Background TNF-α antagonism with anti-TNF-α MoAb (Infliximab, Centocor, USA) or soluble TNF-α receptors (Etanercept, Immunex, USA), has emerged as a promising therapeutic tool for refractory chronic arthritis. Both drugs are now licensed for the treatment of refractory RA but experience with TNF-α antagonisers in JIA is limited.
Objectives We report the use of Infliximab in 3 patients with systemic JIA and polyarthritis.
Methods LS (18 yrs) and JD (11 yrs), girls with systemic-onset JIA at the age of 11 and 3, had persistent, destructive polyarthritis. AP (10 yrs), a boy with systemic-onset JIA at the age of 5 had persistent systemic activity as well as severe polyarthritis. All 3 failed NSAID, corticosteroids, (high-dose) MTX and CsA treatment and suffered from severe growth impairment and osteoporosis. All patients started Infliximab therapy at 3 mg/kg (weeks 0, 2, 6 and then 8-weekly). Active joint number (AJN), limited joint number (LJN), visual analogue scale for global well being (VASg) and pain (VASp), Childhood Health Assessment Questionnaire (CHAQ), serum CRP and serum IL-6 were assessed.
Results At present, LS completed 26, JD 38 and AP 86 treatment weeks. LS experienced a manifest decrease in AJN (17 to 1). LJN was unchanged (8). Functional scores decreased markedly: VASg 78 to 10, VASp 45 to 10, CHAQ 1.2 to 0.3. CRP decreased (15 to 3 mg/l) and steroids were tapered from 6 to 3 mg daily. JD showed a similar response: AJN and LJN decreased rapidly (38 to 5 and 41 to 7). VASg, VASp and CHAQ all dropped markedly: 50 to 15, 50 to 10 and 2.1 to 1.4. CRP and ESR decreased (22 to 5 mg/L and 51 to 26 mm/hr). Steroid dose was kept at 4 mg daily. AP experienced a decrease in AJN (9 to 3) and in LJN (12 to 4) during the first 18 weeks. As systemic inflammation persisted, Infliximab dose was increased to 5, later to 10 mg/kg. Whereas AJN and LJN decreased further to 0 and 2, systemic symptoms and the acute phase response persisted: CRP and ESR fluctuated (15–148 mg/l and 45 ? 183 mm/h, respectively). Functional scores varied and reflected the increasing discomfort of preexisting joint damage. Steroid dose was tapered from 12 to 7 mg daily. Infliximab was safe and well tolerated in all 3 patients: possible adverse reactions were fever (AP, once) and upper respiratory tract infection (AP three, JD once). TNF-α blockade with Infliximab in these patients with systemic-onset polyarticular JIA induced a rapid, sustained control of polyarthritis, with concomitant improvement of function, global well being and pain and decrease in biochemical inflammation. Systemic inflammation, however, did not respond to TNF-α blockade. This was evident in patient AP whose articular disease clearly responded but who had a persistent acute phase response with persistently elevated levels of CRP and IL-6.
Conclusion Infliximab is promising for the treatment of JIA. The observed dissociation between response of articular and systemic disease indicates that different cytokine networks may operate in systemic and articular inflammation of JIA.
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