Rheumatoid factor appearance after tocilizumab treatment seems to predict bad therapeutical response in rheumatoid arthritis

Abstract

Reduction of rheumatoid factor (RF) serum levels have been described during anti-TNF treatment in patients with rheumatoid arthritis (RA) [1]. Some studies have shown a relationship between this RF alterations and the clinical response [2]. However, no description on RF fluctuation has been reported with tocilizumab. Only one article defined that remission after tocilizumab is superior in patients with higher titers of IgM RF [3]. From 21 patients with RA, 9 were excluded due to previously positive RF before tocilizumab use. The other 12 patients had their record extensively examined, and we found only two patients who evolved with positive RF, the remaining 10 patients continued negative for this antibody. We herein describe two patients with rheumatoid arthritis who had rheumatoid factor production after tocilizumab use and bad response to this treatment. The first case was a 28-year-old female diagnosed in 2008 as seronegative rheumatoid arthritis and received non-steroidal anti-inflammatory drugs (NSAID), prednisone, methotrexate (up to 15 mg/week), hydroxichloroquine, leflunomide (20 mg/day) and abatacept. When she continued to show evidence of disease activity while receiving MTX and prednisone, tocilizumab was then indicated. After tocilizumab (620 mg monthly), she experienced initial improvement of clinical picture; however, after 2 months, the RA had flares and continued to be refractory, with C-reactive protein of 12 mg/L [normal value (NV): \6 mg/L], erythrocyte sedimentation rate (ESR) of 25 mm/1st hours (NV: \20 mm/1st hour) and alpha-1-glycoprotein I of 57.9 mg/dL (NV: 41-121 mg/dL). After 6 doses of tocilizumab, her rheumatoid factor detection was positive with titer of 654 IU/mL (NV: \8 IU/mL). The second case was a 59-year-old woman with previous history of diabetes and systemic hypertension. Seronegative rheumatoid arthritis was diagnosed in 2005. She was treated with NSAID, leflunomide (20 mg/day), sulphasalazine (2 g/day) and hydroxichloroquine (400 mg/day). Tocilizumab was indicated in October 2010, when she was refractory to these previous drugs. After 5 months of tocilizumab (560 mg monthly), she continued to experience clinical and laboratory disease activity, with C-reactive protein of 6.2 mg/L (NV: \6 mg/L), erythrocyte sedimentation rate (ESR) of 27 mm/1st hours (NV: \20 mm/1st hour) and alpha-1-glycoprotein I of 129 mg/dL (NV: 41–121 mg/ dL), and her rheumatoid factor detection was positive with 473 IU/mL (NV: \20 IU/mL). Autoantibodies production after biological therapy has been described and rarely is associated with disease onset [4]. In this line, more than 60% of rheumatoid arthritis patients treated with infliximab develop antinuclear antibodies [5]. Patients with Crohn’s disease may also have these autoantibodies [6]. Our group demonstrated that half of the patients with psoriatic arthritis may develop autoantibodies during anti-TNF treatment [7]. On the other hand, other studies have shown decreasing of rheumatoid factor and anti-CCP antibodies in RA patients treated with infliximab [2, 8]. The underlying mechanisms whereby anti-TNF could lead to a production of rheumatoid factor are not understood, and reasons of this phenomenon remain speculative. C. Faillace J. F. de Carvalho (&) Rheumatology Division, Clinica de Oncologia (CLION), Rua Altino Seberto de Barros, 119, 7 Andar, Salvador, Bahia 41810-570, Brazil e-mail: jotafc@gmail.com