Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control.

Abstract

To evaluate long-term effects on gamma-globulins and autoantibodies of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients. Eighteen RA patients undergoing abatacept (ABA-RA) and 18 age/sex-matched patients treated with TNFi (TNFi-RA) were compared regarding clinical data, total gamma-globulins (TGG), specific subtypes (IgG, IgM, IgA), free light chains (FLC), IgM/IgG rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP3), and anti-mutated citrullinated vimentin (anti-MCV), assessed before and every 6months, up to 24months. previous abatacept/rituximab or low TGG (< 0.7g/dL). At baseline, female sex (78 vs. 78%), age (55 vs. 53years), DAS28 (5.73 vs. 5.67), TGG (1.4 vs. 1.35g/dL), IgG (1168 vs. 1079mg/dL), IgM (107 vs. 113mg/dL), IgA (333 vs. 322mg/dL), kappa (342 vs. 249mg/dL), lambda (170 vs. 150mg/dL), IgM-RF (76 vs. 53UI), IgG-RF (63 vs. 25UI), anti-CCP3 (216 vs. 189UI), and anti-MCV (202 vs. 102UI) were comparable in ABA-RA and TNFi-RA (p > 0.05). Similar disease activity improvement was observed in both groups. In ABA-RA, significant decreases (p < 0.05) were observed in TGG (1.4 vs. 1.05g/dL), IgG (1168 vs. 997), IgA (333 vs. 278mg/dL), kappa (342 vs. 257mg/dL), lambda (170 vs. 144mg/dL), IgM-RF (76 vs. 37UI), IgG-RF (65 vs. 24UI), anti-CCP3 (216 vs. 183UI), and anti-MCV (202 vs. 60UI) at 6months, without further decreases. In contrast, TNFi-RA showed no decrease in any of such parameters. ABA-RA also had more often transient IgG levels under the lower limit of normality (66.7% vs. 33.3%, p = 0.046). No severe infection occurred. DAS28, ESR, and CRP correlated significantly to gamma-globulins and FLC at baseline (p < 0.05), but these correlations were longitudinally lost in ABA-RA, but not in TNFi-RA. ABA, but not TNFi, induces a safe, persistent, long-term, and non-progressive reduction in gamma-globulins and autoantibodies, including anti-MCV. This pattern is dissociated from disease activity control.Key Points• ABA induces a long-term and non-progressive reduction in gamma-globulins and FLC, which occurs regardless of disease activity control.• ABA-induced reduction in gamma-globulins and FLC promotes a dissociation of such parameters and disease activity.• The same pattern of reduction is observed in autoantibodies: IgM-RF, IgG-RF, anti-CCP3, and anti-MCV.• Low transient IgG can be observed in RA patients treated with ABA, but does not correlate to infection.