RITUXIMAB IN IGG4-RD: AN OPEN-LABEL NON-RANDOMIZED OBSERVATIONAL STUDY

BackgroundIgG4-related disease (IgG4-RD) is a rare, heterogenous and potentially severe disease. An open-label trial demonstrated efficacy of rituximab (RTX) in IgG4-RD [1]. Recently, four distinct phenotypes of IgG4-RD were identified [2]. There is a paucity of studies investigating RTX efficacy across these phenotypes.ObjectivesInvestigate efficacy and safety of RTX in IgG4-RD and segregated by phenotypes.MethodsThis is an open-label non-randomized single center observational study. All patients with IgG4-RD (diagnosed by expert opinion) at the Oslo University Hospital treated with ≥ 1 dose of RTX with 12 months follow-up were included. Two experts (JV, ØMi) assigned patients to phenotypes. Glucocorticoid (GC) treatment was allowed. We measured disease activity by the IgG4-RD Responder Index (IgG4-RD RI) at baseline, 6 months, and 12 months. We defined a composite primary outcome consisting of two measures; (i) reduced disease activity (i.e., ≥2 points improvement in IgG4-RD RI from baseline and/or IgG4-RD RI score 0 at follow-up), and (ii) no disease flares (i.e., no ≥2 points worsening of IgG4-RD RI and no need to increase GC dose) at 6 months. Secondary outcomes were (a) reduced disease activity at months 6 or 12, (b) remission (IgG4-RD RI score 0 and GC dose ≤ 7.5 mg) at 6 or 12 months and (c) safety. Descriptive statistics were applied.ResultsWe included 40 patients, of which 30 (75%) were male and 35 (88%) Caucasian. Mean age and disease duration at time of first RTX infusion was 58 and 3 years, respectively. Seventeen of the 40 patients (43%) received RTX as add-on therapy (following GC for > 3 months), while 13 (33%) received RTX as upfront combination therapy with GC, and 10 (25%) received RTX as upfront monotherapy. All 40 patients received an infusion of 1000 mg RTX at study baseline (dose 1A at week 0) and 39 of these 40 patients (98%) received a second RTX infusion (dose 1B) at week 2. Additional infusions of 500-1000 mg RTX were administered at weeks 26 (dose 2A) and 28 (dose 2B) in 24 (60%) and 7 (18%) patients, respectively. The composite primary endpoint was met by 31/40 patients (78%). Reduced disease activity at 6 and 12 months were seen in 34 (87%) and 35 (90%) patients, respectively. Fifteen patients (38%) were in remission at 6 months, and 22 (56%) were in remission at 12 months. “Retroperitoneum and Aorta” showed lowest response rates, while “Head and Neck-Limited” had the highest rate of flares (Table 1). Mild infusion reaction occurred in 8 (20%) patients. Hypogammaglobulinemia was observed in 4 (10%). Infection requiring hospitalization occurred in 6 (15%), including one fatal infection which was the only death in the study period.Table 1.All40 (100)Pancreato-Hepato-Biliary9 (23)Retroperitoneum and Aorta 6* (15)Head and Neck-Limited 14 (35)Mikulicz and Systemic 11 (28)Baseline (n=40)Male, n (%)30 (75)8 (89)5 (83)8 (57)9 (82)Caucasian (%)35 (88)9 (100)6 (100)12 (86)8 (73)Age, years (SD)58 (14)63 (9)66 (3)49 (18)60 (11)Disease duration, years (SD)3 (4)4 (3)3 (4)2 (2)5 (6)2019 ACR/EULAR classification criteria (%)28 (70)8 (89)3 (50)6 (43)11 (100)IgG4-RD RI at diagnosis (SD)10 (6)10 (5)7 (4)7 (3)17 (4)IgG4-RD RI at RTX 1A, (SD)8 (6)9 (4)5 (4)6 (4)12 (7)6 months (n=39)*IgG4-RD RI (SD)2 (2)3 (3)2 (2)1 (1)1 (2)Primary outcome, n (%) (n=40)31 (78)9 (100)3 (50)9 (64)10 (91)Reduced disease activity, n (%)34 (87)9 (100)3 (60)12 (86)10 (91)Remission, n (%)15 (38)4 (44)06 (43)5 (46)Flare, n (%)3 (8)003 (21)012 months (n=39)*IgG4-RD RI (SD)1 (1)1 (1)0 (1)1 (1)1 (2)Reduced disease activity, n (%)35 (90)9 (100)4 (80)12 (86)10 (91)Remission, n (%)22 (56)7 (78)3 (60)7 (50)5 (45)Flare, n (%)4 (10)1 (11)1 (20)2 (14)0*One patient died shortly after 1A, and is not included in secondary efficacy outcomesConclusionIn our observational study, RTX appears safe and effective in IgG4-RD, with the highest response in patients with Pancreato-Hepato-Biliary phenotype. Relatively low remission rates across all phenotypes indicate an unmet need for improved treatment.References[1]Carruthers MN et al. Ann Rheum Dis. 2015;74(6):1171-1177.[2]Wallace ZS et al. Ann Rheum Dis. 2019;78(3):406-412.Disclosure of InterestsJens Vikse Speakers bureau: Novartis, Consultant of: Novartis, Jupiter Life Science Consulting, Øyvind Midtvedt: None declared, Øyvind Molberg: None declared, Bjørg Tilde Svanes Fevang: None declared, Øyvind Palm: None declared, Torhild Garen: None declared, Katrine Brække Norheim: None declared, Gunnstein Bakland: None declared, Marianne Wallenius: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim