High dose intravenous immunoglobulin (IVIg) in severe refractory rheumatoid arthritis: no evidence for efficacy

A number of reports have recently suggested that high doses of intravenous immunoglobulins may exert beneficial effects in rheumatoid arthritis. One proposed mechanism for this effect is suppression of the generation of pro-inflammatory cytokines, particularly tumor necrosis factor alpha (TNF alpha). We have undertaken a prospective open study of IVIg in patients with severe refractory RA who have failed at least four second line drugs, including methotrexate, and who were receiving NSAIDs and prednisone only.

Four patients, 3 males and 1 female, with an average age of 58.25 years (range 41-69 years) and a mean disease duration of 13 years (range 9-14 years), were given IVIg at a dose of 1 g per day for 2 days once a month for 3 months. All patients had active disease at baseline as indicated by an average tender joint count of 15 and an average swollen joint count of 15.25. Clinical assessments were performed according to the WHO/ILAR recommendations at baseline and at monthly intervals up to 4 months after the initiation of IVIg therapy. Patients were classified as responders or non-responders according to the Paulus criteria. Laboratory assessment 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 after the initiation of therapy.

None of the patients met the Paulus criteria for either improvement or worsening. Furthermore, increased TNF alpha production in lipopolysaccharide (LPS) stimulated whole blood assays was consistently noted in 3 out of the 4 patients during the course of therapy which, together with the lack of clinical efficacy, prompted us to curtail further evaluation of this therapy.

We were unable to discern any beneficial effects of IVIg therapy, and suggestions that it may enhance TNF alpha generation as well as its substantial cost mandate caution in the future use of this agent in RA.