Background Biological therapies such as rituximab are increasingly employed for the treatment of rheumatoid arthritis (RA). By binding to the CD20 cell surface antigen, rituximab induces apoptosis and complement-mediated lysis of the B cell population. This population is estimated to recover within 3 to 12 months. With the reduction in B cell numbers, immunoglobulin levels also fall, but are expected to recover in the same timescale as the B cell pool. Evidence however suggests that hypogammaglobulinaemia can progress with successive treatment cycles.
This is a concern in already immunocompromised RA patients, as infection is one of the commonest causes of mortality in RA. An international consensus in May 2010 advised that immunoglobulin levels are checked at baseline and prior to each rituximab infusion in the treatment of RA.
Objectives A clinical audit was undertaken at the University Hospitals of Leicester (UHL) NHS Trust in order to monitor compliance with the forementioned standards and to determine whether or not immunoglobulin levels were being monitored adequately and if they fell with successive infusions.
Methods The Rheumatology Department database of all RA patients who had received one or more cycles of rituximab was validated by cross-referencing with pharmacy records. The laboratory database was subsequently cross-examined to establish whether immunoglobulin levels had been checked prior to each infusion cycle, and the values of IgG, IgA and IgM were documented.
Results 133 patients had received one or more cycles of rituximab (female to male ratio of 3:1, mean disease duration 14 years). Eighty (60%) patients had seropositive RA.
82 patients received two cycles, 46 three cycles, 19 four cycles and 4 patients five cycles of rituximab. 122 patients (92%) had their immunoglobulin levels checked prior to the first rituximab infusion, 78 (95%) before the second infusion, 44 (96%) prior to the third infusion and 18 (95%) before the fourth infusion. Of those who had 5 cycles of rituximab, 3 (75%) had their immunoglobulin levels checked before each treatment. The average compliance with international standards was therefore 91%. IgG levels fell from a mean of 12.7g/l prior to cycle one, to 10.6g/l prior to cycle five. IgA levels fell from 3.3g/l to 2.6g/l. IgM levels fell the greatest proportionately from 1.5g/l to 0.8g/l prior to cycle five.
3 patients had IgG levels below the reference range at baseline. Of those, 1 patient went on to receive 2 infusions of Rituximab. 3 more patients had low IgG levels prior to the second infusion.
Conclusions Immunoglobulin monitoring at UHL is compliant with international standards. We have also confirmed that within our cohort of RA patients immunoglobulin levels fell with successive rituximab infusions. This reduction was most marked in the IgM subset, in keeping with trends previously noted in clinical trials. In our cohort, we did not find any increase in serious infections among patients with Ig levels below the reference ranges. However, further audit is required to identify the long-term sequele of persistent iatrogenic hypogammaglobulinaemia.
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Disclosure of Interest None Declared
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