Rituximab May Hold Promise in Treating IgG4-RD

IgG4-related disease (IgG4-RD), a systemic disease that can affect any part of the body and can involve fibrosis, irreversible organ damage, and secondary amyloidosis, is a rare immune-mediated condition often treated with corticosteroids or immunosuppressive drugs. The pathogenesis of the disease is not clear, but treatment with B-cell depletion therapy, in the form of rituximab, has shown positive results in some patients.

A recent paper, appearing in The Netherlands Medical Journal, describes a study evaluating different treatment outcomes in a well-defined cohort of 32 patients—72% of whom were male and who had a mean age of 57 years (range, 17-77)—with IgG4-RD. All were treated at the Erasmus University Medical Center between 1999 and 2017. The patients received therapies including corticosteroids; the immunosuppressive drugs mycophenolate mofetil, methotrexate, and azathioprine; hydroxychloroquine, cyclophosphamide, rituximab, thalidomide, and infliximab. Disease activity was evaluated using the IgG4-related disease Responder Index (IgG4-RD RI).

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In total, 91% of the patients were first treated with corticosteroids (the remaining patients took methotrexate followed by hydroxychloroquine or surgery, leading to complete response), but 62% eventually required additional steroid-sparing treatment:

• 7 patients next took methotrexate, but only 2 responded to treatment.
• 12 patients were given azathioprine, with only 1 patient achieving a complete response and with 6 terminating treatment because of toxicity.
• 3 patients took mycophenolate mofetil, but only 1 responded adequately.
• 3 patients received cyclophosphamide, and only 1 responded adequately, and this response was temporary.
• 1 patient took cyclosporine A without effect.
• 1 patient achieved remission after taking thalidomide, but experienced neurological adverse events.
• 1 patient took infliximab and achieved complete remission that has been maintained for 5 years.
• 6 patients took rituximab, in most cases as a third-line treatment, and all achieved a response: 3 experienced a complete response, and 3 achieved a partial response, although the effects of rituximab were temporary.

Because the effect of immunosuppressive small-molecule drugs was limited, and because rituximab appeared to be able to produce substantial responses, the authors concluded, rituximab maintenance treatment is a potentially effective strategy in patients with relapses, although this finding needs to be investigated in future studies.

Reference

Karim AF, Bansie RD, Rombach SM, et al. The treatment outcomes in IgG4-related disease. Neth J Med. 2018;76(6):275-285. PMID: 30152392.