**6. Improving clinical outcomes**

#### **6.1 Strategies for improving clinical outcomes**

The response rate and the speed of improvement basically depend on the ratio between the target cytokine and the biological agent which traps the target cytokine. To lessen the amount of the target cytokine, it is very important that any comorbidity (e.g., infectious diseases, lifestyle diseases, etc.) is treated or controlled as well as possible before and during administration of biological agents. This not only stops stimulation of the production of inflammatory cytokines from factors other than RA, but also serves to reduce adverse events, which results in better efficacy and safety. This also directly improves physical function irrespective of disease activity (Radner et al., 2010).

The standard dosage of TCZ for the treatment of RA is 8 mg/kg every 4 weeks. The serum TCZ concentrations 4 weeks after 3 doses are greater than 1 mg/mL, which is an effective dose, in about 80% of patients. However, this means that the serum TCZ concentrations are not sufficiently high in approximately 20% of patients. In these patients, increasing the dosage of TCZ and/or shortening the dosage interval may improve efficacy. Indeed, during clinical trials, it was observed that arthritis improved following the first dose but returned after 3 weeks in several patients. This suggested that the blood level could not be maintained over the 4-week period. I thus decided to give the second dose after an interval of 3 weeks following the first. By doing this, none of the patients suffered repeat deterioration by the time of the second dose in symptoms that had improved following the first, and no additive adverse effects were observed. A shorter dose interval at the start may be thought to be perfectly reasonable in terms of maintaining blood levels of biologics. In practice, this administration method is used for infliximab and abatacept.
