Contributions
Abstract: P1211
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: The efficacy of anti-CD20 drugs is linked to the depletion of CD20+ (and CD19+) B- lymphocytes. Conversely, increased risk of infections can be related to lowered levels of immunoglobulins and other immune cell populations. Off-label low dose rituximab (RTX) (500 or 1000 mg first dose; 500 mg every 6 months) is the most common MS treatment strategy in Sweden. However, its impact on cellular and immunoglobulin profiles has not been investigated.
Objectives and aims: To compare CD3+ (T cells), CD19+ (B cells), CD16+CD56+ (NK cells), neutrophil and monocyte counts, as well as immunoglobulin G (IgG) and M (IgM) levels at baseline and after two doses of RTX.
Methods: Patients that received RTX infusions at the Karolinska University Hospital were identified through the Swedish MS registry. Data on baseline (0-45 days before) and follow up (4-7 months after infusions) immunological parameters was extracted from medical records.
Results: We identified more than 800 patients and have performed preliminary analyses in 81 of them, where 65 had neutrophil and monocyte counts; 55 T/B/NK cell counts; 56 IgG and 12 IgM levels. Data were analyzed using repeated measures with one way ANOVA to compare baseline with outcomes after one and two doses of RTX. IgM levels and CD19+ B cell counts were lowered significantly after one or two doses of RTX. Mean differences from baseline to follow up after two doses were 0.29 g/L (0.15-0.46 95% CI; p < 0.0001) and 0.20x10^9/L (0.17-0.25 95% CI; p< 0,0001) for IgM and CD19+ B cells, respectively. After two doses of RTX 41 patients had CD19+ B cells ≥0.01 and 38 < 0.01, while IgM levels did not differ between the groups. All other differences were not significant. However, a post-hoc analysis showed an initial reduction in neutrophils after the first dose, which returned to baseline level after the second dose. One patient experienced mild neutropenia (1.3x10^9/L) after the first dose. Two patients experienced relapses 4 months after initiation of RTX and two patients had new T2 lesions.
Conclusions: Low dose RTX lowered IgM levels and B cells, with retained clinical efficacy. The effect on IgM is consistent with a reduced capacity to mount antibody responses to new infections, while stable levels of IgG suggests previously acquired humoral immunity to be intact. Further studies with larger cohorts and across different dosing regimens and different anti-CD20 drugs will be needed to generate comparative effectiveness and safety data.
Disclosure: Björn Evertsson: nothing to disclose
Katarina Fink: has received an unrestricted research grant from Biogen and served on advisory boards for Teva, Roche and Merck. KF has hold lectures for Merck and Biogen.
Anja Finn: nothing to disclose
Fredrik Piehl: has received research grants from Biogen, Novartis, and Genzyme, and fees for serving as Chair of DMC in clinical trials with Parexel.
Faiez Al Nimer: nothing to disclose
Abstract: P1211
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: The efficacy of anti-CD20 drugs is linked to the depletion of CD20+ (and CD19+) B- lymphocytes. Conversely, increased risk of infections can be related to lowered levels of immunoglobulins and other immune cell populations. Off-label low dose rituximab (RTX) (500 or 1000 mg first dose; 500 mg every 6 months) is the most common MS treatment strategy in Sweden. However, its impact on cellular and immunoglobulin profiles has not been investigated.
Objectives and aims: To compare CD3+ (T cells), CD19+ (B cells), CD16+CD56+ (NK cells), neutrophil and monocyte counts, as well as immunoglobulin G (IgG) and M (IgM) levels at baseline and after two doses of RTX.
Methods: Patients that received RTX infusions at the Karolinska University Hospital were identified through the Swedish MS registry. Data on baseline (0-45 days before) and follow up (4-7 months after infusions) immunological parameters was extracted from medical records.
Results: We identified more than 800 patients and have performed preliminary analyses in 81 of them, where 65 had neutrophil and monocyte counts; 55 T/B/NK cell counts; 56 IgG and 12 IgM levels. Data were analyzed using repeated measures with one way ANOVA to compare baseline with outcomes after one and two doses of RTX. IgM levels and CD19+ B cell counts were lowered significantly after one or two doses of RTX. Mean differences from baseline to follow up after two doses were 0.29 g/L (0.15-0.46 95% CI; p < 0.0001) and 0.20x10^9/L (0.17-0.25 95% CI; p< 0,0001) for IgM and CD19+ B cells, respectively. After two doses of RTX 41 patients had CD19+ B cells ≥0.01 and 38 < 0.01, while IgM levels did not differ between the groups. All other differences were not significant. However, a post-hoc analysis showed an initial reduction in neutrophils after the first dose, which returned to baseline level after the second dose. One patient experienced mild neutropenia (1.3x10^9/L) after the first dose. Two patients experienced relapses 4 months after initiation of RTX and two patients had new T2 lesions.
Conclusions: Low dose RTX lowered IgM levels and B cells, with retained clinical efficacy. The effect on IgM is consistent with a reduced capacity to mount antibody responses to new infections, while stable levels of IgG suggests previously acquired humoral immunity to be intact. Further studies with larger cohorts and across different dosing regimens and different anti-CD20 drugs will be needed to generate comparative effectiveness and safety data.
Disclosure: Björn Evertsson: nothing to disclose
Katarina Fink: has received an unrestricted research grant from Biogen and served on advisory boards for Teva, Roche and Merck. KF has hold lectures for Merck and Biogen.
Anja Finn: nothing to disclose
Fredrik Piehl: has received research grants from Biogen, Novartis, and Genzyme, and fees for serving as Chair of DMC in clinical trials with Parexel.
Faiez Al Nimer: nothing to disclose