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

Clin Rheumatol. 2017 Dec;36(12):2743-2750. doi: 10.1007/s10067-017-3848-6. Epub 2017 Oct 4.

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.

Keywords: Adherence to treatment; Anti-rituximab antibodies; Immunoglobulins; Rheumatoid arthritis; Rituximab.

MeSH terms

  • Antibodies / blood
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunoglobulins / blood*
  • Infections / etiology*
  • Male
  • Medication Adherence*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Rheumatic Fever / blood
  • Rheumatic Fever / drug therapy*
  • Rheumatic Fever / immunology
  • Rituximab / administration & dosage
  • Rituximab / adverse effects
  • Rituximab / immunology
  • Rituximab / therapeutic use*
  • Treatment Outcome

Substances

  • Antibodies
  • Antirheumatic Agents
  • Immunoglobulins
  • Rituximab
  • Methotrexate