Background Immunoglobulins (Ig) and immune complexes generate and fine-tune inflammation in rheumatoid arthritis (RA) by interacting with receptors on immune cells. After successful antirheumatic treatments, reductions of Igs are observed in many patients. Rituximab (RTX), a second line biologic anti-rheumatic drug, has proven efficacy in RA; by interacting with CD20, it causes lysis/apoptosis of B-cells. However, this may increase the patients` infection sensitivity and reduce their immune response to vaccines. Consequently, there is lack of information on the optimum level of B-cell depletion (and biomarkers thereof), and on rheumatics' exposure to infections in everyday clinical practice.
Objectives To evaluate if the degree of RTX-mediated B-cell depletion in seropositive RA is correlated to joint disease activity and Ig serum levels. To review the extent, the nature, and risk factors of infectious diseases during RTX treatment in a non-selected RA cohort.
Methods Sixty-nine patients (57 female/12 men, mean age 58.7 years) treated with at least one course of RTX at the Department of Rheumatology, University Hospital in Uppsala were included. A high proportion (71%) had erosive disease, 72% were on DMARD and 60% on steroid treatment. On average 1.2 other biologics had been tested prior to RTX. Analyses of Ig isotypes, IgG subclasses and IgM RF, and joint disease activity were evaluated just before the next RTX course was administered. Data were collected from medical records regarding occasions with leuco-/neutropenia, medications for concurrent diseases, admissions due to various infections, and the number of systemic or topical antibiotics prescribed.
Results RA patients who were RF- at evaluation had acquired a higher total dose of RTX, had lower disease activity and lower serum IgA than RF+ patients. No difference in the number of infections or prescribed antibiotics was observed comparing RF+ with RF- patients. The total IgM levels correlated positively with the SJC and the IgG3 serum levels and negatively with the RTX total dosis. The HAQ score was negatively related to the IgG1 serum levels. In 4 patients transient leuco-/neutropenia was observed; one of these was administered to hospital and was successfully treated for pneumonia. In the medical records, 244 systemic (1.21 per patient year) and 33 topical (0.20 per patient year) antibiotic prescriptions were observed; the most common infections were of airways (n=147), urinary tract (n=87), and skin (n=49). One case of hepatitis B reactivation was observed in a patient who voluntarily had paused prophylactic antiviral treatment. A total of 10 in-patient admissions was observed, and one death occurred due to tick borne virus encephalitis (TBE). At encephalitis onset this patient had no detectable levels of anti-TBE antibodies although she had been immunized according to guidelines. RA patients with concurrent treatments for diseases with increased risk of developing infections had more infections and antibiotic therapies than non-risk patients.
Conclusions A good response to RTX-treatment is followed by conversion to seronegativity in initially RF+ individuals. During RTX treatment, an increased risk of infections is seen especially in RA patients with concomitant diseases. These patients should be recommended to review their vaccination-status, to optimize their non-RA treatments, and to seek medical care in case of infection symptoms. In endemic areas TBE vaccination before RTX start should be mandatory.
Disclosure of Interest None declared
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