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. 2017 May;69(5):1045-1053.
doi: 10.1002/art.40032. Epub 2017 Mar 31.

Effect of Continuous B Cell Depletion With Rituximab on Pathogenic Autoantibodies and Total IgG Levels in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Frank B Cortazar  1 , William F Pendergraft 3rd  2 , Julia Wenger  2 , Charles T Owens  3 , Karen Laliberte  1 , John L Niles  1
Affiliations

Effect of Continuous B Cell Depletion With Rituximab on Pathogenic Autoantibodies and Total IgG Levels in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Frank B Cortazar et al. Arthritis Rheumatol. 2017 May.

Abstract

Objective: To evaluate the effect of rituximab on pathogenic autoantibodies and total Ig levels, and to identify serious adverse events in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with continuous B cell depletion.

Methods: We conducted a retrospective analysis of 239 patients with AAV treated with rituximab-induced continuous B cell depletion. Two treatment cohorts were analyzed: an induction group (n = 52) and a maintenance group (n = 237). Changes in ANCA titers and total Ig levels over time were evaluated using mixed-effects models. Risk factors for serious infections during maintenance treatment were evaluated using Poisson regression.

Results: During induction, IgG levels fell at a mean rate of 6% per month (95% confidence interval [95% CI] 4, 8%), while ANCA levels declined at a mean rate of 47% per month (95% CI 42, 52%) and 48% per month (95% CI 42, 54%) for patients with antimyeloperoxidase (anti-MPO) antibodies and those with anti-proteinase 3 (anti-PR3) antibodies, respectively. During maintenance treatment, with a median duration of 2.4 years (interquartile range 1.5, 4.0 years), IgG levels declined a mean of 0.6% per year (95% CI -0.2, 1.4%). New significant hypogammaglobulinemia (IgG level of <400 mg/dl) during maintenance treatment occurred in 4.6% of the patients, all of whom were in the lowest baseline IgG quartile. Serious infections during maintenance therapy occurred at a rate of 0.85 per 10 patient-years (95% CI 0.66, 1.1) and were independently associated with an IgG level of <400 mg/dl.

Conclusion: B cell-targeted therapy causes a preferential decline in ANCA titers relative to total IgG levels. Despite prolonged maintenance therapy with rituximab, IgG levels remain essentially constant. Serious infections were rare.

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Figures

Figure 1
Figure 1. Composition of induction and maintenance groups
The induction group was comprised of 52 patients who received treatment with combination rituximab, cyclophosphamide, and prednisone, and had baseline and follow up ANCA titers and IgG levels. The maintenance group was comprised of 237 patients who achieved remission after induction therapy or were transitioned from an alternative maintenance regimen.
Figure 2
Figure 2. Change in immunoglobulin levels and ANCA titers with treatment
Shown are data from linear mixed-effects models examining the percent change in ANCA titers and immunoglobulin levels over time during induction (panel A) and maintenance (panel B) therapy. Slopes with accompanying 95% confidence intervals are shown in Table 2.
Figure 3
Figure 3. Kaplan-Meier estimate of significant hypogammaglobulinemia in the maintenance group
Shown are Kaplan-Meier curves for the top 3 IgG quartiles (range 560-1657 mg/dL) compared to the lowest IgG quartile (range 408-559) in patients who entered maintenance therapy with an IgG level > 400 mg/dL. Significant hypogammaglobulinemia was defined as an IgG level < 400 mg/dL. Abbreviations: w/o, without
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References

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