Background/Purpose: Juvenile idiopathic arthritis (JIA) often requires biologic medication to control polyarticular disease courses. This study assesses the pharmacokinetics (PK), efficacy and safety of certolizumab pegol (CZP)±MTX in children and adolescents with moderate to severe polyarticular-course JIA.

Methods: PASCAL (NCT01550003) is an ongoing, multi-center, open-label study for patients (pts) aged 2–<18 years (yrs), weight ≥10 kg, with signs and symptoms of JIA for ≥6 months and prior history of DMARD use. Pts were enrolled from 7 PRCSG-PRINTO countries in North/South America and Russia. Original CZP doses were weight-adjusted based on simulations from a population PK model (adult rheumatoid arthritis [RA] data): pts 10–<20kg received a loading dose (LD; Week [Wk] 0, 2, 4) of CZP 100 mg and maintenance dose (MD; Q2W) of CZP 50 mg; 20–<40 kg, LD CZP 200 mg and MD CZP 100 mg; ≥40 kg, LD CZP 400 mg and MD CZP 200 mg. Interim analyses revealed higher CZP plasma trough concentrations than the target range (C_trough geometric mean in adult RA pts: 15.7 µg/mL [95% CI: 14.0–17.7]). Thus, MD was reduced by 50% and additional pts were enrolled with 50% reduction in LD and MD. Non-responder imputation and last observation carried forward were used for binary and continuous efficacy endpoints, respectively.

Results: Of 163 pts: 78 enrolled on the Original Dose Regimen (ODR) with dose reduction as early as Wk 12; 85 pts enrolled on the Reduced Dose Regimen (RDR). Overall, 68.7% were female, median (min, max) age of 12.0 (3, 17) yrs, 2.0 (0.5, 14.7) yrs since diagnosis. At Wk 12, C_trough values were higher than target range for ODR pts but largely within range for RDR pts, with lower exposure in 10–<20 kg pts. 15.4% of ODR pts and 28.2% of RDR pts were anti-CZP antibody positive, with no apparent impact on efficacy or safety. At Wk 16, JIA ACR30 responses were achieved by 79.2% of ODR pts and 80.0% of RDR pts. JIA ACR 50/70/90 responses were similar across the two dosing regimens (Table A). Clinically inactive disease (CID) was seen in 2.6% of ODR pts and 9.4% of RDR pts. Improvements were also observed in JADAS-71 score for ODR and RDR pts. Efficacy improvements were maintained through Wk 24 (Table A). The incidence rate (IR) of AEs was similar for ODR and RDR pts, with no new safety signals (Table B). The most common class of AE was infection and infestation. There were 2 deaths among RDR pts (CZP 100 mg): 1 was a road traffic accident in a 16 yr old pt considered unrelated to CZP±MTX, the other occurred post Wk 24 in an 18 yr old Mexican pt and is described by the investigator as hepatic tuberculosis and septic shock, considered related to CZP±MTX treatment at the time of onset.

Conclusion: For JIA pts on RDR, distribution of CZP plasma concentrations fell largely within the range seen in adult RA pts. Clinically-relevant JIA improvement was observed across all weight groups by Wk 16 and maintained to Wk 24. The safety profile of CZP seemed in line with that of other anti-TNFs approved for JIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-multi-center-open-label-study-to-assess-the-pharmacokinetics-efficacy-and-safety-of-certolizumab-pegol-in-children-and-adolescents-with-moderately-to-severely-active-polyarticular-course-juvenile/