Background/Purpose: Tofacitinib is an oral JAK inhibitor that is being investigated for JIA. Here we assess the efficacy and safety of tofacitinib in patients (pts) with JIA.

Methods: This was a Phase 3, randomized, double-blind (DB), placebo (PBO)-controlled withdrawal study in pts aged 2 to < 18 years with polyarticular course JIA (pcJIA), PsA or enthesitis-related arthritis (ERA) (NCT02592434). In the 18-week, open-label (OL), run‑in phase (Part 1), pts received tofacitinib. Pts achieving ≥ JIA ACR30 response¹ at Week (W)18 were randomized 1:1 in the DB phase (W18−44; Part 2) to continue receiving tofacitinib or withdraw tofacitinib and newly receive PBO. Tofacitinib was administered according to body weight: 2−4 mg BID oral solution in pts < 40 kg; 5 mg BID tablet or oral solution in pts ≥ 40 kg. The primary endpoint was occurrence of disease flare² by W44 (W26 of Part 2). Key secondary endpoints were JIA ACR50/30/70 response¹ rates and change (∆) from Part 2 baseline (BL) in Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) at W44. The primary and key secondary endpoints were type 1 error-controlled with statistical significance declared at p < 0.05. Other efficacy endpoints included time to disease flare in Part 2, ∆ from Part 1 BL in JIA ACR core set variables¹ at W44, and ∆ from Part 2 BL in Juvenile Arthritis Disease Activity Score (JADAS27-CRP) during Part 2. Pts with PsA or ERA were excluded from these efficacy analyses and analyzed separately. Time to flare was analyzed by the Kaplan-Meier method. Safety was evaluated throughout the study.

Results: 225 pts with pcJIA (n=184), PsA (n=20) or ERA (n=21) were enrolled and received OL tofacitinib in Part 1 (Table 1). At W18, 173/225 (76.9%) pts entered Part 2 (pcJIA [n=142], PsA [n=15], ERA [n=16]). In pts with pcJIA, occurrence of disease flare in Part 2 was significantly lower with tofacitinib (29.2%) vs PBO (52.9%) by W44 (p=0.0041; primary endpoint; Figure 1a). JIA ACR50/30/70 response rates (Figure 1b) and improvement from Part 2 BL in CHAQ-DI (Figure 1c) at W44 were greater with tofacitinib vs PBO. Time to disease flare was greater with tofacitinib vs PBO in Part 2 (Figure 1d). Tofacitinib had a greater effect vs PBO in reducing signs and symptoms of pcJIA, in terms of ∆ from Part 1 BL in JIA ACR core set variables at W44 (Figure 1e). From early time points in Part 2, disease activity (assessed by JADAS27-CRP) worsened with PBO but remained stable with tofacitinib (Figure 1f). Safety was generally similar in pts receiving tofacitinib or PBO (Table 2): 77.3% and 74.1% had adverse events (AEs); 1.1% and 2.4% had serious AEs. There were no cases of death, opportunistic infection or tuberculosis.

Conclusion: In pts with pcJIA, treatment with tofacitinib vs PBO resulted in significantly fewer disease flares, improved time to flare, improvements in disease signs and symptoms and physical functioning, and a sustained clinically meaningful improvement in disease activity. The safety profile of tofacitinib was consistent with that in adults with RA.

1. Giannini EH et al. Arthritis Rheum 1997; 40: 1202-1209.
2. Brunner HI et al. J Rheumatol 2002; 29: 1058-1064.

Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-for-the-treatment-of-polyarticular-course-juvenile-idiopathic-arthritis-results-of-a-phase-3-randomized-double-blind-placebo-controlled-withdrawal-study/