HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN (IVIG) IN SEVERE REFRACTORY RHEUMATOID-ARTHRITIS - NO EVIDENCE FOR EFFICACY

Objective. A number of reports have recently suggested that high doses of intravenous immunoglobulins may exert beneficial effects in rheuma toid arthritis. One proposed mechanism for this effect is suppression of the generation of pro-inflammatory cytokines, particularly tumor ne crosis factor alpha (TNF alpha). We have undertaken a prospective open study of IVIg inpatients with severe refractory RA who have failed at least four second line drugs, including methotrexate, and who were re ceiving NSAIDs and prednisone only. Methods. Four patients, 3 males an d 1 female, with an average age of 58.25 years (range 41 - 69 years) a nd a mean disease duration of 13 years (range 9 - 14 years), were give n IVIg at a dose of 1 g per kg per day for 2 days once a month for 3 m onths. All patients had active disease at baseline as indicated by art average tender joint count of 15 and an average swollen joint count o f 15.25. Clinical assessments were performed according to the WHO/ILAR recommendations at baseline and at monthly intervals up to 4 months a fter the initiation of IVIg therapy. Patients were classified as respo nders or non-responders according to the Paulus criteria. Laboratory a ssessment included a CBC, ESR, and whole blood cytokine ELISA for TNF alpha, TNF R1, and TNF R2 at baseline, 1 day, 7 days and 3 months afte r the initiation of therapy. Results. None of the patients met the Pau lus criteria for either improvement or worsening. Furthermore, increas ed TNF alpha production in lipopolysaccharide (LPS) stimulated whole b lood assays was consistently noted in 3 out of the 4 patients during t he course of therapy which, together with the lack of clinical efficac y prompted us to curtail further evaluation of this therapy. Conclusio n. We were unable to discern any beneficial effects of IVIg therapy, a nd suggestions that it may enhance TNF alpha generation as well as its substantial cost mandate caution in the future use of this agent in R A.