The Effectiveness of Treatments for Patients With Medication Overuse Headache: A Systematic Review and Meta-Analysis

© 2016 American Pain Society Worldwide, approximately 1 to 2% of the adult population suffers from chronic headache due to overuse of pain medication. Guidelines recommend acute withdrawal of medication, but the optimal treatment remains unknown. We aimed to evaluate the benefit of treatments for patients with medication overuse headache (MOH). We performed an extensive literature search until November 2015, selecting randomized controlled trials that evaluated interventions for adults with MOH. Two authors assessed the eligible trials and extracted data. We calculated effect estimates and used the random effects model for the pooled analysis. Our primary outcome measures were ‘headache days’ and ‘days with medication.’ Outcome data were categorized as short-term (up to 12 weeks) or long-term (≥12 weeks) outcomes. This review consists of 16 trials including 1,105 patients. Four trials evaluated the use of prednisone with placebo or celecoxib after medication withdrawal; 7 trials evaluated various methods of withdrawal versus other methods of withdrawal, and 5 trials evaluated prophylactic medication compared with placebo or ibuprofen. We found no significant differences in headache days between prednisone versus placebo or between outpatient versus inpatient treatment, but we found a significant difference in days with medication. Overall, we found no benefit of prophylactic medication versus placebo. We found low to very low quality of evidence of no benefit of prednisone, prophylaxis, and various withdrawal interventions. Because the burden of MOH for patients is enormous, larger and high-quality intervention trials are needed. Perspective This article presents a critical look at studies of patients with MOHs. It appears that the withdrawal strategy remains the best treatment option, although there is scant evidence on the efficacy of any treatment options

Patients with Inflammatory Bowel Disease Show IgG Immune Responses Towards Specific Intestinal Bacterial Genera

Introduction: Inflammatory bowel disease (IBD) is characterized by a disturbed gut microbiota composition. Patients with IBD have both elevated mucosal and serum levels of IgG-antibodies directed against bacterial antigens, including flagellins. In this study, we aimed to determine to which intestinal bacteria the humoral immune response is directed to in patients with IBD. Methods: Fecal and serum samples were collected from patients with IBD (n=55) and age- and sex-matched healthy controls (n=55). Fecal samples were incubated with autologous serum and IgG-coated fractions were isolated by magnetic-activated cell sorting (MACS) and its efficiency was assessed by flow cytometry. The bacterial composition of both untreated and IgG-coated fecal samples was determined by 16S rRNA-gene Illumina sequencing. Results: IgG-coated fecal samples were characterized by significantly lower microbial diversity compared to the fecal microbiome. Both in patients with IBD and controls, serum IgG responses were primarily directed to Streptococcus, Lactobacillus, Lactococcus, Enterococcus, Veillonella and Enterobacteriaceae, as well as against specific Lachnospiraceae bacteria, including Coprococcus and Dorea (all P<0.001), and to Ruminococcus gnavus-like bacteria (P<0.05). In contrast, serological IgG responses against typical commensal, anaerobic and colonic microbial species were rather low, e.g. to the Lachnospiraceae members Roseburia and Blautia, to Faecalibacterium, as well as to Bacteroides. Patients with IBD showed more IgG-coating of Streptococcus, Lactobacillus, and Lactococcus bacteria compared to healthy controls (all P<0.05). No differences in IgG-coated bacterial fractions were observed between Crohn’s disease and ulcerative colitis, between active or non-active disease, nor between different disease locations. Conclusion: The IgG immune response is specifically targeted at distinct intestinal bacterial genera that are typically associated with the small intestinal microbiota, whereas responses against more colonic-type commensals are lower, which was particularly the case for patients with IBD. These findings may be indicative of a strong immunological exposure to potentially pathogenic intestinal bacteria in concordance with relative immune tolerance against commensal bacteria