AB0380 Experience with Rituximab in The Management of Recurrent Tocilizumab Induced Macrophage Activation Syndrome in An Adult Patient with Systemic-Onset Juvenile Idiopathic Arthritis (Still's Disease)
Authors: Y. Muraviev, V. Lebedeva, S. Soloviev, N. Nokanorova, E. Nikolaeva, V. Khlaboschina, L. Bozhieva
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Macrophage activation syndrome (MAS) is a potentially fatal complication of Still9s disease (SD). The use of <i>biologic disease-modifying antirheumatic drugs</i> (bDMARDs) has significantly improved the prognosis in SD pts, although most recent reports on MAS linked to use of bDMARDs in SD patients raise certain concern. <h3>Objectives</h3> To share the experience from the use of bDMARD for management of MAS, induced by other bDMARDs in an adult patient with SD. <h3>Methods</h3> Description of a case of successful rituximab therapy for MAS, induced by tocilizumab in an adult SD patient. <h3>Results</h3> In a patient Sh.,18 yo, the onset of SD occurred in December 2008y (at the age of 14 y.o.), manifesting with fever 39°C, arthralgia, lymphadenopathy, hepatosplenomegaly, neutrocytosis, maculopapular rash, ESR up to 40 mm/h, CRP 48 mg/L. Prednisone (50 mg/day) was discontinued shortly due to emergence of multiple duodenal ulcers (EFGDS), which resulted in increasing CRP up to 154 mg/L, anemia (nv-89 g/L), neutrocytosis up to 14,7x10<sup>9</sup>, elevated ALT and AST &gt;120 EU/L, LDH 735 U/L, and ferritine &gt;12000 μg/L. This condition progressed to tonic-clonic seizures and coma, leucopenia (4,5x10<sup>9</sup>), and thrombocytopenia (33x10<sup>9</sup>). MAS was documented. GCs were re-administered (prednisone 50 mg/day, methylpred pulse-therapy), sandimmun was also commenced at 200 mg/day dose. By 2013 y. the dose of prednisone was down-titrated to 2,5 mg/day and of sandimmun - to 100 mg/day. At this dose level a relapse of fever 38,5° C, arthralgia, pharyngalgia and rash on the forearms occurred. The dose of prednisone was up-titrated to 20 mg/day, but arthralgia and ubnormal lab parameters of active disease persisted (ferritine, CRP, ESR), necessitating administration of tocilizumab (8 mg/kg). But second infusion of tocilizumab caused severe adverse reaction (dyspnea, drop of BP, nausea, dizziness) with MAS reoccurrence (fever 39,5° C, thrombocytopenia, anemia, elevated liver enzymes, ferritine, hypofibrinogenemia, hypertriglyceridemia), necessitating up-titration of methylpred dose up to 40 mg/day, pulse therapy with methylpred and dexamethasone, IVIG (2.5 g/kg total dose), SAMe. Associated pneumonia was successfully cured with antibiotics (CT verified). Rituximab 1000 mg was administered i/v by drop infusion, and repeated after 6 mo. Currently the patient does not voice any specific complaints, her lab parameters are constantly normal (remission), the methylpred dose was down-titrated to 4 mg/day. <h3>Conclusions</h3> Presented case, on one side, raises the appropriateness of updating the summary of product characteristics&amp;directions for tocilizumab use in package circular/prescribing info, and on the other side, confirms the usefulness of rituximab for refractory Still9s disease, complicated with MAS. <h3>Disclosure of Interest</h3> None declared