Patients received a single dose of vaccine (0.5ml) subcutaneously from October 2011 until January 2012. patients receiving TCZ therapy with or without MTX. Keywords:Infections, Rheumatoid Arthritis, Vaccination == Introduction == Influenza vaccination is the most effective method for preventing influenza virus infection and its potentially severe complications. Patients with rheumatoid arthritis (RA) are at an increased risk for infectious diseases due to TGR-1202 the nature of RA and its treatment with immunosuppressive agents;1therefore, this patient population is a potential candidate for influenza vaccination. Treatment with antitumour necrosis factor (anti-TNF) agents may impair antibody response to influenza vaccination in patients with RA and other rheumatic diseases, but the Rabbit Polyclonal to STA13 response is large enough to warrant influenza vaccination for TGR-1202 such patients.28 Tocilizumab (TCZ), a humanised monoclonal interleukin-6 (IL-6) receptor antibody, is effective in the treatment of patients with moderate to severe RA who have shown inadequate responses to methotrexate (MTX) and one or more anti-TNF agents.9Our concern is the impact of TCZ on protective antibody response to influenza vaccination because IL-6 was originally identified as a factor that plays an essential role in terminal differentiation of B cells into antibody producing plasma cells.10Data regarding the efficacy and safety of influenza vaccination are lacking in RA patients receiving TCZ. Only one attempt at evaluating the efficacy of influenza vaccine has so far been made in a small number of paediatric patients receiving TCZ therapy for systemic onset juvenile idiopathic arthritis.11 To address this issue, we determined antibody response to trivalent inactivated influenza vaccine in RA patients being treated with TCZ, MTX or both agents, and compared parameters for efficacy of vaccination among these groups. == Methods == == Patients == RA patients aged 18 or older who had been receiving TCZ (an intravenous infusion of 8 mg/kg every 4 weeks) for at least 4 weeks and/or MTX (618 mg per week) for 12 weeks or more at our rheumatology outpatient clinics were invited to participate in this open-label study. RA patients who had been receiving bucillamine or salazosulphapyridine were also included as RA controls. All participants fulfilled the 1987 American College of Rheumatology criteria for diagnosis of RA. Exclusion criteria were current use of 10 mg/day or more of prednisolone, current use of tacrolimus or leflunomide, a recent history (within 3 months) of influenza infection, and a recent history (within 6 months) of influenza vaccination. == Vaccine == We used commercially available inactivated trivalent influenza vaccine (Biken HA, Mitsubishi Tanabe Pharm Corporation, Osaka, Japan) containing 30 g of purified haemagglutinin of each of the following: A/California/7/2009 (H1N1)-like strain (A/H1N1 strain), A/Victoria/210/2009 (H3N2)-like strain (A/H3N2 strain) and B/Brisbane/60/2008-like strain (B/B1 strain). Patients received a single dose of vaccine (0.5 ml) subcutaneously from October 2011 until January 2012. For RA patients receiving TCZ, the vaccination was done on the same day as TCZ infusion. == HI tests == Sera were collected immediately before and 46 weeks after vaccination. For the detection of influenza antibodies, haemagglutination inhibition (HI) tests were performed in duplicate at SRL (Tachikawa, Tokyo, Japan), according to WHO standard procedure using haemagglutinin antigens representing all three strains TGR-1202 that were included in the vaccine. Geometric mean titres (GMTs) of HI antibodies before and after vaccination, and fold increases relative to prevaccination titres (geometric means of postvaccination to prevaccination antibody titre ratios) were determined. GMTs were calculated from log-transformed values of HI antibody titres. For statistical analysis, a titre of 5 was arbitrarily assigned to sera with undetectable titres of <10. Seroprotection was defined as antibody titres of 40. Seroconversion was defined as postvaccination antibody titres of 40 in patients whose prevaccination titres were <10. Seroresponse was defined as seroconversion or fold increases in antibody.