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THU0223 Treatment of a patient with nonclassified hla b27 associated destructive oligoarthritis with anti tnf: clinical outcome and effects on nf-kappa b activity in pbmc
1. T Geiler,
2. R Voll,
3. HM Lorenz,
4. C Dechant,
5. B Manger,
6. JR Kalden
1. Department of Medicine III, University of Erlangen-Nuremberg, Erlangen, Germany

## Abstract

Background We report the case of a 38 years old HLA B27 positive male with a 11 year history of a destructive nonclassified oligoarthritis. While the first 6 years of the disease have been dominated by a relapsing nondestructive synovitis of the right knee joint and a asymptomatic sacroileitis treated with NSAIDs alone the disease began to spread in a destructive manner to the right wrist and foot (MTP I-V, PIP I-V, DIP I-V). Additionally, a painful tenosynovitis of the flexor and extensor tendons of both feet occured. Despite intensifying the pharmacological treatment by high doses of corticosteroides (up to 100 mg/d) and methotrexate (25 mg/week) for 9 month the disease showed significant clinical and radiological progress. No reduction of the constantly elevated ESR and CRP could be achieved. By initiating a therapy with anti TNF (Remicade TM) at a dose of 5 mg/kg body weight all clinical symptoms disappeared completely within 8 h after the first infusion of the antibody. ESR and CRP normalised within 6 days. The patient stayed completely free of symptoms since, side effects have not been detected by now. Repeated infusions after 2, 4, 6 and 14 weeks did not further improve the therapeutic benefit but were given to sustain the therapeutic effect.

Objectives Since TNF is known as a strong activator of NF-κB which is strongly involved in the production of proinflammatory cytokines and matrix metalloproteinases we looked for the activity of this transcription factor in PBMCs of this patient by electro mobility shift assays (EMSA).

Methods Cells were obtained immediately before the infusions were started and 1 h and 24 h after end of infusions. Cell preparations and EMSA were done according standard protocols.

Results There was substantial NF-κB activity in PBMCs before first antibody treatment. Anti TNF treatment decreased NF-κB activity detectable already 1 h after first infusion. The NF-κB activity was further inhibited 24 h after first infusion and remained low during the whole treatment period in accordance to the persisting clinical improvement.

Conclusion In the treatment of patients with progressive nonclassified HLA B27 oligoarthritis resistent to classical treatment with NSAIDs, corticosteroids and DMARD`s the use of TNF blocking agents should be considered. As in other destructive inflammatory joint diseases NF-κB might play a crucial role in the pathogenesis of joint destruction in HLA B27 associated arthritides. The clinical improvement appears to be associated with a persistent and marked inhibition of NF-kappa B.

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