Day: 09/28/2012

Novartis data show AIN457 significantly reduced signs and symptoms in patients with hard-to-treat moderate-to-severe plaque psoriasis

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  • Phase II data show AIN457 given weekly during the first month of treatment improved hand/foot psoriasis at Week 12 (54% of patients vs 19% on placebo)[1] 
  • AIN457 selectively binds to and inhibits interleukin-17A, a key driver of immune-mediated diseases and a promising target for the next generation of therapy[2-4]
  • AIN457 pivotal Phase III trials with more than 3,000 psoriasis patients on track with regulatory submissions expected in 2013
  • Psoriasis on the hands, feet and nails is traditionally difficult-to-treat, causes functional and social disability and can affect up to 55% of psoriasis patients[5],[6] 

Novartis announced today new Phase II data showing AIN457 (secukinumab) may significantly improve moderate-to-severe plaque psoriasis on the hands, feet and nails when used every week for the first month of treatment, compared to placebo[1],[7]. Additional analysis on patients with moderate-to-severe plaque psoriasis also showed that AIN457 may successfully improve quality of life by Week 12 in the study[8].

 

“These new AIN457 data are particularly welcome since they demonstrate significant improvement in the signs and symptoms of patients, even when difficult-to-treat areas are involved,” said Prof. Kristian Reich, one of the study investigators and Professor of Dermatology, Venereology, and Allergology in Hamburg, Germany. “Many patients with hand, foot or nail psoriasis are restricted in their daily life and work because they may not be able to walk or use their hands, negatively impacting their quality of life.”

 

The results will be presented today at the European Academy of Dermatology and Venereology (EADV) 21st Congress, in Prague, Czech Republic. They provide additional insight into the safety and efficacy of AIN457, following the presentation of the study’s primary endpoint at EADV in 2011.

 

The new data from the sub-analyses undertaken on the Phase II study show AIN457 was nearly three times more effective than placebo at reducing moderate-to-severe plaque psoriasis on the hands and/or feet when given every week during the first month of treatment (54.3% of patients vs. 19.2% respectively, p=0.005), as measured by the Investigator’s Global Assessment (IGA)[1]. Patients also benefited if they received AIN457 once every four weeks, with 39.0% experiencing either “clear” or “minimal” psoriasis after 12 weeks of treatment[1]. Another analysis found that these AIN457 treatment schedules also notably reduced the signs and symptoms of finger nail psoriasis compared to placebo[7].

 

The study safety analysis of these data showed a comparable safety profile between treatment and placebo, with the most common adverse events (AEs) observed being infections[1],[7].

 

Other new data presented at EADV in the total moderate-to-severe plaque psoriasis study population show that AIN457 improved skin-related quality of life in 25 times more patients after 12 weeks of treatment when given every week for the first month, compared to placebo (40.8% vs. 1.6%, p<0.001), as measured by the Dermatology Life Quality Index (DLQI)[8]. In this same treatment group, significantly more patients experienced improvements in pain and discomfort compared to placebo (36.2% vs. -1.5%) from baseline; and in anxiety and depression versus placebo (16.3% vs. 6.2%), as measured by EuroQol (EQ-5D)[8]. The effect of psoriasis on patients’ health-related quality of life has been shown to be similar to diseases such as cancer, heart attack, arthritis, type 2 diabetes and depression[9].

 

“These encouraging results show that through its novel mode of action, AIN457 may significantly increase treatment success and improve the quality of life of patients suffering from moderate-to-severe plaque psoriasis,” said John Hohneker, Head of Development for Integrated Hospital Care for the Pharmaceuticals Division of Novartis. “We look forward to receiving the results of the larger-scale and longer-term Phase III studies, which are expected in 2013.”

 

All core pivotal trials for AIN457 in moderate-to-severe plaque psoriasis are on track, involving more than 3,000 patients worldwide, and indicating a high interest from both medical and patient communities. Phase III data in moderate-to-severe plaque psoriasis is expected in 2013, with regulatory submissions to follow shortly thereafter.

 

About the study

Data are based on a double-blind, parallel group, placebo-controlled Phase II study involving 404 patients, which met its primary endpoint of PASI 75 (Psoriasis Area and Severity Index) responses at Week 12[10]. It was designed to evaluate the safety and efficacy of AIN457 in different regimens (weekly for the first month; once every four weeks; or single dose) of 150 mg given subcutaneously[10].

 

The undertaken sub-analyses included assessment of AIN457 treatment efficacy in 131 patients with hand and/or foot psoriasis, often described as palmoplantar psoriasis[1]. All 404 patients were involved in assessing health-related quality of life, and data from 304 patients were used to assess AIN457 treatment efficacy in nail psoriasis[7],[8].

 

About AIN457

AIN457 is a fully human monoclonal antibody inhibiting interleukin-17A (IL-17A), a key pro-inflammatory cytokine. Proof-of-concept and Phase II studies in moderate-to-severe plaque psoriasis and arthritic conditions (psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis) have suggested that AIN457 may provide a new mechanism of action for the treatment of immune-mediated diseases[10-13]. The Phase III programs for these potential indications are ongoing, and first interpretable results are expected in 2013 for moderate-to-severe plaque psoriasis and in 2014 for arthritic conditions. Phase II studies are also ongoing in other areas, including multiple sclerosis.

 

About psoriasis

Approximately 2% of the world’s population, or around 125 million patients, are affected by plaque psoriasis, a chronic disease characterized by thick and extensive skin lesions, called plaques, known to cause itching, scaling and pain[14],[15]. More than one third of patients with plaque psoriasis suffer from its moderate-to-severe form[16].

 

Patients with hand, foot and nail psoriasis endure significantly greater physical disabilities than those whose psoriasis is limited to other parts of the body[5],[6]. This includes functional disability, burning sensations, skin soreness, prolonged duration of psoriasis and the risk of joint involvement and secondary infections[5],[6]. Estimated to affect between 10% and 55% of all psoriasis patients, nail, hand and foot psoriasis is notoriously difficult to treat and often requires systemic treatment such as biologics to maintain an adequate clinical response[5],[6],[17].

 

 

References

1. Paul C, Mroweitz U, Nakayama J et al. Secukinumab, a fully human, anti-interleukin (IL)-17A monoclonal antibody improves signs and symptoms of hand and foot psoriasis: results from a phase II regimen-finding trial. Presented at: 21st Congress of the European Academy of Dermatology and Venereology; 27-30 September, 2012; Prague, Czech Republic. Poster PRA12-0816.

2. Gaffen SL. Structure and signaling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556-67.

3. Ivanov S, Linden A. Interleukin-17 as a drug target in human disease. Trends Pharmacol Sci. 2009;30(2):95-103.

4. Kopf M, Bachmann MF, Marsland BJ. Averting inflammation by targeting the cytokine environment. Nat Rev Drug Discov. 2010;9(9):703-18.

5. Radtke MA, Langenbruch AK, Schafer I et al. Nail psoriasis as a severity indicator: results from the PsoReal study. Patient Relat Outcome Meas. 2011;2:1-6

6. Pettey AA, Balkrishnan R, Rapp et al. Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am Acad Dermatol. 2003;49(2) :271-275.

7. Gottlieb AB, Reich K, Philipp S et al. Secukinumab improves signs and symptoms of nail psoriasis: results from a phase II regimen-finding trial. Presented at: 21st Congress of the European Academy of Dermatology and Venereology; 27-30 September, 2012; Prague, Czech Republic. Poster PRA12-0668.

8. Wilsmann-Theis D, Terui T, Draelos Z et al. Improvement with secukinumab on patient reported skin related quality of life (QoL) and health status among moderate-to-severe plaque psoriasis patients: results from a phase II regimen-finding trial. Presented at: 21st Congress of the European Academy of Dermatology and Venereology; 27-30 September, 2012; Prague, Czech Republic. Poster: PRA12-0822.

9. Rapp SR, Feldman SR, Exum, ML et al. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. 1999;41(3):401-407.Leipe J, Grunke M, Dechant C et al. Role of Th17 cells in human autoimmune arthritis. Arthritis Rheum. 2010;62:2876-2885.

10. Rich P.A. et al. Secukinumab, a new fully human monoclonal anti-Interleukin-17A antibody, in the treatment of moderate-to-severe plaque psoriasis: Interim efficacy and safety data from a phase II regimen-finding trial. Presented at: 20th Congress of the European Academy of Dermatology and Venereology; 20-24 October, 2011; Lisbon, Portugal. Oral presentation FC01.6.

11. Genovese M, Kellner H, Durez P, et al. Secukinumab treatment improves ACR50, HAQ-DI and EULAR remission rates in patients with rheumatoid arthritis. At: EULAR 2012, The Annual European Congress of Rheumatology; 6-9 June 2012, Berlin, Germany. Abstract 2925.

12. Baeten D, Sieper J, Emery P, et al.The anti-il17a monoclonal antibody secukinumab (AIN457) showed good safety and efficacy in the treatment of active ankylosing spondylitis. At: EULAR 2011, The Annual European Congress of Rheumatology, 25-28 May 2011, London, UK. Abstract 0174.

13. McInnes I, Sieper J, Braun J, et al. Anti-Interleukin 17A monoclonal antibody secukinumab reduces signs and symptoms of psoriatic arthritis in a 24-week multicenter, double-blind, randomized, placebo-controlled trial. Presented at: Annual Scientific Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals; 4-9 November 2011; Chicago, IL. Abstract 19541.

14. Raychaudhuri SP, Farber EM. The prevalence of psoriasis in the world. J Eur Acad Dermatol Venereol. 2001;15:16-17.

15. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361:496-509.

16. Herrier R. Advances in the treatment of moderate-to-severe plaque psoriasis. Am J Health-Syst Pharm 2011;68:795-806.

17. Farley E, Masrour S, McKey J et al. Palmoplantar psoriasis: a phenotypical and clinical review with introduction of a new quality-of-life assessment tool. J Am Acad Dermatol. 2009;60(6):1024-1031.

 

Source: Novartis newsletter.

 

 

 

 

BLEEDING RISKS WITH TRIPLE ANTITHROMBOTIC THERAPY, QUANTIFIED

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Compared with an anticoagulant plus antiplatelet monotherapy, triple antithrombotic therapy increased bleeding risk by 40% without reducing risk for thrombotic events.

Patients with both atrial fibrillation (AF) and acute coronary syndromes pose a difficult and frequent clinical conundrum: how to address the need for both anticoagulation and dual antiplatelet therapy without increasing bleeding risk. In this Danish study, investigators used national patient registries of all hospital admissions and prescriptions to study outcomes in 11,480 patients with AF who were hospitalized for myocardial infarction (MI) or percutaneous coronary intervention during a 9-year period.

At baseline, mean patient age was 76, and 61% were men. Patients received various combinations of aspirin, clopidogrel, and vitamin K antagonists (VKAs). At 1 year, the crude incidence rate of fatal or nonfatal bleeding per 100 person-years of therapy was 14.2 for triple therapy and ranged from 7.0 to 10.6 for dual therapy and from 6.6 to 7.0 for monotherapy. The bleeding rate with triple therapy was highest within 30 days after the index admission (22.6 per 100 person-years) but remained higher than with any other combination throughout the study period. In adjusted analyses, compared with dual therapy including VKA, triple therapy conferred a significantly increased risk for bleeding (hazard ratio, 1.41) but no significant benefit for the combined endpoint of cardiovascular death, MI, and ischemic stroke (HR, 1.15).

Comment: This large registry analysis provides unique quantitative data on the relative risks of combined antithrombotic therapies in patients with both atrial fibrillation and coronary artery disease — when each therapy is indicated, but no good studies of the combinations exist. Not surprisingly, the risk for major bleeding with triple antithrombotic therapy is high and sustained over time. New studies (some already initiated) that combine bleeding risk assessment with the efficacy of various dual combinations of agents in these patients are badly needed.

Source: Journal Watch Cardiology

Use of Live-Attenuated Influenza Vaccine for Healthcare Providers.

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A recent guidance statement from the Society for Healthcare Epidemiology of America supports the use of live-attenuated influenza vaccine for most healthcare workers.

Healthcare institutions are being asked to immunize an increasingly higher percentage of healthcare providers against influenza each year, with an eventual target of 90%. The live-attenuated influenza vaccine (LAIV) is an attractive approach for needle-averse individuals, but concerns have persisted about the use of a live vaccine in the healthcare setting.

A recent guidance statement from the Society for Healthcare Epidemiology of America reviews available data on LAIV virus shedding and the risk for secondary transmission of LAIV virus from an immunized individual to another person. The guideline endorses:

  • Use of LAIV as an alternative to the standard inactivated influenza vaccine for healthy, nonpregnant healthcare workers aged <50
  • Restriction on the use of LAIV for healthcare workers who, during the week following vaccination, will have frequent contact with patients receiving care in a protective environment (e.g., a bone marrow transplantation unit)

Comment: This guideline provides further reassurance for healthcare facilities that incorporate LAIV into their immunization programs. It emphasizes that the restriction on LAIV use for healthcare providers working in a protective environment is recommended “as a result of an abundance of caution” and notes that the restriction need not be extended to individuals who have infrequent contact with this patient population.

Sourc: Journal Watch Infectious Diseases

Nuclear medicine pioneer Dr. Henry Wagner passes away.

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September 26, 2012 —Image., a pioneer in the field of nuclear medicine and past president of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), died on September 25 at the age of 85.

The professor emeritus of medicine and radiology at Johns Hopkins University is credited as being one of the founders of nuclear medicine as a scientific and medical specialty and was often called the “Father of Nuclear Medicine.”

In announcing Wagner’s passing, SNMMI President Dr. Frederic Fahey said Wagner’s impact on nuclear medicine is “immeasurable. He was brilliant, visionary, jovial, generous and gracious. He was the kind of man the likes of which we may never see again. He will be missed by many.”

During his career, Wagner conducted groundbreaking research in imaging the perfusion and ventilation of the lungs, kidney and spleen scanning, myocardial perfusion with potassium-43, gated blood pool imaging, and imaging brain receptors with PET.

In an article Wagner wrote for AuntMinnie.comin 2006, he tells how he chose nuclear medicine as his specialty in 1957, five years after graduating from Johns Hopkins University.

“More than any other specialty,” he wrote, “nuclear medicine brought together structure and function, which accounts for the wide acceptance today of combined structural, functional, and biochemical imaging in medicine and biomedical research.”

In 2006, Wagner authored a book titled A Personal History of Nuclear Medicine, in which he reflects on his childhood and family, growing up in Baltimore, and how World War II and the Korean War left lasting impressions on him during his high school, college, and medical school days.

He was well-known for selecting the Image of the Year at the society’s annual meetings, which became a highlight of the event. The image exemplified the most cutting-edge nuclear medicine or molecular imaging research of the day, and demonstrated the ability of the specialty to detect and diagnose disease and help select the most appropriate therapy.

For the first time in 53 years, the 2010 SNM Image of the Year was not chosen by Wagner, who did not attend the annual meeting due to his retirement.

Wagner was also a co-founder of the SNMMI Wagner-Torizuka Fellowship. The two-year fellowship is designed to provide extensive training and experience in nuclear medicine and molecular imaging for Japanese physicians in the early stages of their careers and includes a $24,000 annual stipend. The program is sponsored by Nihon Medi-Physics in Japan and is in its fifth year.

A private funeral service will be held on September 28 at 10 a.m. at the Shrine of the Sacred Heart Church, 5800 Smith Ave., in Baltimore.

In lieu of flowers, the family has asked that memorial donations be made in Wagner’s name to the Johns Hopkins School of M A memorial service will be held for colleagues to celebrate Wagner’s life on November 3 at Johns Hopkins University. Additional details regarding the memorial service will be distributed and posted on SNMMI’s website when available.edicine or the Johns Hopkins Bloomberg School of Public Health.

Source: Auntminnie

 

Suicide Surpasses Car Crashes as Leading Cause of Injury-Related Mortality.

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Suicide is now the top cause of injury-related mortality in the U.S., surpassing deaths from motor vehicle accidents, according to a study published in the American Journal of Public Health.

Using data from the National Center for Health Statistics, researchers analyzed underlying causes of injury-related death from 2000 through 2009. Among the main findings:

  • The total injury mortality rate rose 10% during that period.
  • The rate of motor vehicle accidents declined 25%, while the suicide rate climbed 15%.
  • Unintentional poisoning surpassed homicide to become the third leading cause of injury mortality, increasing 128%.
  • Unintentional falls rose 71%, making them the fourth leading cause of injury mortality.
  • Homicide fell to the fifth leading cause, dropping 8%.

The authors conclude: “Comprehensive and sustained traffic safety measures have apparently substantially diminished the motor vehicle traffic mortality rate, and similar attention and resources are needed to reduce the burden of other injury.”

Source : American Journal of Public Health

 

Physicians May Help Prevent Road Crashes.

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Physician warnings to potentially unfit drivers may reduce road crashes, according to a New England Journal of Medicine study.

Researchers examined data on patients in Ontario, Canada, where beginning in 2006, physicians were offered a financial incentive to warn medically unfit patients against driving. From 2006 through 2009, over 100,000 patients received warnings.

The annual rate of crashes in which the patient was the driver and presented to the emergency department decreased from 4.76 events per 1000 people in the period before warnings to 2.73 per 1000 in the year afterward. This reduction was significant, although the post-warning crash rate remained above the rate in the general population. Patients with dementia, stroke, depression, fainting, or epilepsy saw the greatest reductions; all age groups benefited.

In the post-warning period, return visits to physicians decreased and ED visits for depression increased — suggesting that such warnings, while injury-preventing, may “exacerbate mood disorders and compromise the doctor-patient relationship,” the authors note.

Source: NEJM

 

Low Blood Pressure Isn’t Associated with Lower Mortality in Patients with Newly Diagnosed Diabetes.

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Type 2 diabetic patients whose blood pressure was <110/75 had excess risk for mortality at 3.5 years.

An American Diabetes Association guideline recommends that “most patients with diabetes” receive treatment to reach a systolic blood pressure (SBP) target of <130 mm Hg (although exceptions are allowed for “higher or lower SBP targets” based on patients’ characteristics and treatment responses) and a diastolic BP (DBP) target of <80 mm Hg (Diabetes Care 2012; 35 (Suppl 1):S11). Little evidence, however, supports these recommendations. In this retrospective study, investigators used the U.K. General Practice Research Database to examine the effects of SBP and DBP on all-cause mortality in 126,000 adults with newly diagnosed type 2 diabetes.

BP was determined during the first year after diagnosis of diabetes. After median follow-up of 3.5 years, 20% of patients had died. In patients with cardiovascular (CV) disease, those whose SBP was lower than 110 mm Hg were significantly more likely to die than were those whose SBP was 130 to 139 mm Hg (hazard ratio, 2.8); mortality among patients with SBP of 110 to 129 mm Hg was similar to that among patients with SBP of 130 to 139. Participants whose DBP was 70 to 74 mm Hg and those whose DBP was <70 mm Hg were significantly more likely to die than were those whose DBP was 80 to 84 mm Hg (HRs, 1.3 and 1.9, respectively). Similar results were found in patients without CV disease.

Comment: In this study, BP lower than 130/80 mm Hg was not associated with lower risk for 3.5-year all-cause mortality in patients with newly diagnosed type 2 diabetes. In fact, BP lower than 110/75 mm Hg was associated with excess risk. Notably, these observational results are similar to those from the randomized ACCORD blood pressure trial, which showed that, in patients with long-standing type 2 diabetes at high risk for adverse CV events, an SBP target of <120 mm Hg, compared with a target of <140 mm Hg, did not lower incidence of a composite endpoint of fatal and nonfatal CV events.

Source: Journal Watch General Medicine

Featured in Journal Watch: Strict Adherence to Antiretroviral HIV Therapy Is Best.

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In a group of patients on longstanding antiretroviral therapy, nonadherence — although not associated with a rebound in plasma viral loads — was associated with a significant increase in cell-associated HIV RNA levels. The authors conclude that modest nonadherence leads to HIV replication cycles not reflected in viral-load assays.

Writing in Journal Watch HIV/AIDS Clinical Care, Keith Henry says: “Although many patients and clinicians are under the impression that current ART regimens have some degree of forgiveness, the goal for therapy continues to be 100% adherence.”

Source:Journal Watch HIV/AIDS Clinical Care

 

Many Healthcare Workers, Pregnant Women Forgo Influenza Vaccination.

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Only about two thirds of healthcare personnel were immunized against influenza during the 2011–2012 season, according to an MMWR study.

A CDC survey of some 2300 healthcare personnel recruited from two Internet sources found the following vaccination rates:

  • by occupation: 86% of physicians, 78% of nurses, and 63% of other healthcare personnel (e.g., dentists, clerical workers, cleaning staff)
  • by work setting: 77% in hospitals, 68% in physician offices, 52% in long-term-care facilities
  • by employer policy: 95% in hospitals that required influenza vaccination and 68% in those where it was not required

The three most common reasons for not getting vaccinated were belief that it wasn’t necessary, concern about effectiveness, and concern about side effects.

In a separate survey of nearly 1700 pregnant women, 47% reported receiving influenza vaccination during 2011–2012. Vaccination rates were more than six times higher among women whose healthcare providers recommended and offered vaccination than among those whose providers did neither.

Source: MMWR

 

Progesterone Levels Can Reliably Predict Viability in Early Pregnancy.

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In evaluating early pregnancy, a single progesterone measurement can rule out viability, depending on the cutoff levels used and whether ultrasound is available, according to a BMJ meta-analysis.

Researchers examined data from 26 cohort studies including some 9500 pregnant women, some with symptoms and inconclusive ultrasound results, and others with only symptoms.

In studies with inconclusive ultrasound results, a progesterone cutoff level between 3.2 and 6 ng/mL gave a sensitivity of 75% and a specificity of 98% for predicting a nonviable pregnancy.

In studies with symptoms alone, a progesterone cutoff of 10 ng/mL gave a sensitivity of 67% and a specificity of 96%.

The authors conclude that the test “is more accurate when it follows an inconclusive ultrasound.”

Source: BMJ