Statistics from Altmetric.com
Bortezomib belongs to the family of proteasome inhibitors and is a well established first line drug in multiple myeloma (MM).1 In mouse models of lupus nephritis, bortezomib ameliorated glomerulonephritis, prolonged survival and reduced autoantibody production.2
We report the case of a 63-year-old woman who presented with systemic lupus erythematosus (SLE) fulfilling the American College of Rheumatology (ACR) criteria and requiring treatment for autoimmune thrombocytopoenia, Coombs positive autoimmune haemolytic anaemia, polyarthritis and hair loss. Anti-nuclear antibody (ANA), extractable nuclear antigen (ENA) (U1 riboucleoprotein (U1RNP)) and anti-double-stranded (ds)DNA antibody tests were positive, and serum complement C3 and C4 levels were decreased (European Consensus Lupus Activity Measurement (ECLAM) score: 4.5). The patient was diagnosed as having SLE in 1998. Apart from earlier treatment with either azathioprin or methotrexate, no other immunosuppressants had been applied. At the time of first presentation to our facility (2009) the patient was treated solely with prednisolone. In 2004, the patient was diagnosed as having MM (IgG κ), which did not necessitate treatment at that point of time (stage I according to Salmon and Durie, bone marrow infiltration: 15%). At the time of the 2009 presentation, progression of the MM was revealed with a substantial increase in IgG, total serum protein and bone marrow infiltration (30%). Furthermore, new diffuse osteolytic lesions were detectable on MRI of the spine. Prednisolone medication at an initial dose of 50 mg/day was given. After her thrombocyte count increased, bortezomib was introduced at a dose of 1.5 mg on days 1, 4, 8 and 11 of each 28-day cycle. Three such cycles were applied. On this medication there was a substantial clinical improvement as well as an amelioration of several laboratory findings. The prednisolone dose was reduced to 12.5 mg/day, and the ECLAM score decreased to 2.5. Figure 1 shows the time course for the relevant parameters. Overall tolerability was good, with only one bortezomib injection skipped due to an upper airway infection. At the end of follow-up (12 months) ENA and dsDNS antibody tests were persistently negative and the patient's complement level and platelet count were normal. The patient had an ECLAM score of 2. The prednisolone dose was 5 mg/day.
In this case, a paraneoplastic genesis of SLE could be considered; however this seems unlikely as the clinical presentation was typical and first SLE manifestations preceded the detection of MM by more than 6 years. To our knowledge this is the first report of a patient with SLE and concomitant MM successfully treated with bortezomib for both conditions. Our observation indicates that bortezomib may be effective in SLE, probably due to depletion of long-lived and short-lived plasma cells. However, as bortezomib treatment is associated with substantial toxicity3 (eg, thrombocytopoenia, neuropathy) it is not likely to become a preferred option in SLE treatment. Nevertheless, there is a need for new drugs in refractory cases of life-threatening SLE and bortezomib is clearly a candidate for further clinical trials.
Competing interests None.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.