Background/Purpose:

Biologic agents have dramatically improved the outcome of rheumatoid arthritis (RA) patients. However, the administration dose and treatment intervals of these agents are usually fixed for individual patients. Hence, patients displaying disease remission receive an unnecessary high dose of medication. The immunosuppressive action of biologics in this medication strategy exposes patients to a high risk to gain infectious diseases and causes increased medical costs. In this study, we optimized the treatment intervals of the biologics tocilizumab and golimumab by monitoring their serum trough levels in individual patients.

Methods:

Japanese RA patients were treated either with intravenous tocilizumab (TCZ) 8mg/kg or subcutaneous golimumab (GLM) 50mg every 4 weeks (n=49 or n=20, respectively) and enrolled to analyze their serum trough levels of the respective biologics. Recombinant human soluble IL-6 receptor or human TNFα was coated on ELISA plates and bound TCZ or GLM in patient sera was detected with anti-human IgG1 antibody. The disease activity was evaluated with DAS-CRP. Treatment intervals were prolonged for patients with low disease activity displaying tocilizumab or golimumab serum trough levels>1μg/ml.

Results:

We monitored significant differences of the serum trough levels of the respective agent among individual patients. TCZ ranged from 0.25μg/ml to 52μg/ml (17.4 ± 10.4μg/ml), while GLM ranged from 0.25μg/ml to 10.9μg/ml (3.34 ± 3.13μg/ml).  A positive correlation between age and serum trough levels was found in the TCZ group (P=0.0101, r²=0.3863).  However, we did not find any correlation between the disease activity and serum trough levels of the biologics in both TCZ and GLM groups. In the TCZ group, the mean trough level was 16.8μg/ml ± 8.1μg/ml  at 4-weeks and was reduced to 11.1μg/ml ±9.0μg/ml after 5-weeks and 3.09μg/ml ±3.29μg/ml after 6-weeks.  24 patients with low disease activity displaying serum trough level >1μg/ml of TCZ agreed to prolong treatment intervals. 13 of the 24 patients showed a TCZ serum level >1μg/ml even after prolongation  of medication without any disease exacerbation. However, 11 of 24 patients displayed a decreased TCZ serum trough level <1μg/ml. In this group 3 patients had a increased DAS-CRP score whereas in 8 patients the disease activity was not affected. In the GLM group, the mean trough serum level was 3.34μg/ml ± 3.13μg/ml after 4-weeks and was reduced to 2.85 μg/ml ± 2.51μg/ml after 5-weeks and 1.41μg/ml after 6-weeks. The disease activity didn’t change after modification of the medication interval.

Significant difference of serum trough levels of biologics was observed among RA patients treated with TCZ or GLM. Maintenance of a certain serum trough levels by monitoring concentration of biologics may allow optimization of treatment intervals without increasing the disease activity and may lead to decrease medical costs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/optimization-of-treatment-intervals-of-tocilizumab-and-golimumab-by-measuring-serum-trough-levels-in-rheumatoid-arthritis-patients/