EU Approves Tofacitinib Citrate for 2 Pediatric Conditions

In August, the European Commission (EC) approved tofacitinib citrate (Xeljanz) to treat two pediatric conditions, as well as a prolonged-release version of the medication designed to treat adults with active psoriatic arthritis (PsA).

Active Polyarticular JIA & Juvenile PsA

The EC approved tofacitinib citrate to treat active polyarticular juvenile idiopathic arthritis (pJIA) and juvenile PsA. The approvals were for patients aged 2 years and older for whom treatment with disease-modifying anti-rheumatic drugs (DMARDs) proved inadequate.¹

JIA is the most common type of arthritis in patients younger than 16, and pJIA and juvenile PsA are two of the six subtypes.^2,3 pJIA, which occurs in about 25% of children with JIA, affects at least five joints—often on both sides of the body—and may affect both large and small joints.

In patients with juvenile PsA, joint symptoms and a scaly rash behind the ears and/or on the eyelids, elbows, knees, belly button and scalp may occur. Affected joints may include the wrists, knees, ankles, fingers or toes. Patients may exhibit joint pain and stiffness, swelling and reduced range of motion. Skin symptoms may occur before or after joint symptoms appear.

Background: These EC approvals were based on data from a phase 3 study in patients (n=225) age 2–18 years with pJIA (n=184), as well as other JIA subtypes (n=20), including juvenile PsA (n=21; NCT02592434).⁴ The 44-week, randomized, withdrawal, double-blind, placebo-controlled study evaluated the efficacy and safety of tofacitinib citrate in this patient population. The study had two phases: an 18-week, open-label, run-in phase (phase 1), followed by a 26-week double-blind, placebo-controlled, randomized, withdrawal phase (phase 2).⁵

At the end of phase 1, only patients who achieved the primary end point of at least a JIA ACR30 response were randomized to phase 2 (n=173). This primary end point is defined as at least a 30% improvement from baseline in any three of the following six response variables in patients with JIA:

1. Number of joints with active arthritis (swelling/in absence of swelling, limited range of motion accompanied by pain/tenderness);
2. Number of joints with limited range of motion;
3. Physician global evaluation of disease activity (assessed on a Visual Analog Scale [VAS] of 0 [no activity] to 10 [maximum activity]);
4. Parent/legal guardian/participant global assessment of overall wellbeing (assessed on VAS of 0 [very well] to 10 [very poor]);
5. Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI): 30 questions in eight domains, each question answered on scale of 0 (without difficulty) to 3 (unable to do); scores of each domain were averaged to derive total CHAQ-DI score, which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction); and
6. Erythrocyte sedimentation rate (ESR).

In phase 2 of the study, 142 patients had JIA, 15 had PsA and 16 had other JIA subtypes. Disease flare was defined as a 30% or more worsening in at least three of the six core response variables of the above variables, with no more than one of the remaining core response variables improving by at least 30% after randomization—an outcome measure used in JIA clinical trials.