relationship between t lymphocytes depletion and clinical response to rituximab in rheumatoid arthritis (lyritux)

Conditions: Rheumatoid Arthritis

Summary: rituximab, an anti cd-20 monoclonal antibody targeting b lymphocytes is prescribed in rheumatoid arthritis (ra) patients refractory to tnf alpha antagonists. according to previous studies, 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24. in a recent retrospective study, a cd4+ t-lymphocytes depletion was observed after a first course of rituximab in ra patients. the absolute cd4+ number at week 12 was 37% (±33) of the baseline value, leading to \< 200 cells/µl in 5% of patients. interestingly the absence of cd4+ t-lymphocytes depletion was observed in clinical non-responders, suggesting the involvement of t-lymphocytes in the mechanism of action of rituximab. so far no prospective study have supported the usefulness of lymphocyte phenotyping, in particular t-lymphocytes, to monitor rituximab-treated ra patients.

rituximab, an anti cd-20 monoclonal antibody targeting b lymphocytes is prescribed in rheumatoid arthritis (ra) patients refractory to tnf alpha antagonists. according to previous studies, (edwards, szczepanski et al. 2004; cohen, emery et al. 2006; emery, fleischmann et al. 2006) 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24. in the pathogenesis of ra, b and t lymphocytes are tightly linked through the apc fonction and cytokines production of b lymphocytes. at present, a white blood cells count is recommended in routine every 3 months in patients receiving rituximab, since cases of neutropenia have been observed in approximately 8% of patients with lymphoma after treatment. in ra patients, b lymphocytes count before each rituximab course should be done to prevent opportunistic infections (pham, fautrel et al. 2008). in a recent retrospective study, a cd4+ t-lymphocytes depletion was observed after a first course of rituximab in ra patients. the absolute cd4+ number at week 12 was 37% (±33) of the baseline value, leading to \< 200 cells/µl in 5% of patients. interestingly the absence of cd4+ t-lymphocytes depletion was observed in clinical non-responders, suggesting the involvement of t-lymphocytes in the mechanism of action of rituximab (mélet, mulleman et al. 2013). moreover, few case reports of ra patients developing opportunist infections in conjunction with cd4+ t-lymphocyte depletion have been published (teichmann, woenckhaus et al. 2008; clifford, ances et al. 2011). so far no prospective study have supported the usefulness of lymphocyte phenotyping, in particular t-lymphocytes, to monitor rituximab-treated ra patients.

Eligibility criteria:
inclusion criteria: * ra according to the american college of rheumatology (acr) criteria * treatment with adalimumab in accordance to the spc * disease modifying anti rheumatic drugs (dmards) stable 4 weeks before enrollment and during 16 weeks. * signed consent exclusion criteria: * no anti tnf-alpha failure or contraindication * previous adalimumab treatment * contraindication to adalimumab, methylprednisolone or methotrexate (when used in combination with adalimumab) * methotrexate-naive patient * any hematologic disease affecting the lymphocytes (in particular lymphomas) * any osteo-articular disease which could interfere with the interpretation of the influence of the rituximab on ra

Keywords: rheumatoid arthritis t lymphocytes rituximab