Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study

Objectives. To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA. Methods. Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures. Results. A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-a use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously. Conclusion. Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously. Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT0175263

Secukinumab versus adalimumab for psoriatic arthritis: comparative effectiveness up to 48 weeks using a matching-adjusted indirect comparison

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG

Trends in typologies of concurrent alcohol, marijuana, and cigarette use among US adolescents: An ecological examination by sex and race/ethnicity

Substance use during adolescence is a public health concern due to associated physical and behavioral health consequences. Such consequences are amplified among concurrent substance users. Although sex and racial/ethnic differences in single-substance use have been observed, the current literature is inconclusive as to whether differences exist in the prevalence of concurrent use. The current study used data from the 2011–2014 National Survey on Drug Use and Health to examine typologies (single and concurrent patterns) of alcohol, marijuana, and cigarette use among current adolescent users age 12–18 by sex and race/ethnicity. Participants were 14,667 White, Hispanic, African American, Asian, and Native American adolescents. The most common typology was alcohol only, followed by concurrent use of alcohol and marijuana. Weighted prevalence estimates indicated that adolescent females were more likely to be current users of alcohol only, whereas male adolescents were more likely to belong to all other typologies. Compared to Whites, racial/ethnic minorities had larger proportions of marijuana only users and were generally less likely than or equally likely to be concurrent users. One exception was for African American adolescents, who were more likely to be alcohol and marijuana users than their White counterparts. Results suggest that concurrent substance use is common among U.S. adolescents, making up over 40% of past-month use, but typologies of use vary by sex and race/ethnicity. Preventive interventions should consider all typologies of use rather than only single substance exposures and address patterns of use that are most pertinent to adolescents based on sex and race/ethnicity

Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3)

Background: The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study (ClinicalTrials.gov NCT01989468). Methods: Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naïve, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ). Results: Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naïve and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported. Conclusions: Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously

The Effect of Black Tax on Employee Engagement: The Mediating Role of Idiocentrism-Allocentrism-A Case of Pharmaceutical Industry in Zimbabwe

Employees in the Pharmaceutical industry are coming late to work and knocking off early. These actions unveiled by the employees are likely to incur economic costs on the employer, occasioned by low employee productivity. Owners of production have expressed concern over the general low staff morale in the pharmaceutical sector. While most studies have concentrated on internal job-related factors as drivers of employee engagement, this study seeks to assess employee engagement as being influenced by black tax, an external factor. The main aim of the research was to establish the influence of black tax on employee engagement, being mediated by idiocentrism-allocentrism, particularly focussing on the pharmaceutical manufacturing and retailing industry in Bulawayo, Zimbabwe. The study employed the philosophical approach of pragmatism to guide the whole research. The researcher adopted a multi-stage sampling technique supported by the census technique to pick participants from the population. Closed and open-ended questionnaires were used to collect data from qualified pharmacists who are working in both the manufacturing and retailing industry in Bulawayo. Statistical Package for Social Sciences v23 (Process v3.5 by Andrew F. Hayes) was used to test the hypothesized relationship among variables. Qualitative data were analyzed using thematic analysis. The results suggest that black tax directly influence employee engagement in the presence of a mediator (idiocentrism-allocentrism). Furthermore, the results indicate that the indirect coefficient was partially significant, which means that idiocentrism-allocentrism has a partial influence on employee engagement. The researchers recommend that management should ensure that employees are motivated all the time. They should implement an open-door policy so that employees can share their issues that affect their engagement level at work

Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis. Methods: In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01752634. Findings: Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6·81, 95% CI 3·42–13·56; p<0·0001), 150 mg (51 [51%] patients; 6·52, 3·25–13·08; p<0·0001), and 75 mg (29 [29%] patients; 2·32, 1·14–4·73; p=0·0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. Interpretation: Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder

Presentations of perforated colonic pathology in patients with polymyalgia rheumatica: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Polymyalgia rheumatica is an increasingly common disease in older people, which gives rise to arthralgia and is mainly treated with corticosteroids. Patients in this age group also have a higher incidence of other co-morbidities including colonic pathology. Corticosteroid usage may mask signs of sepsis or complications secondary to intra-abdominal pathology, thereby delaying diagnosis and treatment, with eventual adverse outcome. These two cases highlight the importance of awareness and prompt recognition of this condition in order to avoid significant morbidity and mortality.</p> <p>Case presentation</p> <p>Case 1</p> <p>A 73-year-old Caucasian woman with a diagnosis of polymyalgia presented with symptoms of an exacerbation in her right hip joint. Despite standard therapy with corticosteroids she failed to improve and started to develop features of widespread sepsis. Specific questioning revealed that, at the very onset of her symptoms, she had experienced mild diarrheal symptoms. Investigations revealed perforated diverticular disease with a peri-femoral abscess.</p> <p>Case 2</p> <p>A 69-year-old Caucasian woman with polymyalgia presented with left thigh pain and weakness associated with weight loss. A diagnosis of exacerbation of polymyalgia rheumatica was made and she was treated with corticosteroid therapy. Shortly afterwards she was admitted with generalized peritonitis. Laparotomy revealed a retroperitoneal abscess secondary to a perforated sigmoid colonic tumor.</p> <p>Conclusions</p> <p>Patients with polymyalgia may have perforated colonic diverticular disease which mimics their rheumatic pathology. In such cases steroid therapy, which is the mainstay of polymyalgia therapy, can be detrimental. Primary and hospital practitioners are encouraged to be vigilant regarding non-specific gastrointestinal symptoms and consider alternative diagnoses in those patients whose symptoms do not resolve with standard therapy, as this can lead to an overall better outcome.</p