Ustekinumab for the treatment of moderate to severe psoriasis

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of ustekinumab for the treatment of moderate to severe psoriasis based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's main evidence came from three randomised controlled trials (RCTs), of reasonable methodological quality and measuring a range of clinically relevant outcomes. Higher proportions of participants treated with ustekinumab (45 mg and 90 mg) than with placebo or etanercept achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) after 12 weeks. There were also statistically significant differences in favour of ustekinumab over placebo for PASI 50 and PASI 90 results, and for ustekinumab over etanercept for PASI 90 results. A weight-based subgroup dosing analysis for each trial was presented, but the methodology was poorly described and no statistical analysis to support the chosen weight threshold was presented. The manufacturer carried out a mixed treatment comparison (MTC); however, the appropriateness of some of the methodological aspects of the MTC is uncertain. The incidence of adverse events was similar between groups at 12 weeks and withdrawals due to adverse events were low and less frequent in the ustekinumab than in the placebo or etanercept groups; however, statistical comparisons were not reported. The manufacturer's economic model of treatments for psoriasis compared ustekinumab with other biological therapies. The model used a reasonable approach; however, it is not clear whether the clinical effectiveness estimates from the subgroup analysis, used in the base-case analysis, were methodologically appropriate. The base-case incremental cost-effectiveness ratio for ustekinumab versus supportive care was 29,587 pounds per quality-adjusted life-year (QALY). In one-way sensitivity analysis the model was most sensitive to the number of hospital days associated with supportive care, the cost estimate for intermittent etanercept 25 mg and the utility scores used. In the ERG's scenario analysis the model was most sensitive to the price of ustekinumab 90 mg, the proportion of patients with baseline weight > 100 kg and the relative risk of intermittent versus continuous etanercept 25 mg. In the ERG's probabilistic sensitivity analysis ustekinumab had the highest probability of being cost-effective at conventional NICE thresholds, assuming the same price for the 45-mg and 90-mg doses; however, doubling the price of ustekinumab 90 mg resulted in ustekinumab no longer dominating the comparators. In conclusion, the clinical effectiveness and cost-effectiveness of ustekinumab in relation to other drugs in this class is uncertain. Provisional NICE guidance issued as a result of the STA states that ustekinumab is recommended as a treatment option for adults with plaque psoriasis when a number of criteria are met. Final guidance is anticipated in September 2009.

Positive changes in self-management and disease severity following climate therapy in people with psoriasis

The aim of this study was to investigate the impact of climate therapy on self-management in people with psoriasis. This was a prospective study of 254 adults with chronic psoriasis who participated in a 3-week climate therapy (CT) programme. The 8-scale Health Education Impact Questionnaire (heiQ) was completed at baseline, after 3 weeks of CT, and 3 months later. Change was assessed using paired sample t-tests mean (95% confidence interval) change scores (range 1-4). All heiQ scales showed statistically significant improvement after 3 weeks of CT. The greatest improvement was in Health-directed activity, followed by Emotional distress, and Skill and technique acquisition. At the 3-month follow-up, only the Emotional distress scale remained improved. In addition, disease severity (self-administered PASI; SAPASI) improved significantly from before CT to 3 weeks and 3 months after CT. This study suggests that CT provides a range of benefits that are important to people with psoriasis, particularly in the short term. A challenge is how to achieve long-term benefits.

Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways

There is now evidence that depression, as characterized by melancholic symptoms, anxiety, and fatigue and somatic (F&S) symptoms, is the clinical expression of peripheral cell-mediated activation, inflammation and induction of oxidative and nitrosative stress (IO&NS) pathways and of central microglial activation, decreased neurogenesis and increased apoptosis. This review gives an explanation for the multiple “co-morbidities” between depression and a large variety of a) brain disorders related to neurodegeneration, e.g. Alzheimer’s, Parkinson’s and Huntington’s disease, multiple sclerosis and stroke; b) medical disorders, such as cardiovascular disorder, chronic fatigue syndrome, chronic obstructive pulmonary disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, inflammatory bowel disease, irritable bowel syndrome, leaky gut, diabetes type 1 and 2, obesity and the metabolic syndrome, and HIV infection; and c) conditions, such as hemodialysis, interferon-α-based immunotherapy, the postnatal period and psychosocial stressors. The common denominator of all those disorders/conditions is the presence of microglial activation and/or activation of peripheral IO&NS pathways. There is evidence that shared peripheral and / or central IO&NS pathways underpin the pathophysiology of depression and the previously mentioned disorders and that activation of these IO&NS pathways contributes to shared risk. The IO&NS pathways function as a smoke sensor that detect threats in the peripheral and central parts of the body and signal these threats as melancholic, anxiety, and fatigue and somatic (F&S) symptoms. The presence of concomitant depression is strongly associated with a lower quality of life and increased morbidity and mortality in medical disorders. This may be explained since depression contributes to increased (neuro)inflammatory burden and may therefore drive the inflammatory and degenerative progression. It is concluded that the activation of peripheral and / or central IO&NS pathways may explain the co-occurrence of depression with the above disorders. This shows that depression belongs to the spectrum of inflammatory and degenerative disorders.

Physical comorbidities in men with mood and anxiety disorders: a population-based study

Background : The mind-body nexus has been a topic of growing interest. Further data are however required to understand the specific relationship between mood and anxiety disorders and individual physical health conditions, and to verify whether these psychiatric disorders are linked to overall medical burden.
Methods : This study examined data collected from 942 men, 20 to 97 years old, participating in the Geelong Osteoporosis Study. A lifetime history of mood and anxiety disorders was identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). The presence of medical conditions (lifetime) was self-reported and confirmed by medical records, medication use or clinical data. Anthropometric measurements and socioeconomic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Logistic regression models were used to test the associations.
Results : After adjustment for age, socioeconomic status, and health risk factors (body mass index, physical activity and smoking), mood disorders were associated with gastro oesophageal reflux disease (GORD), recurrent headaches, blackouts and/or epilepsy, liver disorders and pulmonary disease in older people, whilst anxiety disorders were significantly associated with thyroid, GORD and other gastrointestinal disorders, and psoriasis. Increased odds of high medical burden were associated with both mood and anxiety disorders.
Conclusions : Our study provides further population-based evidence supporting the link between mental and physical illness in men. Understanding these associations is not only necessary for individual management, but also to inform the delivery of health promotion messages and health care.

Suicidal ideation and physical illness: Does the link lie with depression?

Objective
Medical illness is a risk factor for suicidality; however, disorder-specific risks are not well-known and these relationships are often explained by major depressive disorder (MDD). We aimed to investigate the relationship between suicidal ideation, MDD and medical illnesses in an age-stratified, population-based sample of men participating in the Geelong Osteoporosis Study.

Methods
Suicidal ideation and medical conditions were self-reported. Medical conditions were confirmed by medical records, medication use or clinical data where possible. MDD was determined using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition.

Results
Of the 907 men, 8.5% reported suicidal ideation. Thyroid disorders (OR 3.85, 95%CI 1.2–12.1), syncope and seizures (OR 1.96, 95%CI 1.1–3.5), liver disorders (OR 3.53, 95%CI 1.1–11.8; younger men only) and alcoholism (OR 2.15, 95%CI 1.1–4.4) were associated with increased odds of suicidal ideation, independent of age and MDD. Major vascular events doubled the odds of suicidal ideation but this was explained by MDD. No association was evident with high medical burden, musculoskeletal disease, metabolic factors, gastrointestinal disorders, headaches, cardiovascular disease, COPD, cancer and psoriasis.

Conclusion
Health care professionals should focus on identification, assessment and management of suicidal ideation in the medically ill in patients both with and without MDD.