Reduced dose of tocilizumab for the maintenance of remission in patients with rheumatoid arthritis: a clinical experience.

Abstract

disease activity after dose reduction regained low disease activity after returning to the standard dose. The study by van Herwaarden et al. paved the way for further investigation on the effectiveness of reduced-dose TCZ in clinical practice. At our center, we conducted a small pilot, descriptive-only observation in ten RA patients who were under therapy with standard-dose TCZ from at least 12 months and in clinical remission from at least 6 months. After informed consent, TCZ therapy was reduced to 4 mg/kg. Each month, at the infusion visit, patients were monitored using approved clinical scales (VAS, HAQ, CDAI, and SDAI) and by ultrasound (US) examination, which is increasingly used in the determination of disease progression [5]. One patient developed a neoplasia and was then excluded from the analysis. Two patients experienced reactivation of disease, 2 and 4 months since the initiation of reduced-dose TCZ, respectively; standard-dose TCZ therapy was then reinstituted, and clinical remission was observed at the following visit in both patients. We report here the data reported at 12 months after the initiation of reduced-dose TCZ, in the remaining seven patients. Overall, at the end of the observation period, all patients showed stable disease remission, although a minor worsening in all scales was observed (mean DAS28-VES: 1.7 ± 1.1 at baseline vs. 2.4 ± 1.2 at 12 months; DAS28-PCR: 1.5 ± 0.8 vs. 2.2 ± 0.5; HAQ: 0.1 ± 0.4 vs. 0.2 ± 0.4; CDAI: 3.1 ± 2.9 vs. 4.7 ± 2.8; SDAI: 3.2 ± 2.9 vs. 4.8 ± 2.8). Disease remission was also confirmed at US (number of joints with articular effusion: 4.0 ± 2.5 vs. 5.7 ± 4.1; number of joints with synovial hypertrophy: 4.7 ± 2.8 vs. 6.6 ± 4.4; number of positive joints at Power Doppler: 0.7 ± 1.0 vs. 0.6 ± 0.8). Although the preliminary and descriptive-only nature of our pilot analysis does not allow to retrieve any definite conclusion, our findings lend further support to the Tocilizumab (TCZ) is a humanized monoclonal interleukin-6 (IL-6) receptor antibody which has demonstrated clinical efficacy in the treatment of patients with moderate–severe rheumatoid arthritis (RA) who experienced inadequate response to methotrexate and one or more antiTNFα agent [1, 2]. The efficacy of TCZ in the treatment of RA is supported by a bulk of evidence which includes randomized clinical trials and observational, ‘field-practice’ studies [2]. TCZ can be administered intravenously at the standard dose of 8 mg/kg either in combination with other disease-modifying antirheumatic drugs (DMARDs) or as a monotherapy [2]. The favorable efficacy and tolerability profile of TCZ is sustained over a long term (up to 9 years) [2]. Although the above-mentioned evidence supports the use of TCZ in clinical practice, additional data are required to fully explore the optimal individualization of this treatment for each single patient [3]. For instance, it has been recently suggested that some of patients on TCZ achieve low disease activity with a lower than registered starting dose, i.e., 4 mg/kg [4]. In a retrospective study by van Herwaarden et al. [4] on 22 RA patients treated with TCZ 8 mg/kg for about 6 months and tapered to 4 mg/kg because of low disease activity, 55 % of patients remain in disease remission at 6 months since the reduction in dose; however, a slight increase in the disease activity score 28 (DAS28) was observed at the end of the observation period. Interestingly, all patients with worsened