Background/Purpose:  The all-patient PMS study of tocilizumab (TCZ) followed 7901 RA patients for 28 wks. That study (hereafter, PMS7901) showed patients with a high probability of remission and a low probability of developing serious infection to be those most likely to have early and less advanced RA and to have not received biologics previously. The FIRST Bio study is designed to investigate effectiveness and safety of TCZ in RA patients who had not received any biologics (i.e. bio-naïve) in a real clinical setting.

Methods: FIRST Bio is a 52-wk observational postmarketing surveillance study which enrolled bio-naïve RA patients who met the ACR/EULAR 2010 classification criteria for RA, experienced inadequate response or were intolerant to one or more DMARDs, and had DAS28-ESR > 3.2. Patients received 8 mg/kg TCZ every 4 wks intravenously with or without DMARDs at the investigators’ discretion. Patient characteristics and safety and effectiveness data were collected. This interim analysis reports the results of 24 wks’ observation. A paired t-test was used to detect statistically significant differences in disease activity (CDAI, DAS28-ESR) and Health Assessment Questionnaire (HAQ) score compared to baseline.

Results:  This report analyzes 551 of 855 patients enrolled. Mean disease duration and percentage of patients who had less advanced Steinbrocker’s stage and class and had comorbidities were lower in the FIRST Bio study than in PMS7901 (Table 1). At Wk 24, 87.2% of patients were continuing TCZ treatment. Mean CDAI improved from 23.4 at baseline to 7.5 at Wk 24 (p < 0.0001). DAS28-ESR also improved from 5.2 at baseline to 2.2 at Wk 24 (p < 0.0001). At Wk 24, rate of CDAI remission (CDAI ≤ 2.8) was 30.9%, DAS28-ESR remission (DAS28-ESR < 2.6) was 66.5%, and Boolean remission was 27.8%. The Boolean remission rate in the FIRST Bio study was almost twice that in PMS7901 (15.1%) (Table 2). The mean HAQ score improved from 1.0 at baseline to 0.5 at Wk 24 (p < 0.0001), and in 59.8% of patients the HAQ score decreased to <0.5 (i.e. HAQ remission). The incidence rates of total and serious AEs were 25.2% and 6.4%, respectively. Infections were the most frequent AEs (6.4%) and the most frequent serious AEs (2.0%). Malignancies were reported in 2 patients (0.4%). Gastrointestinal disorders were reported in 19 patients (3.4%), including 1 (0.2%) gastrointestinal tract perforation. One patient died (0.2%). The incidence rates of serious AEs and serious infections were lower in the FIRST Bio study than in PMS7901 (Table 2). Mean dose of concomitant MTX decreased from 9.1 mg/wk at baseline to 7.3 mg/wk at Wk 24. Mean dose of concomitant corticosteroid also decreased from 5.7 mg/day at baseline to 3.6 mg/day at Wk 24.

Conclusion:  The FIRST Bio study revealed that in the real clinical setting TCZ showed high effectiveness and safety in those patients who have less advanced RA and who have not previously received biologics.

 

Table 1.  Patient background	FIRST Bio study	PMS7901
Mean age (SD), years	59.4 (13.7)	58.7 (12.9)
Mean disease duration (SD), years	7.2 (8.7)	10.4 (9.2)
% of patients (pts) whose Steinbrocker’s stage was I or II	63.5	35.2
% of pts whose Steinbrocker’s class was 1 or 2	81.5	73.8
% of pts who had any comorbidities (% of pts who had respiratory disease as comorbidity)	56.8 (11.3)	70.6 (14.5)
% of pts with prior use of biologics	0	62.8
% of pts with concomitant use of MTX (mean dose in pts using MTX)	60.8 (9.1mg/wk)	55.8 (7.0mg/wk)
% of pts with concomitant use of corticosteroids (mean dose in pts using corticosteroids)	55.4 (5.7mg/day)	74.0 (5.3mg/day)
Table 2. Comparing safety and effectiveness	FIRST Bio study At Wk 24	PMS7901 At Wk 28
Boolean remission rate, %	27.8	15.1
Incidence rate of AEs (serious AEs), %	25.2 (6.4)	43.9 (9.6)
Incidence rate of infections (serious infections), %	6.4 (2.0)	11.0 (3.7)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effectiveness-and-safety-of-tocilizumab-in-biologics-naa%c2%afve-ra-patients-interim-analysis-of-pms-for-investigating-success-in-achieving-clinical-and-functional-remission-and-sustaining-eff/