Serum immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term maintenance therapy with rituximab in patients with granulomatosis with polyangiitis.
OBJECTIVE
Rituximab (RTX) is a B cell depleting agent used to induce and maintain remission in patients with granulomatosis with polyangiitis (GPA). As the development of hypogammaglobulinaemia in GPA patients on long-term RTX has not been addressed, the aim of this study was to investigate changes in immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term RTX maintenance therapy in GPA.


METHODS
We used a single-centre cohort study of 29 GPA patients who received a median total cumulative dose of CYC of 17 g and were treated with 2 g RTX followed by re-treatment with either 2 g once annually, 1 g biannually or a combination of both. Ig levels were measured before each RTX re-treatment and hypogammaglobulinaemia was defined as levels of total immunoglobulin <6 g/l.


RESULTS
During a median follow-up of 4 years, patients received a cumulative dose of 9 g RTX. While serum Ig levels decreased during RTX maintenance, the largest decrease occurred after the first infusion. Baseline Ig levels and the CYC cumulative dose predicted Ig levels, whereas the RTX cumulative dose did not. Eight patients (28%) discontinued RTX due to hypogammaglobulinaemia. Male gender [hazard ratio (HR) = 8.7, P = 0.044], kidney involvement (HR = 6.5, P = 0.083) and the 1 g biannual regimen (HR = 8.0, P = 0.024) increased the risk to discontinue RTX due to hypogammaglobulinaemia, whereas orbital-subglottic involvement (HR = 0.23, P = 0.080) decreased it.


CONCLUSIONS
Hypogammaglobulinaemia occurred in one-quarter of GPA patients during RTX maintenance, independent of the RTX cumulative dose. Male gender, kidney involvement and the 1 g biannual RTX regimen constitute risk factors for severe hypogammaglobulinaemia necessitating withdrawal of RTX.
Bone and Joint Research Group, Institute of Clinical Medicine, University of Tromsø, Rheumatology Department, University Hospital of North Norway, Tromsø, Norway and Division of Medicine, Royal Darwin Hospital, Department of Health, Darwin, NT, Australia. emilio.besada@unn.no.
Emilio
E
Besada
Bone and Joint Research Group, Institute of Clinical Medicine, University of Tromsø, Rheumatology Department, University Hospital of North Norway, Tromsø, Norway and Division of Medicine, Royal Darwin Hospital, Department of Health, Darwin, NT, Australia.
Wenche
W
Koldingsnes
Bone and Joint Research Group, Institute of Clinical Medicine, University of Tromsø, Rheumatology Department, University Hospital of North Norway, Tromsø, Norway and Division of Medicine, Royal Darwin Hospital, Department of Health, Darwin, NT, Australia. Bone and Joint Research Group, Institute of Clinical Medicine, University of Tromsø, Rheumatology Department, University Hospital of North Norway, Tromsø, Norway and Division of Medicine, Royal Darwin Hospital, Department of Health, Darwin, NT, Australia.
Johannes C
JC
Nossent
D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000139:chemically induced*; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012042:Registries; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; D007136:Immunoglobulins; D007155:Immunologic Factors; D000069283:Rituximab
ANCA-associated vasculitis; B cell; Hypogammaglobulinaemia; granulomatosis with polyangiitis; immunoglobulins; maintenance; rituximab; safety