Immunization to rituximab is more frequent in systemic autoimmune diseases than in rheumatoid arthritis: ofatumumab as alternative therapy

Abstract

Objectives The frequency and consequences of anti-drug antibodies to rituximab (RTX-ADA) are not well known in RA and even less in other systemic auto-immune diseases (sAID). We aimed to evaluate the frequency, consequences and predictive factors of RTX-ADA in RA and sAID. Methods All patients presenting with RA or other sAID treated with RTX from 2012 to 2017 in our tertiary reference centre for sAID were retrospectively studied. Patients who were tested for RTX-ADA were identified. Results One hundred and ninety-nine patients were treated with RTX (RA: 124, other sAID: 75). Among 62/199 (31.1%) tested for RTX-ADA, 14 were positive: 3/35 RA (8.6%) and 11/27 (40.7%) other sAID, (P = 0.0047). Among the whole RTX-treated populations, the frequency of RTX-ADA was 2.4% and 14.7% (P = 0.0026) in RA and sAID, respectively. Most of the immunized patients had infusion reactions to second or subsequent RTX cycles (11/14) and loss of efficacy (2/14). Predictive factors of immunization were sAID vs RA (78.6% vs 21.4%, P = 0.026, adjusted odds ratio (OR) = 5.35[1.43—54.75]) and African ethnicity (57.1% vs 4.2%, P < 0.001, adjusted OR = 9.25 [5.08—302.12]). Associated immunosuppressive therapy did not protect against immunization. Three patients with pSS immunized against RTX were treated with ofatumumab with complete remission of their disease. Conclusion Immunization against RTX is more frequent in other sAID than in RA. Testing for RTX-ADA must be performed in patients with infusion reactions or loss of efficacy especially if they are of African origin. Immunized patients might be treated efficiently and safely with ofatumumab. This alternative should be further evaluated for sAID.

Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy

“…S11 Humanized or fully human antibodies have shown efficacy in some autoimmune or inflammatory diseases—such as inflammatory bowel disease, rheumatoid arthritis, systemic autoimmune diseases, and chronic inflammatory demyelinating polyneuropathy—after the development of resistance to chimeric monoclonal antibodies following the appearance of antidrug antibodies. 4 , 5 , 6 Therefore, the use of obinutuzumab or ofatumumab in treatment of pMN is an attractive option. In 2 recent case series with rituximab refractory pMN, obinutuzumab has been shown to be effective.…”

First exposure to rituximab is associated to high rate of anti-drug antibodies in systemic lupus erythematosus but not in ANCA-associated vasculitis

“…In a retrospective analysis by Combier et al, having a systemic disease was a major factor associated to the presence of ADAs. The study though included only fifteen SLE patients, and five AAV, as the majority of systemic illnesses were represented by Sjögren’s syndrome [ 12 ].…”

“…In addition to the type of monoclonal antibody, the rate of occurrence of ADAs can also depend on other patient- or drug-related factors, such as the route and frequency of administration of the drug, the different dosing regimens, the presence of co-medications and the underlying disease. Indeed, some systemic inflammatory diseases appear more prone to the development of ADAs than other illnesses [ 12 ].…”

Rituximab – The first twenty years

“…At least a significant part of these infusion reactions are thought to be due to the development of anti-drug antibodies. 35 , 36 The occurrence of serum sickness type of reactions is considered to be a contraindication to re-exposure to rituximab.…”