Effectiveness and safety of dolutegravir two-drug regimens in virologically suppressed people living with HIV: a systematic literature review and meta-analysis of real-world evidence.

OBJECTIVES: Dolutegravir (DTG) is widely recommended within three-drug regimens. However, similar efficacy and tolerability have also been achieved with DTG within two-drug regimens in clinical trials. This study evaluated the real-world effectiveness and discontinuations in people living with HIV-1 (PLHIV) switching to DTG with lamivudine (3TC) or rilpivirine (RPV). METHODS: This was a one-arm meta-analysis utilizing data from a systematic literature review. Data from real-world evidence studies of DTG + RPV and DTG + 3TC were extracted, pooled and analysed. The primary outcome was the proportion of patients with viral failure (VF; ≥ 50 copies/mL in two consecutive measurements and/or ≥ 1000 copies/mL in a single measurement) at week 48 (W48) and week 96 (W96). Other outcomes included virological suppression (VS; < 50 copies/mL) and discontinuations (W48 and W96). Estimates were calculated for VF, VS as per snapshot (VSS) and on treatment analysis (VSOT), and discontinuations. RESULTS: Pooled mean estimates of VF for DTG + 3TC and DTG + RPV were 0.8% [95% confidence interval (CI): 0.4-1.3] and 0.6% (95% CI: 0.0-1.6), respectively, at W48. VSS rate at W48 was 85.0% (95% CI: 82.3-87.5) for DTG + 3TC regimen and 92.4% (95% CI: 85.0-97.7) in the DTG + RPV regimen. The DTG + 3TC and DTG + RPV regimens led to discontinuations in 13.6% (95% CI: 11.1-16.2) and 7.2% (95% CI: 2.1-14.4) of patients, respectively, at W48. Similar results were observed at W96. CONCLUSIONS: Treatment with DTG + 3TC or DTG + RPV in clinical practice provides a low rate of VF and a high rate of VS when initiated in virologically suppressed PLHIV with diverse backgrounds.

Prevalence and burden of dyspnoea among COPD patients in Japan.

BACKGROUND AND AIMS: Dyspnoea is the most common symptom of chronic obstructive pulmonary disease (COPD) significantly affecting activity, impairing patients' well-being and contributing to the economic burden of COPD. The objective of this study was to estimate the prevalence of dyspnoea and its impact on COPD management costs in Japan. METHODS: A cross-sectional survey was conducted among 82 internal medicine physicians and 85 respiratory specialists representing 420 patients with COPD in Japan. Information was collected on demographic and clinical characteristics, dyspnoea (mMRC scale), and healthcare resource use. Dyspnoea prevalence was estimated among all patients and those on specific COPD treatments. The economic burden was derived from two cohorts based on their level of dyspnoea that were matched by propensity scores balancing their demographic and disease burden characteristics. RESULTS: Moderate-severe dyspnoea (mMRC score ≥ 2) was reported by 37.5% of COPD patients and ranging from 21.5% among patients treated with a mono bronchodilator to 59.8% among patients treated with triple therapy. Descriptive analysis showed that dyspnoeic patients have higher annual costs attributable to consultations (€2999 vs. €1906), medications (€1139 vs. €716), exacerbations (€674 vs. €36), other resources (€1789 vs. €140) and in total (€6348 vs. €2797) (p < 0.0001 for all comparisons) compared to patients with mild or no dyspnoea (mMRC score < 2). The total costs remained significantly higher in a propensity-matched cohort adjusted for severity and cardiovascular comorbidity [€6776.1 vs. €4461.3, p = 0.0236]. CONCLUSION: Moderate-severe dyspnoea is common among consulting COPD patients in Japan and is a significant cost driver for the healthcare system.

Estimating the effect of nasal steroid treatment on repeat polypectomies: survival time analysis using the General Practice Research Database.

BACKGROUND: Intranasal steroids are effective in preventing or delaying recurrence of nasal polyps. However, their effectiveness in delaying a need for repeat polypectomy in clinical practice is unknown. OBJECTIVES: To compare time to a repeat polypectomy between post-polypectomy intranasal steroid users and non-users. METHODOLOGY/PRINCIPLE: Our cohort consisted of patients in GPRD who had undergone at least one nasal polypectomy procedure in or after the year 2000. These patients were followed for up to 4 years and the time to next polypectomy was estimated. Cox`s proportional hazards regression was used to estimate the effect of post polypectomy intranasal steroid treatment on time to the next polypectomy after controlling for other respiratory conditions and their treatment. RESULTS: The cohort consisted of 1,675 patients with a mean age of 59 years and 68% males. Of these, 576 patients were post-polypectomy steroid users and 1,099 patients were steroid non-users. The median time to repeat polypectomy was 812 days among the steroid users and 736 days among steroid non-users. Significantly less proportion of intranasal steroid users experienced a repeat polypectomy compared to steroid non-users. This difference was consistent among subgroups of females and concomitant rhinitis treatments users. Patients with post polypectomy intranasal steroid use showed lower risk for a repeat polypectomy compared to steroid non-users. Concomitant rhinitis medication users showed a higher risk whereas other confounders were not significant. CONCLUSIONS: Intranasal steroids were effective in delaying a repeat polypectomy. However, further research using a prospective design is necessary to quantify the benefit of ongoing steroid treatment.

Establishing the sequential progression of multiple allergic diagnoses in a UK birth cohort using the General Practice Research Database.

BACKGROUND: There is considerable international interest in understanding the sequential progression of multiple allergic conditions (also sometimes known as 'the allergic march'). OBJECTIVES: To study the sequential progression of multiple allergic conditions in a national birth cohort throughout childhood. METHODS: We constructed a birth cohort of 43,477 children born in 1990 and registered in UK general practices within a year of birth, using the national General Practice Research Database. Of these, 24,112 with complete follow-up until the age of 18 years were studied in order to understand disease progression and to estimate the absolute and relative risks of developing second and third allergic diagnoses following an index allergic condition. RESULTS: 52.1% of children were diagnosed with at least one condition at some point in childhood. We were able to describe 15 different disease trajectories. Eczema was the most likely index condition with 60.7% [95% confidence interval (CI): 59.8-61.6] of allergy sufferers being diagnosed with this condition first. For those with a diagnosis of eczema, the relative risks of being diagnosed with asthma followed by rhinitis and rhinitis followed by asthma were 1.59 (95% CI: 1.32-1.91; P<0.0001) and 0.54 (95% CI: 0.43-0.68; P<0.0001), respectively. For those diagnosed with asthma first, the relative risks of being diagnosed with eczema followed by rhinitis and rhinitis followed by eczema were 1.27 (95% CI: 0.96-1.68; P=0.095) and 0.27 (95% CI: 0.20-0.36; P<0.0001), respectively. For those diagnosed with rhinitis first, the relative risks of being diagnosed with eczema followed by asthma and asthma followed by eczema were 0.64 (95% CI: 0.42-0.95; P=0.025) and 0.47 (95% CI: 0.32-0.67; P<0.0001), respectively. CONCLUSIONS: Among children diagnosed with multiple allergic diseases there is likely to be a number of variants of 'the allergic march'. Of these, the diagnosis of eczema followed by asthma, which is in turn followed by rhinitis, is the most common trajectory. Surprisingly, some diagnoses indicate a possible strong protective effect of manifesting further likely allergic diagnoses.

Establishing the incidence and prevalence of clinician-diagnosed allergic conditions in children and adolescents using routinely collected data from general practices.

BACKGROUND: There remains a need to better characterize the epidemiology of allergic disorders, particularly in relation to describing the incidence, natural history and co-morbidity of allergic conditions. OBJECTIVES: To estimate the incidence and prevalence of clinician-diagnosed eczema, asthma and rhinitis, alone and in combination, in children and adolescents in the United Kingdom. METHODS: Using the national General Practice Research Database (GPRD) - one of the largest validated databases of routinely collected healthcare data in the world aggregating 3.6 million individuals - we constructed a retrospective birth cohort of 43,473 children born in the year 1990 and registered with a UK general practice within a year of birth. The cohort was followed until 2008 or the longest available follow-up period to determine the cumulative and age-specific incidence and prevalence rates of clinician-diagnosed eczema, asthma and rhinitis, and an 18-year prevalence of these conditions, alone and in combination. RESULTS: Eczema had the highest incidence density of 226.9 per 10,000 person-years [95% confidence interval (CI): 225.8-228.0] followed by asthma [136.6;(95% CI: 135.7-137.5)] and rhinitis [61.4;(95% CI: 60.8-62.0)], by the age of 18 years. The incidence densities of suffering from one, two or all three allergic conditions were 323.2 (95% CI: 322.0-324.4), 206.4 (95% CI: 205.7-207.1) and 141.9 (95% CI: 141.4-142.4) per 10,000 person-years, respectively. Among the 24 112 children with a complete 18-year follow-up, eczema had the highest 18-year prevalence of clinician-diagnosed condition at 36.5% (95% CI: 35.9-37.2%) followed by asthma [22.9;(95% CI: 22.3-23.4%)] and rhinitis[11.4;(95% CI: 11.0-11.8%)]. The 18-year prevalence of more than one and all three conditions was 16.1% (95% CI: 15.6-16.6%) and 2.5% (95% CI: 2.4-2.8%), respectively. CONCLUSIONS: This is one of the first studies to provide national estimates on the age-specific incidence and age-specific prevalence of the major allergic disorders showing clinician-diagnosed eczema, asthma and rhinitis to have high incidence rates in early childhood. A significant proportion of children experience and are diagnosed with multiple allergic conditions in early childhood.

A model of the long-term cost effectiveness of scheduled maintenance treatment with infliximab for moderate-to-severe ulcerative colitis.

BACKGROUND: Infliximab (IFX) has been shown to be efficacious in moderate-severe ulcerative colitis (UC). Aim To evaluate the cost-effectiveness of a scheduled maintenance treatment (SMT) with IFX in moderate-severe UC patients. METHODS: A Markov model was constructed to simulate the progression of a cohort of moderate-severe UC patients treated with IFX (5 mg/kg) SMT. Transitions were estimated from two phase III trials of IFX (ACT I and ACT II). Standard care, comprising immunomodulators and/or corticosteroids was used as a comparator. Two separate treatment strategies were evaluated - continued treatment in IFX responders and continued treatment in IFX patients achieving remission. The dose of IFX was estimated for a 73 kg typical UC patient in the UK. The results were calculated over 10 years using a discount rate of 3.5% for costs and outcomes. The outcome measure was quality-adjusted life years (QALYs) estimated using EQ-5D. Sensitivity analyses explored the uncertainty around the results. RESULTS: The incremental cost effectiveness ratio (ICER) for IFX was 27,424 pounds in the responder strategy and 19,696 pounds in the remission strategy at 10 years. In sensitivity analysis, the ICER for IFX in the responder strategy ranged from 21,066 pounds to 86,322 pounds and in the remission strategy ranged from 14,728 pounds to 46,765 pounds. The model time horizon and patient body weight were important factors affecting results. CONCLUSION: Eight-week SMT with IFX appears to be a cost-effective treatment option for adult patients suffering from moderate to severe UC.

Health-economic analysis: cost-effectiveness of scheduled maintenance treatment with infliximab for Crohn's disease--modelling outcomes in active luminal and fistulizing disease in adults.

BACKGROUND: Infliximab has been shown to be efficacious in moderate-to-severe Crohn's disease (CD). AIM: To evaluate the cost-effectiveness of scheduled maintenance treatment with infliximab in luminal and fistulizing CD patients. METHODS: Markov models were constructed to simulate the progression of adult CD patients with and without fistulae during treatment with infliximab (5 mg/kg). Transitions were estimated from published clinical trials of infliximab. Standard care, comprising immunomodulators and/or corticosteroids was used as a comparator. An average weight of 60 kg was used to estimate the dose of infliximab. The costs and outcomes were discounted at 3.5% over 5 years. The primary effectiveness measurement was quality-adjusted life years (QALYs) estimated using EQ-5D. One-way and probabilistic sensitivity analyses were performed by varying the infliximab efficacy estimates, costs and utilities. RESULTS: The incremental cost per QALY gained was pound 26,128 in luminal CD and pound 29,752 in fistulizing CD at 5 years. Results were robust and remained in the range of pound 23,752- pound 38,848 for luminal CD and pound 27,047- pound 44,206 for fistulizing CD. Patient body weight was the most important factor affecting cost-effectiveness. CONCLUSION: Eight-week scheduled maintenance treatment with infliximab is a cost-effective treatment for adult patients suffering from active luminal or fistulizing CD.