of exposure. Patients that are eligible for systemic therapies, including ustekinumab and infliximab, are enrolled and followed biannually. Results: Preliminary findings on rates of infection, malignancy (excluding non-melanoma skin cancers) and major 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 centres internationally.(5-7)
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 in patches of thick, red or inflamed skin covered with silvery scales (known as plaques). These plaques usually 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 from mild or moderate, to severe. Nearly one-quarter of people with psoriasis have cases that are considered moderate 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 their decision-making about the most appropriate treatment option for patients.
For more information about psoriasis, available treatment options and tools to assess the medical severity of psoriasis please visit www.psoriasis360.com
About STELARA (Ustekinumab)
Ustekinumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA (psoralen plus UVA).(15)
The recommended dosing regimen for ustekinumab is an initial dose of 45 mg administered subcutaneously, followed by a 45 mg dose 4 weeks later, and then every 12 weeks thereafter. For patients with 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 was also shown to be efficacious. However, 90 mg resulted in greater efficacy).
Consideration should be given to discontinuing treatment in patients who have shown no response up to 28 weeks of treatment.(15) Ustekinumab 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 on safety and efficacy.
Janssen Biotech, Inc. discovered and developed ustekinumab and has exclusive marketing rights to the product in the United States. Janssen pharmaceutical companies have exclusive marketing rights in all countries outside of the United States.
Important Safety Information(14)
Ustekinumab is a selective immunosuppressant and may have the potential to increase the risk of infections and reactivate latent infections. Serious infections have been observed in patients receiving ustekinumab in clinical trials. Do not start ustekinumab during an active infection. If a serious infection develops, monitor patients carefully and stop ustekinumab until the infection resolves. Patients should be evaluated for tuberculosis (TB) infection prior to initiating treatment with ustekinumab.
Ustekinumab is a selective immunosuppressant. Immunosuppressive agents have the potential to increase the risk of malignancy. Malignancies have been observed in patients receiving ustekinumab in clinical trials.
- Paul C et al. Long-term safety and efficacy of ustekinumab in patients with psoriasis inadequately responding to 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.
- Reich K et al. Long-term improvement in patient-reported outcomes after transition from methotrexate to ustekinumab in moderate to severe psoriasis: TRANSIT Week 52 results. Poster presented at the 21st European Association of Dermatology & Venereology (EADV) congress, Prague 27–30 September 2012. Poster 955.
- Langley R et al. Long term efficacy and safety of ustekinumab in patients with moderate to severe psoriasis through 5 years of follow-up: results from the PHOENIX 2 long-term extension. Poster presented at the 21st European Association of Dermatology & Venereology (EADV) congress, Prague 27–30 September 2012. Poster 976.
- Papp K et al. Long term safety of ustekinumab in patients with moderate to severe psoriasis through up to 5 years of continuous follow-up. Poster presented at the 21st European Association of Dermatology & Venereology (EADV) congress, Prague 27–30 September 2012. Poster 965.
- 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.
- 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.
- 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.
- National Psoriasis Foundation. Related Health concerns: Psoriasis comorbidities. Available at: http://www.psoriasis.org/about-psoriasis/related-conditions. Last accessed September 2012
- Augustin M et al. A framework for improving the quality of care for people with psoriasis. JEADV 2012; 26 (Supplement 4):1–16.
- The Psoriasis Association. Available at: http://www.psoriasis-association.org.uk/pages/view/about-psoriasis. Last accessed September 2012.
- National Psoriasis Foundation. Psoriasis types. Available at: http://www.psoriasis.org/about-psoriasis/types. Last accessed September 2012.
- National Psoriasis Foundation. About Psoriasis: Statistics. Available at: www.psoriasis.org/about/stats. Last accessed September 2012.
- Lecluse LL et al. National registries of systemic treatment for psoriasis and the European ‘Psonet’ initiative. Dermatology. 2009;218 (4):347-56.
- Ustekinumab European Summary of Product Characteristics. Date: March 2012.
- Wyeth Pharmaceuticals. Enbrel Summary of Product Characteristics.
- Abbott Laboratories Ltd. Humira Summary of Product Characteristics.
- Schering-Plough Ltd. Remicade Summary of Product Characteristics.