Pregabalin in fibromyalgia - responder analysis from individual patient data

<p>Abstract</p> <p>Background</p> <p>Population mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores.</p> <p>Methods</p> <p>We obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (≥ 0%), minimal improvement (≥ 15%), moderate improvement (≥ 30%), substantial improvement (≥ 50%), and extensive improvement (≥ 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo.</p> <p>Results</p> <p>Information from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs (with 95% confidence intervals) for ≥ 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for ≥ 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response.</p> <p>Conclusions</p> <p>Responder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects.</p

Pregabalin, celecoxib, and their combination for treatment of chronic low-back pain

Background - The efficacy and safety of the association of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] and pregabalin (commonly used to control neuropathic pain), compared with monotherapy of each, were evaluated for the treatment of chronic low-back pain, a condition known to be due to neuropathic as well as nociceptive pain mechanisms. Materials and methods - In this prospective randomized trial, 36 patients received three consecutive 4-week treatment regimes, randomly assigned: celecoxib plus placebo, pregabalin plus placebo, and celecoxib plus pregabalin. All patients were assessed by using a visual analogue scale (VAS, 0\u2013100 mm) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale by an investigator blinded to the administered pharmacological treatment. Results - Celecoxib and pregabalin were effective in reducing low-back pain when patients were pooled according to LANSS score. The association of celecoxib and pregabalin was more effective than either monotherapy in a mixed population of patients with chronic low-back pain and when data were pooled according to LANSS score. Adverse effects of drug association and monotherapies were similar, with reduced drug consumption in the combined therapy. Conclusions - Combination of celecoxib and pregabalin is more effective than monotherapy for chronic low-back pain, with similar adverse effects

Interference with work in fibromyalgia - effect of treatment with pregabalin and relation to pain response

BACKGROUND: Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately. METHODS: We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group (pregabalin 150-600 mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100 mm visual analogue pain scale [VAS]). RESULTS: Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p &lt; 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p &lt; 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p &lt; 0.0001) for those experiencing &gt;/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p &lt; 0.0001) for those achieving a low level of pain at trial end (&lt;30 mm on the VAS). Patients achieving both &gt;/= 50% pain improvement and a pain score &lt;30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p &lt; 0.0001). Analysing answers to the other questions yielded qualitatively similar results. CONCLUSIONS: Effective pain treatment goes along with benefit regarding work. A reduction in time off work &gt;1 day per week can be achieved in patients with good pain responses

The role of dendritic cells in the immunopathogenesis of psoriasis

Psoriasis vulgaris is a chronic inflammatory skin disease that is marked by a complex interplay of dendritic cells (DCs), T-cells, cytokines, and downstream transcription factors as part of a self-sustaining type 1 cytokine network. As integral players of the immune system, DCs represent antigen-presenting cells that are crucial for efficient activation of T-cells and B-cells. DCs have also been linked to distinct chronic inflammatory conditions, including psoriasis. In the setting of psoriasis therapy, DC/T cell interactions serve as a potential target for biologic response modifiers. Here we describe the major DC subsets as well as the immunologic involvement of DCs within the context of psoriatic lesions

Home Telehealth Uptake and Continued Use Among Heart Failure and Chronic Obstructive Pulmonary Disease Patients: a Systematic Review

Background Home telehealth has the potential to benefit heart failure (HF) and chronic obstructive pulmonary disease (COPD) patients, however large-scale deployment is yet to be achieved. Purpose The aim of this review was to assess levels of uptake of home telehealth by patients with HF and COPD and the factors that determine whether patients do or do not accept and continue to use telehealth. Methods This research performs a narrative synthesis of the results from included studies. Results Thirty-seven studies met the inclusion criteria. Studies that reported rates of refusal and/or withdrawal found that almost one third of patients who were offered telehealth refused and one fifth of participants who did accept later abandoned telehealth. Seven barriers to, and nine facilitators of, home telehealth use were identified. Conclusions Research reports need to provide more details regarding telehealth refusal and abandonment, in order to understand the reasons why patients decide not to use telehealth

Hidden dynamics of soccer leagues: the predictive ‘power’ of partial standings

Objectives Soccer leagues reflect the partial standings of the teams involved after each round of competition. However, the ability of partial league standings to predict end-of-season position has largely been ignored. Here we analyze historical partial standings from English soccer to understand the mathematics underpinning league performance and evaluate the predictive ‘power’ of partial standings. Methods Match data (1995-2017) from the four senior English leagues was analyzed, together with random match scores generated for hypothetical leagues of equivalent size. For each season the partial standings were computed and Kendall’s normalized tau-distance and Spearman r-values determined. Best-fit power-law and logarithmic functions were applied to the respective tau-distance and Spearman curves, with the ‘goodness-of-fit’ assessed using the R2 value. The predictive ability of the partial standings was evaluated by computing the transition probabilities between the standings at rounds 10, 20 and 30 and the final end-of-season standings for the 22 seasons. The impact of reordering match fixtures was also evaluated. Results All four English leagues behaved similarly, irrespective of the teams involved, with the tau-distance conforming closely to a power law (R2>0.80) and the Spearman r-value obeying a logarithmic function (R2>0.87). The randomized leagues also conformed to a power-law, but had a different shape. In the English leagues, team position relative to end-of-season standing became ‘fixed’ much earlier in the season than was the case with the randomized leagues. In the Premier League, 76.9% of the variance in the final standings was explained by round-10, 87.0% by round-20, and 93.9% by round-30. Reordering of match fixtures appeared to alter the shape of the tau-distance curves. Conclusions All soccer leagues appear to conform to mathematical laws, which constrain the league standings as the season progresses. This means that partial standings can be used to predict end-of-season league position with reasonable accuracy