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(401) Mast cell stabilizer (ketotifen): implications for the pathophysiology of Fibromyalgia

      Emerging data suggest that fibromyalgia (FM) is a neuro-immunologic disorder. Compared to healthy controls, FM patients have greater number of skin mast cells - potent inflammatory cells capable of releasing pro-inflammatory and neuro-sensitisizing molecules. Whether or not these cells are involved in the pathogenesis of FM is unclear. We designed a randomized controlled trial to determine the effects of a mast cell stabilizer (ketotifen) on FM symptoms. Ketotifen is commonly used to treat two mast cell-mediated conditions, bronchial asthma and allergic skin disorders. Fifty-one FM subjects were randomized to daily oral ketotifen 2 mg BID (n=24) for 8 weeks or placebo (N=27). Those with atopic dermatitis, chronic urticaria, or taking anti-allergy drugs were excluded. Demographics of the 51 FM subjects: mean age= 51.2 (SD 8.4) years; female=88%; whites= 88%; ≥high school graduates=71%; concomitant opiates=22%; PHQ-8 depression=13.5 (5.4); experimental pressure pain sensitivity (range 0-20) = 10.0 (0.4); weekly average pain intensity (ActiWatch Pain Monitor) = 6.4 (1.1); and revised FIQ (global FM symptom severity) =66.8 (14.0). We found no statistically significant treatment group differences in the baseline to week 8 changes of our two primary measures: weekly average pain intensity [ketotifen -1.3 (1.9) vs. placebo -1.5 (1.9), p=0.7]; and revised FIQ [-12.1 (19.5) vs. -12.2 (18.1), p=0.9]. Further, no secondary outcome measures (BPI pain intensity, and experimental pressure pain sensitivity) reached statistical significance (p>0.5). Our results did not differ in the intent-to-treat and completer analyses. Three subjects in the ketotifen group and 2 in the placebo group discontinued the study due to study protocol violations. Other than transient sedation [6 (28.6%) vs. 1 (4.0%)], oral ketotifen was well tolerated. In conclusion, oral ketotifen was not associated with improvement of FM symptoms. Importantly, skin mast cells are not major contributor in the pathogenesis of FM. Funded by NIAMS (NIH).