Immunoglobulin Level Changes in Patients with Multiple Sclerosis Treated with Anti-CD20 Monoclonal Antibodies
Brandi Vollmer1, Timber Bourassa1, Erin Marsh1, Vi Dao1, Abhijit Gadkari2, Brandon Brown2, Stefan Sillau1, Kavita Nair1, Enrique Alvarez1
1University of Colorado, 2Novartis
Objective:
To examine immunoglobulin G(IgG) and immunoglobulin M(IgM) changes while on anti-CD20 treatment for multiple sclerosis(MS).
Background:
Ocrelizumab(OCR), rituximab(RTX), and ofatumumab(OFA) are B-cell depleting therapies used in MS. A decrease in IgG concentration associated with B cell depletion may pose an increased risk of infection.
Design/Methods:
Anti-CD20 naïve MS patients starting OCR (n=118), RTX(n=140), or OFA(n=68) at the Rocky Mountain MS Center, University of Colorado after January 2017 and at least one IgG value pre- and post-initiating therapy were retrospectively followed. Lab data, disease history, and patient characteristics were collected. Descriptive statistics and longitudinal regression models were used to examine patient characteristics and IgG and IgM changes over time.
Results:
OCR, RTX, and OFA patients had a mean age of 42.81, 42.92, and 40.74 years at treatment initiation; had a mean MS disease duration of 7.53, 6.17, and 4.03 years, respectively; and were predominantly female(OCR:69.49%; RTX:68.57%; OFA:80.88%). Mean time on therapy for OCR, RTX and OFA was 44.94, 40.19, and 16.17 months, respectively. Geometric mean baseline IgG values were 957.71(95% CI:922.24, 994.54), 940.34(95% CI:901.80, 980.53) and 978.56(95% CI:912.07, 1049.90) mg/dl for OCR, RTX, and OFA respectively. Few patients developed IgG levels below 500 mg/dl (OCR:5.93%; RTX:5.71%; OFA:0.00%). The estimated IgG annual changes were -2.93%(95% CI:-4.30%,-1.55%, p<0.0001), -1.81% (95% CI:-2.88%,-0.73%, p=0.0011), and -2.63%(95% CI:-7.27%,2.24%, p=0.2829), for OCR, RTX, and OFA respectively. Geometric mean baseline IgM values were 101.90(95% CI:92.32, 112.47), 101.11(95% CI:91.68, 111.51) and 104.01(95% CI:89.58, 120.77) for OCR, RTX and OFA, respectively. Few patients developed IgM levels below 25 mg/dl (OCR:15.38%; RTX:10.95%; OFA:6.25%). The estimated IgM annual changes were -17.82%(95% CI:-20.34,-15.23, p<0.0001), -19.00%(95% CI:-21.42,-16.52, p<0.0001), and -27.90%(95% CI:-35.02,-20.00, p<0.0001), for OCR, RTX, and OFA respectively.
Conclusions:
Findings suggest a reduction in IgG and IgM values over time on B-cell depletion. Additional follow-up is needed to assess comparisons between therapies.