Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study.

Brodalumab, an interleukin-17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open-label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the long-term safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician's discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108-week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis-related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108-week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment-related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn's disease were observed in this study. Serious treatment-related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti-brodalumab-binding antibodies or brodalumab-neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long-term efficacy and safety of brodalumab were demonstrated over 108 weeks.

Comprehensive long-term safety of adalimumab from 18 clinical trials in adult patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Adalimumab (Humira® , AbbVie Inc., North Chicago, IL, U.S.A.) is a fully human monoclonal antibody specific for tumour necrosis factor-α that is approved to treat adults with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: To assess long-term safety for patients with psoriasis receiving adalimumab in clinical studies. METHODS: Adalimumab safety data from adults with psoriasis who received at least one adalimumab dose in 18 clinical trials were evaluated. Adalimumab was delivered subcutaneously in all treatment regimens. Treatment-emergent adverse events (AEs) were collected from the first dose to 70 days after the last dose or cut-off date (31 December 2015). AE incidence rates were expressed as events per 100 patient-years (E/100 PYs) of adalimumab exposure. Standardized incidence ratios (SIRs) for malignancies and standardized mortality ratios (SMRs) were calculated. RESULTS: Cumulative exposure was 5429·7 PYs in 3727 patients. Overall, there were 16 536 AEs (304·6 E/100 PYs). The most common AEs were nasopharyngitis, upper respiratory infection and headache (23·7, 12·9 and 7·9 E/100 PYs, respectively). Incidence rates for serious infections, tuberculosis and opportunistic infections were 1·8, 0·3 and 0·02 E/100 PYs, respectively. Incidence of malignancy excluding nonmelanoma skin cancer (NMSC) was 0·8 E/100 PYs [SIR 0·86, 95% confidence interval (CI) 0·58-1·23]. Incidences of NMSC and melanoma were 0·6 and 0·2 E/100 PYs, respectively. The SIR was 1·55 (95% CI 1·10-2·13) for NMSC and 3·04 (95% CI 1·11-6·62) for melanoma. The SMR was 0·34 (95% CI 0·16-0·65). CONCLUSIONS: AE rates remained stable in this analysis of patients with psoriasis receiving adalimumab; no new safety signals were identified compared with earlier analyses.

Adalimumab treatment in Japanese patients with generalized pustular psoriasis: Results of an open-label phase 3 study.

A phase 3, multicenter, open-label, 52-week study investigated the efficacy and safety of adalimumab 80 mg at week 0 followed by adalimumab 40 mg every other week (option to escalate to 80 mg when necessary) in Japanese patients with generalized pustular psoriasis (GPP). Adults (aged 15-75 years) with GPP, total skin score (overall erythema area, erythema area with pustules, and edema area) of 3 or more, and erythema with pustules (skin score, ≥1) based on the 2014 Japanese Dermatological Association severity index of GPP were enrolled. The primary efficacy end-point was clinical response at week 16 (non-responder imputation), defined as achieving remission (total skin score, 0) or improvement from baseline (reduction of ≥1 point from a baseline total skin score of 3 or ≥2 points from a baseline total skin score of ≥4). Of 10 enrolled patients (mean disease duration, 10.6 years), seven patients, including three with the dose escalated to 80 mg every other week before week 15, achieved clinical response at week 16, and five achieved clinical response at week 52. Mean change from baseline total GPP score was -4.6 at week 16 (n = 8) and -6.0 at week 52 (n = 5); change in total skin score was -3.1 (n = 8) and -4.2 (n = 5), respectively. Nine patients experienced one or more adverse events and three experienced serious adverse events. The most common adverse events were nasopharyngitis, pruritus and hypoalbuminemia. In conclusion, adalimumab was effective and well tolerated for up to 52 weeks in the treatment of Japanese patients with GPP.

Respiratory Tract Infections in Patients With Inflammatory Bowel Disease: Safety Analyses From Vedolizumab Clinical Trials.

BACKGROUND AND AIMS: Vedolizumab, a humanised monoclonal antibody for the treatment of inflammatory bowel disease, selectively blocks gut lymphocyte trafficking. This may reduce the risk of respiratory tract infections [RTIs] compared with systemic immunosuppressive therapies. To assess this possibility, we evaluated the rates of RTIs in clinical trials of vedolizumab. METHODS: Patient-level data from Phase 3 randomised controlled trials [RCTs] of vedolizumab in ulcerative colitis [UC; GEMINI 1] and Crohn's disease [CD; GEMINI 2], and a long-term safety study [UC and CD] were pooled. Cox proportional hazards models were used to estimate the incidence of upper RTIs [URTIs] and lower RTIs [LRTIs] with adjustment for significant covariates. RESULTS: In the RCTs [n = 1731 patients], the incidence of URTIs was numerically higher in patients receiving vedolizumab compared with those receiving placebo, although this difference was not statistically significant (38.7 vs 33.0 patients per 100 patient-years; hazard ratio [HR] 1.12; 95% confidence interval [CI]: 0.83-1.51; p = 0.463). The rate of LRTIs, including pneumonia, was numerically lower in the vedolizumab versus the placebo group: this difference was not statistically significant (7.7 vs 8.5 per 100 patient-years [HR 0.85; 95% CI: 0.48-1.52; p = 0.585]). Both URTIs and LRTIs were more frequent in patients with CD compared with UC. Most RTIs in patients receiving vedolizumab were not serious and did not require treatment discontinuation. CONCLUSIONS: Vedolizumab therapy was not associated with an increased incidence of respiratory tract infection compared with placebo.

[Impact of glucagon-like peptide-1 receptor agonists on nasopharyngitis and upper respiratory tract infection among patients with type 2 diabetes: a network meta-analysis].

OBJECTIVE: To systematically review the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on two common respiratory system adverse events (RSAE: nasopharyngitis and upper respiratory tract infection) among type 2 diabetes (T2DM). METHODS: Medline, Embase, Clinical trials and Cochrane library were searched from inception through May 2015 to identify randomized clinical trials(RCTs) assessed safety of GLP-1RAs versus placebo or other anti-diabetic drugs in T2DM. Network meta-analysis within a Bayesian framework was performed to calculate odds ratios for the incidence of RSAE. RESULTS: In the study, 50 RCTs were included, including 13 treatments: 7 GLP-1RAs (exenatide, exenatide-long-release-agent, liraglutide, lixisenatide, taspoglutide, albiglutide and dulaglutide), placebo and 5 traditional anti-diabetic drugs(insulin, metformin, sulfonylureas, sitagliptin and thiazolidinediones ketones). Compared with insulin, taspoglutide significantly decreased the incidence of nasopharyngitis (OR=0.67, 95%CI: 0.46-0.96). Significant lowering effects on upper respiratory tract infection were found when taspoglutide versus placebo (OR=0.57, 95%CI: 0.34-0.99) and insulin (OR=0.39, 95%CI: 0.23-0.73). The result from the network meta-analysis based on Bayesian theory could be used to rank all the treatments included, which showed that taspoglutide ranked last with minimum risk on nasopharyngitis and upper respiratory tract infection. CONCLUSION: Taspoglutide was associated with significantly lowering effect on RSAE.

[Monitoring of microflora localized at the pharyngeal tonsil surface in the children residing in the city of Chelyabinsk and presenting with chronic adenoiditis].

The objective of the present retrospective study based on the analysis of 791 medical cards was to investigate microflora localized at the pharyngeal tonsil surface in the children living in the city of Chelyabinsk and presenting with exacerbation of chronic adenoiditis. 66% of the patients with this condition were 4-6 year old children. The most commonly documented were the associations composed of resident species S. alpha-haemoliticus and S. epidermidis together with pathobiontic S. aureus. S. beta-haemoliticus and S. pneumoniae occurred most frequently whereas H. influenza and some representatives of the genus Enterobacteriaceae were less numerous. Fungi of the genus Candida were identified in 25.4% of the samples at a titer above 10^4. In 23.7% of the cases, these fungi were found in the associations with S. aureus which resulted in mutual potentiation of the pathogenicity factor.

[The possibilities for the treatment of exudative otitis media in the children presenting with chronic adenoiditis].

The objective of the present study was to improve the effectiveness of medicamental therapy of exudative otitis media in the children with recurrent and chronic adenoiditis. It was shown that the use of fluifort (carbocysteine lysine salt) for the treatment of exudative otitis media in the children presenting with chronic adenoiditis is a more effective approach in comparison with the expectant management. It is concluded that the application of carbocysteine lysine salt in combination with the mometasone furoate nasal spray ensures the rapid elimination of the symptoms of adenoiditis and significantly accelerates the resolution of exudative otitis media compared with the monotherapeutic treatment.

Over-prescribing of antibiotics and imaging in the management of uncomplicated URIs in emergency departments.

BACKGROUND: Unnecessary use of resources for common illnesses has substantial effect on patient care and costs. Evidence-based guidelines do not recommend antibiotics or imaging for uncomplicated upper respiratory infections (URIs). The objective of the current study was to examine medical care providers' compliance with guidelines in treating uncomplicated URIs in emergency departments (EDs) in the US. METHODS: Nationally representative data from the NHAMCS 2007 and 2008 were used. Uncomplicated URIs were identified through ICD-9 codes of nasopharyngitis, laryngitis, bronchitis, URI not otherwise specified and influenza involving upper respiratory tract. Exclusion criteria were concurrent comorbidities, follow-up visits, and age < 18 or >64 years. Most frequently prescribed classes of antibiotics were identified. Multivariate analyses were conducted to identify the factors associated with the prescribing of antibiotics and use of imaging studies. RESULTS: In 2007 and 2008, there were 2.2 million adult uncomplicated URI visits without any other concurrent diagnoses in EDs in the US. Approximately 52% were given antibiotic prescriptions, over one-third of which were macrolides, and nearly half of the visits performed imaging studies. About 51% had a diagnosis of bronchitis, 35% URI NOS, 9% nasopharyngitis, laryngitis or influenza, and 4% multiple URI diagnoses. The diagnosis of bronchitis, fever at presentation, older ages, male gender, longer waiting time, and metropolitan areas were associated with a greater likelihood of prescribing antibiotics or imaging studies, controlling for confounding factors. CONCLUSION: Despite the recommendations and campaign efforts by the CDC and many medical associations, the prescribing of antibiotics in treating uncomplicated URIs in the EDs remains prevalent. Furthermore, overutilization of imaging studies is prevalent. Changes at levels of health care system and hospitals are needed to avoid unnecessary resource utilization. In addition, further patient education about antibiotic use in the community may greatly facilitate the transition out of an antibiotic-dependent consumer culture.

Assembly and characterization of pandemic influenza A H1N1 genome in nasopharyngeal swabs using high-throughput pyrosequencing.

De novo high-throughput pyrosequencing was used to detect and characterize 2009 pandemic influenza A (H1N1) virus directly in nasopharyngeal swabs in the context of the microbial community. Data were generated with a prior sequence independent amplification by 454 pyrosequencing on GS-FLX platform (Roche). Influenza A assembled reads allowed near full-length genome reconstruction with the simultaneous analysis of site-specific heterogeneity. The molecular approach applied proved to be a powerful tool to characterize the new pandemic H1N1 influenza virus in clinical samples. This approach could be of great value in identifying possibly new reassortants that may occur in the near future.

Pediatric allergic rhinitis and comorbid disorders.

Allergic rhinitis (AR) is rarely found in isolation and needs to be considered in the context of systemic allergic disease associated with numerous comorbid disorders, including asthma, chronic middle ear effusions, sinusitis, lymphoid hypertrophy with obstructive sleep apnea, disordered sleep, and consequent behavioral and educational effects. The coexistence of AR and asthma is complex. First, the diagnosis of asthma may be confounded by symptoms of cough caused by rhinitis and postnasal drip. This may lead to either inaccurate diagnosis of asthma or inappropriate assessment of asthma severity with over treatment of the patient. The term "cough variant rhinitis" is therefore proposed to describe rhinitis that manifests itself primarily as cough that results from postnasal drip. AR, however, also has a causal role in asthma; it appears both to be responsible for exacerbating asthma and to have a role in its pathogenesis. Postnasal drip with nasopharyngeal inflammation leads to a number of other conditions. Thus sinusitis is a frequent extension of rhinitis and is one of the most frequently missed diagnoses in children. Allergen exposure in the nasopharynx with release of histamine and other mediators can cause Eustachian tube obstruction possibly leading to middle ear effusions. Chronic allergic inflammation of the upper airway causes lymphoid hypertrophy with prominence of adenoidal and tonsillar tissue. This may be associated with poor appetite, poor growth, and obstructive sleep apnea. AR is therefore part of a spectrum of allergic disorders that can profoundly affect the well being and quality of life of a child. Prospective cohort studies are required to assess the disease burden caused by AR in childhood and to further assess the potential educational impairment that may result. Because AR is part of a systemic disease process, its management requires a coordinated approach rather than a fragmented, organ-based approach.

[Tuberculosis of the mucosa of the naso-pharynx. A clinical study of 37 cases seen at the Gustave-Roussy Institute between 1961 and 1978 (author's transl)]. / La tuberculose des muqueuses des V.A.D.S. Etude clinique à propos de 37 cas suivis à l'I.G.R.

The authors report a series of 37 cases presenting with tuberculosis of the mucosa of the upper naso-pharynx. The localization broke down as: 5 cases of tuberculosis of naso-sinuses, 6 of the buccal cavity, 3 of the cavum, 10 of the oro-pharynx, 1 of the hypopharynx, and 12 of the larynx. -- The male-female ratio was unequal (2:1 M:F) -- The mean age was 52.5 years -- Most patients were European. The 3 rhinopharyngeal cases were in North Africans. -- Macroscopically the lesions were of a malignant character in 70%. -- There was palpable lymphadenopathy in 56% of patients. The most commonly involved chain was the jugulo-carotid, especially the subdigastric group. -- There was tuberculosis in the entourage in 20/37 cases. CXR was normal in 17 cases. On hospitalisation active T.b. was discovered in 15 cases. -- Biopsy confirmed a definitive diagnosis in every case. -- All patients were treated medically. There were no cases of resistant organisms. The results were excellent.