Analysis of C-reactive protein levels and febrile tendency after joint surgery in rheumatoid arthritis patients treated with a perioperative 4-week interruption of tocilizumab

Abstract

Tocilizumab is a humanized anti-human IL-6 receptor monoclonal antibody that has been demonstrated to improve rheumatoid arthritis (RA) symptoms [1–5]. However, it remains unclear whether the use of biological agents, including tocilizumab, constitutes an independent risk factor for postoperative surgical site infection (SSI). Some reports of joint surgeries in RA patients treated with tumor necrosis factor (TNF) alpha blockers have demonstrated no increase in the incidence of postoperative infection [6, 7]. In contrast, other reports have suggested higher complication rates with TNF blockers [8, 9]. We also reported that the use of TNF blockers was a likely cause of SSI [10], although we diagnosed SSI using the criteria for defining SSI in the Guideline for Prevention of Surgical Site Infection, 1999 [11]. These conflicting data make the effects of TNF blocker therapy on the risk of postoperative infection during orthopedic intervention unclear. Meanwhile, the perioperative mechanisms of tocilizumab are also currently under investigation. Unfortunately, only one study of the clinical features of tocilizumab-treated RA patients following joint surgery has been published [12]. Therefore, more data are required to fully evaluate the influence of tocilizumab on postoperative complications. We analyzed clinical features after 8 joint surgeries in 5 patients treated with tocilizumab (TCZ group) at our institute from October 2007 to September 2009. Moreover, as a retrospective 1:2 matched case–control study, 16 joint surgeries in anti-TNF-treated RA patients (TNF group) and 16 joint surgeries in patients treated with conventional disease-modifying antirheumatic drugs (DMARDs group), matched for type of surgery and gender, were compared to the TCZ group in order to evaluate laboratory data and body temperature changes during the 2 weeks following surgery (see Table 1 for the baseline characteristics of each study population). TCZ group surgeries included wrist arthroplasty (n = 2); unilateral, total hip arthroplasty (THA) (n = 3); unilateral, total knee arthroplasty (TKA) (n = 1); unilateral, total elbow arthroplasty (n = 1); and foot surgery (n = 1). The surgeries on patients treated with TNF blockers were performed in accordance with the British Society for Rheumatology and the Japan College of Rheumatology guidelines [13, 14]. Tocilizumab treatment was withheld for 4 weeks prior to surgery, and was restarted 4 weeks after surgery. Preoperative CRP levels in the TCZ group were within the normal range in all cases, except for one case with CRP 0.44 mg/dl. The average CRP levels in the TNF and DMARDs groups exceeded 8 mg/dl on postoperative day 2, while the average level in the TCZ group increased to only *2 mg/dl (TCZ vs. TNF blockers, P = 0.025 by Mann–Whitney U test) (Fig. 1). Additionally, patients in the TNF and DMARDs groups tended to become febrile; while the average body temperature also increased in the TCZ group, it never reached 37 C (Fig. 1). No differences in WBC count, hemoglobin level, or platelet count were R. Hiroshima K. Kawakami T. Iwamoto A. Tokita K. Yano Y. Sakuma K. Ikari S. Momohara (&) Department of Orthopaedic Surgery, Institute of Rheumatology, Tokyo Women’s Medical University, 10-22 Kawada, Shinjuku, Tokyo 162-0054, Japan e-mail: smomohara@ior.twmu.ac.jp