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

Cigarette smoking and the risk of primary Sjögren's syndrome : A nested case control study

Background: Smoking is reported to affect the risk of a number of chronic disorders, including rheumatic diseases. Previous cross-sectional studies have shown a lower frequency of smoking in patients with primary Sjögren's syndrome (pSS). The aim of this study was to investigate the impact of smoking and socioeconomic status on the risk of subsequent diagnosis of pSS in a nested case-control study. Method: Participants in two large population-based health surveys who were later diagnosed with pSS were identified through linkage with the Malmö Sjögren's Syndrome Register. Matched controls were obtained from the health surveys. Results: Sixty-three patients with pSS with pre-diagnostic data from the health surveys were identified. Current smoking was associated with a significantly lower risk of later being diagnosed with pSS (odds ratio (OR) 0.3; 95% CI 0.1-0.6). Furthermore, former smoking was associated with an increased risk of subsequent pSS diagnosis (OR 4.0; 95% CI 1.8-8.8) compared to never smoking. Similar results were found in a sub-analysis of patients with reported symptom onset after inclusion in the health surveys. Socioeconomic status and levels of formal education had no significant impact on the risk of later being diagnosed with pSS. Conclusion: In this nested case-control study, current smoking was associated with a reduced risk of subsequent diagnosis of pSS. In addition, former smoking was associated with an increased risk. Whether this reflects a biological effect of cigarette smoking or other mechanisms should be further investigated in future studies