Background Although the biological disease-modifying antirheumatic drugs (bDMARDs) are the most effective treatment for rheumatoid arthritis (RA), the costs are much higher than those of conventional synthetic DMARDs. A number of studies on discontinuation, dose reduction and/or spacing of bDMARDs have been performed, but there have been few reports on increased spacing time between tocilizumab (TCZ) administrations so far.
Objectives To analyze the efficacy of spacing of the intravenous (IV) administration of TCZ in patients with RA.
Methods 63 patients (11 M, 52 F) who were administered IV TCZ for more than 1 year were enrolled. Eleven patients had shifted to subcutaneous injection and the data at the last IV infusion were analyzed.
Results Mean age was 57.4 years old (30–78), mean body weight was 55.5kg (37–85.5), mean duration of illness was 10.7yrs (0–32), The number of the bDMARDs previously administered were 0.9 (0–3), and duration of TCZ treatment was 46.9 months (13–83). The intervals between administrations were 4 weeks: 28.6%, 5 weeks: 38.1%, 6 weeks: 17.5%, 7 weeks: 6.0%, 8 weeks: 7.9%, and 10 weeks: 1.6%. Tender joint count, swollen joint count, erythrocyte sedimentation rate (ESR), C-reactive protein, matrix metalloproteinase-3 (MMP-3), patient's visual analogue scale (VAS), doctor's VAS, disease activity score (DAS) 28-ESR, simplified disease activity index (SDAI), clinical DAI (CDAI) were significantly improved. All of patients remission rates were 90.5% for DAS28-ESR, 44.4% for CDAI, and 42.9% for SDAI. Patients with prednisolone (PSL) decreased from 50 to 38 (p=0.031), at doses of 5.3 (2–10) to 2.7 (0.5–5) mg/day (p<0.0001). Patients with methotrexate (MTX) decreased from 46 to 32 patients (p=0.017), at doses of 8.1 (2–18) to 6.6 (2–14) mg/weeks (p<0.0001). There were no changes in the usage of other csDMARDs. The remission rates of the patients with increased spacing (n=45) were 75.6% for DAS28-ESR, 28.9% for CDAI, and 35.6% for SDAI. In 45 patients with increased spacing, both PSL and MTX were significantly reduced even after spacing (2.9: 0.5–5.5 to 2.6: 1–7.0) mg/day, and (6.45: 2–10 to 5.2: 2 -12) mg/ weeks, respectively (p=0.0013, p=0.0085). At the introduction of TCZ, there was no difference in the serum levels of MMP-3 in patients with increased spacing and without spacing 274.8 (24–1310) ng/ml vs 283.3 (32–626) ng/ml p=0.692). Serum revels of MMP-3 at the first time of increased spacing were significantly lower in the patients with increased spacing than those at the final point of patients without spacing 72.0 (22.2–236.0) ng/ml vs 165.8 (35.8 -619.0) ng/ml, p=0.000752. The number of patients with normal levels of MMP-3 among the patients with increased spacing were 25/45 (55.6%) with significantly higher levels for those patients who had no spacing 3 /18 (16.7%, p=0.00567).
Conclusions TCZ treatment was associated with significantly reduced disease activity and reduced use of PSL and MTX. Increased spacing between administrations was used in 71.4% of the patients. TCZ was able to reduce PSL and MTX even after spacing. MMP-3 might be a useful marker to decide the spacing period. TCZ is the most inexpensive bDMARD in Japan, but with increased spacing, it is possible to reduce the cost even further with acceptable control of RA symptoms.
Disclosure of Interest None declared