Interferon-likre Flu like symptoms aren't mediated by Histamine

Landi D, Albanese M, Buttari F, Monteleone F, Boffa L, Rossi S, Motta C, Puma E, Centonze D.Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study.
PLoS One. 2017 Jul 7;12(7):e0165415

BACKGROUND: Flu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis(RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS.
METHODS:We conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1) 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2) first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)] after 4 weeks of treatment within each sequence.
RESULTS: Forty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference -0.15; 95% confidence interval: from -0.74 to 0.44; p = 0.6029). The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile.
CONCLUSIONS:The addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFNβ-induced FLS.

Systemic post-injection reactions, often termed flu-like symptoms , occur in approximately half of all people treated with IFNβs and can affect adherence to therapy. These symptoms, which include pyrexia (fever), chills, malaise (discomfort), myalgia (muscle aches), and headaches, usually resolve within 24 hours or persist intermittently following each injection. I don't need to say much except that this approach did not work

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