Rituximab in clinical practice: dosage, drug adherence, Ig levels, infections, and drug antibodies

Abstract

The objective of this study is to explore the following: (1) the impact of two different initial doses and cumulative 2-year dose of rituximab (RTX) on drug adherence and predictors of adherence to treatment in rheumatoid arthritis (RA) patients in an observational clinical setting, (2) immunoglobulin levels (IgG/IgM/IgA) during repeated treatment and their relation to infections, and (3) development of anti-rituximab antibodies (ADA). All RA patients receiving RTX from January 2003 to April 2012 at the department were included. The initiating doses were 500 or 1000 mg intravenously days 1 and 15. Drug adherence was estimated using life-table. Baseline predictors of adherence to treatment were analyzed using Cox regression model. Levels of immunoglobulins were measured at treatment initiation and before retreatment. Serum levels of RTX and ADA were measured in 96 patients at 6 months using ELISA. One hundred fifty-three patients were included. Seventy-four (48%) started treatment with 500 and 79 (52%) with 1000 mg. No difference in drug adherence was seen between the different initial or cumulative RTX doses. Methotrexate (MTX) use and low DAS28 at baseline predicted better drug adherence. Ig levels decreased with repeated treatments but low levels were not associated with infections. 11/96 patients had developed ADA at 6 months. Long-term adherence to RTX in RA patient was not influenced by starting- or cumulative 2-year doses. MTX use and low DAS28 at baseline was positively associated with drug adherence. Decreasing Ig levels during treatment were not associated with risk of infections. Development of ADA may influence treatment efficacy and tolerability.

Alemtuzumab therapy changes immunoglobulin levels in peripheral blood and CSF

“…Other depleting antibodies used to treat autoimmune diseases, such as the anti-CD20 antibody rituximab, also lead to a significant decrease of blood immunoglobulin levels during therapy. 29 However, several studies on patients with rheumatoid arthritis (RA) treated with rituximab could demonstrate that patients with below normal immunoglobulin levels did not have more serious infections than patients with normal immunoglobulin levels. [29][30][31][32] Our results appear to be in contrast to the findings of McCarthy et al 33 who performed a pilot study regarding immunologic memory to common viruses and responses to vaccinations in 24 patients with prior alemtuzumab treatment.…”

Long‐term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: Results at 5 years from the French prospective registry ITP‐ritux

“…This incidence rate is in the lower range of the severe infections rate observed in other autoimmune diseases treated with rituximab and particularly in large cohorts of patients with RA (1.5-7.9/100 patient-years). 17,[25][26][27][28][29][30] Chronic ITP could be associated itself with an increased risk of serious infections, with an SIR of 8.74 (95% CI, 7.47-10.18). 31 So, the relation between the incidence of severe infections we observed and the use of rituximab is questionable, because most of our patients with severe infection had comorbidities or received prolonged treatment with steroids or immu- depletion secondary to the use of rituximab, it is not a surprise that the incidence of severe infections we observed was higher during the first year, when B-cell depression induced by rituximab is substantial, with one third of infections seen.…”

“…3.2.6 | Hypogammaglobulinemia and neutropeniaGammaglobulin level was not systematically monitored. Among the 142 (52%) patients with available data, five with median age 49 years[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] showed profound hypogammaglobulinemia (<5 g/L) after a median of 25[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] months after the last rituximab infusion. The median lowest gammaglobulin level in these five patients was 3.12…”

Late-onset hypogammaglobulinemia after rituximab therapy

“…Во многих исследованиях показано, что риск развития гипогаммаглобулинемии увеличивается при неоднократных курсах ритуксимаба, предшествующей терапии циклофосфамидом или метотрексатом, изначально сниженном содержании Ig [6,12,14,30,[32][33][34][35]. В то же время, Marco и соавт.…”

“…Наряду с исследованиями, в которых установлено, что наличие и степень гипогаммаглобулинемии после терапии ритуксимабом коррелирует с риском и тяжестью инфекционного синдрома [13, 14, 40], есть и сообщения об отсутствии такой взаимосвязи [18,20,27,30,35].…”