Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis

Abstract

Objectives: To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA).

Methods: Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed.

Results: In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg ⋅ day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock.

Conclusion: Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.ClinicalTrials.gov number NCT02277444.

Keywords: golimumab; intravenous; juvenile idiopathic arthritis; pharmacokinetics; tumour necrosis factor alpha.

Fig. 1

Patient disposition *Adds up to 51 because one patient had more than one reason for ineligibility. AE: adverse event; n: number of patients.

Fig. 2

A–D. Clinical efficacy through week 52 (A) Percentage of JIA ACR 30/50/70/90 responders; N=127; missing data were treated per NRI and LOCF. (B) Percentage of patients with JIA ACR inactive disease or clinical remission on medication; N=127; clinical remission on medication is inactive disease at each visit for ≥6 months while on medication for pc-JIA (all visits encompassing ≥24 weeks prior had to meet inactive disease criteria). For (A) and (B), missing data were treated per LOCF and NRI. (C) Mean (s.d.) CHAQ and parent assessment of pain scores. (D) Mean (95% CI) JADAS 71 scores. 95% CI is based on normal approximation: mean ($1.96)\times \mathrm{s}.\mathrm{d}./\sqrt{N}$. (C) and (D) are based on observed data. BSL: baseline; CHAQ: Childhood HAQ; HDA: high disease activity; ID: inactive disease; JADAS: Juvenile Arthritis Disease Activity Score; LDA: low disease activity; LOCF: last observation carried forward; N: all treated patients; n: number of evaluable patients; NRI: non-responder imputation.

Fig. 3

Observed steady-state serum trough golimumab concentrations (A) and model-predicted AUC_ss (B) at week 28 The horizontal lines within the boxes represent the medians, the lower edges of the boxes represent the first quartile, and the upper edges of the boxes represent the third quartile. Whiskers represent the most extreme observations within the 1.5 × interquartile range. AUC_ss: steady-state area under the curve; n: number of patients in the population; WK: week.