Ozoralizumab shows effectiveness regardless of baseline RF and ACPA titres in patients with RA: a post hoc analysis of the OHZORA trial

Abstract

Objectives: Ozoralizumab (OZR) is a next-generation anti-TNF NANOBODY® compound. The primary objective was to evaluate the efficacy of OZR in patients with RA in varying RF and anti-citrullinated peptide antibody (ACPA) titres. The secondary objective was to evaluate the changes in RF and ACPA titres following OZR treatment.

Methods: A post hoc analysis was conducted on data from the Phase II/III OHZORA trial, which included 381 Japanese patients with RA who were treated with either 30 or 80 mg OZR over 52 weeks after demonstrating an inadequate response to MTX. Patients were classified into four groups based on the baseline RF or ACPA titre quartiles. The disease activity scores, RF and ACPA titres, plasma OZR concentrations and OZR-neutralizing antibody levels were evaluated. Statistical analyses included the Kruskal-Wallis test, two-way ANOVA and correlation analysis.

Results: Treatment with OZR 30 mg significantly reduced disease activity in all the groups (P < 0.001), and the reduction in disease activity scores was comparable among the groups. Treatment with OZR 30 mg decreased the mean RF and ACPA titres from 149.5 to 71.1 IU/ml (P < 0.001) and 299.6 to 237.6 U/ml (P < 0.001), respectively. Effective trough concentrations of OZR were maintained for up to 52 weeks in all the groups, and baseline RF and ACPA titres were not associated with the generation of OZR-neutralizing antibodies.

Conclusion: OZR is an effective anti-TNF treatment for RA, regardless of RF and ACPA titres, and exhibits promise as a novel therapeutic option.

Keywords: NANOBODY®; RA; RF; VHH antibody; inhibitor; ozoralizumab; tumour necrosis factor-α.

Graphical abstract

Figure 1.

Ozoralizumab (OZR) 30 mg effectively controlled disease activities over 52 weeks irrespective of baseline RF titres. A total of 143 patients who received OZR 30 mg over 52 weeks were classified into four groups based on the baseline RF titre quartiles (RF1: RF 3–20 IU/ml, RF2: 20–49 IU/ml, RF3: 49–153 IU/ml, RF4: 153–2029 IU/ml), and changes in (A) DAS28-CRP, (B) DAS28-ESR, (C) CDAI and (D) SDAI were shown. Data are shown as mean ± SD. The last observation carried forward method was used. CDAI, clinical disease activity index; DAS28-CRP, disease activity score using CRP; DAS28-ESR, disease activity score using ESR; ns, not significant; SDAI, simplified disease activity index. ***P < 0.001

Figure 2.

Ozoralizumab (OZR) 30 mg effectively controlled disease activities over 52 weeks irrespective of baseline anti-citrullinated peptide antibody (ACPA) titres. A total of 143 patients who received OZR 30 mg over 52 weeks were classified into four groups based on the baseline ACPA titre quartiles (ACPA1: 0.5–25.9 U/ml, ACPA2: 25.9–103 U/ml, ACPA3: 103–426 U/ml, ACPA4: 426–1200 U/ml), and changes in (A) DAS28-CRP, (B) DAS28-ESR, (C) CDAI and (D) SDAI were shown. Data are shown as mean ± SD. The last observation carried forward method was used. CDAI, clinical disease activity index; DAS28-CRP, disease activity score using CRP; DAS28-ESR, disease activity score using ESR; ns, not significant; SDAI, simplified disease activity index. ***P < 0.001

Figure 3.

RF titre reduction by ozoralizumab (OZR) treatment. The mean change (A) and percent change (B) of the RF titre in patients who received OZR 30 mg. The mean change of RF titre (C) and RF reduction (D) in each RF titre group. Data are shown as mean ± SD. ***P < 0.001

Figure 4.

Anti-citrullinated peptide antibody (ACPA) titre reduction by ozoralizumab (OZR) treatment. The mean change (A) and percent change (B) of ACPA titre in patients who received OZR 30 mg. The mean change of ACPA titre (C) and ACPA reduction (D) in each ACPA titre group. Data are shown as mean ± SD. ***P < 0.001