What pre‑treatment evaluations, laboratory tests, infection screenings, vaccination requirements, and contraindications should be assessed before initiating rituximab (Rituxan) in a rheumatoid arthritis patient who has had an inadequate response to at least one conventional disease‑modifying antirheumatic drug (DMARD) and, if applicable, has failed or is intolerant to a tumor necrosis factor (TNF) inhibitor?

Pre-Treatment Evaluations Before Starting Rituximab for Rheumatoid Arthritis

Before initiating rituximab in an RA patient who has failed at least one conventional DMARD and (if applicable) a TNF inhibitor, you must screen for hepatitis B (including core antibody and surface antigen), obtain baseline immunoglobulin levels, ensure tuberculosis screening is current, update vaccinations (especially herpes zoster), and confirm adequate B-cell and immune function. 1, 2

Mandatory Infection Screening

Hepatitis B Evaluation

• Prophylactic antiviral therapy is strongly recommended over monitoring alone for patients initiating rituximab who are hepatitis B core antibody positive, regardless of surface antigen status. 1
• Screen all patients for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) before rituximab initiation. 2
• Reactivation of occult hepatitis B infection has been reported in RA patients receiving rituximab, making this screening particularly critical in Asian countries where hepatitis B prevalence is high. 2

Tuberculosis Screening

• Screening for tuberculosis is strongly recommended before starting rituximab, consistent with requirements for all biologic DMARDs. 1
• Obtain either tuberculin skin test (TST) or interferon-gamma release assay (IGRA) such as QuantiFERON-TB Gold. 3

Required Laboratory Tests

Baseline Immunologic Assessment

• Measure baseline serum immunoglobulin levels (IgG, IgM, IgA) before rituximab initiation, as repeated treatment is associated with hypogammaglobulinemia that may increase infection risk. 2
• Obtain complete blood count with differential to establish baseline B-cell counts and rule out cytopenias. 4

Standard Pre-DMARD Laboratory Panel

• Complete blood count with differential 4
• Hepatic function tests (AST, ALT, alkaline phosphatase, bilirubin) 4
• Renal function (serum creatinine, estimated GFR) 4
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to document baseline disease activity 4

Vaccination Requirements

Pre-Treatment Immunizations

• Administer age-appropriate vaccines, including herpes zoster vaccine, before initiating rituximab therapy. 1
• Complete all indicated vaccinations at least 2–4 weeks before rituximab infusion, as B-cell depletion will interfere with vaccine response. 2
• Live vaccines are contraindicated once rituximab therapy begins and should be given beforehand if needed. 2

Contraindications and Special Populations

Absolute Contraindications

• Active serious infection requiring intravenous antibiotics or hospitalization is a contraindication to rituximab initiation. 1
• Severe, uncontrolled infections must be resolved before starting therapy. 2

Relative Contraindications and Cautions

• Patients with persistent hypogammaglobulinemia without infection may continue rituximab, but those with baseline low immunoglobulin levels require careful risk-benefit assessment. 1
• Progressive multifocal leukoencephalopathy (PML), though rare, has been linked to rituximab use and must be discussed with patients. 2

Preferred Patient Population

• Rituximab is conditionally recommended over other DMARDs for patients with a previous lymphoproliferative disorder for which rituximab is an approved treatment. 1
• Seropositivity (rheumatoid factor or anti-CCP positive), complete B-cell depletion shortly after treatment, and previous failure to no more than one anti-TNF agent are associated with greater clinical benefits. 2

Clinical Assessment Requirements

Disease Activity Documentation

• Document current disease activity using validated measures (DAS28, SDAI, or CDAI) to establish baseline and justify biologic therapy. 1
• Confirm moderate-to-high disease activity despite adequate trial of at least one conventional DMARD (typically methotrexate at 20–25 mg weekly for ≥3 months). 1, 4
• For patients being considered for rituximab, document inadequate response to at least one TNF inhibitor, as this is required for FDA approval. 1

Baseline Functional Assessment

• Obtain Health Assessment Questionnaire Disability Index (HAQ-DI) score to document baseline functional status. 5
• Document tender and swollen joint counts (28-joint assessment minimum). 4

Common Pitfalls to Avoid

• Do not initiate rituximab without hepatitis B screening—reactivation can be fatal and prophylactic antiviral therapy is strongly recommended for core antibody–positive patients. 1, 2
• Do not skip baseline immunoglobulin measurement—you need this to monitor for progressive hypogammaglobulinemia with repeated courses, which increases serious infection risk. 2
• Do not use rituximab as first-line biologic therapy unless the patient has a lymphoproliferative disorder for which rituximab is indicated; FDA approval requires inadequate response to TNF inhibitors first. 1
• Do not administer live vaccines after rituximab initiation—complete all vaccinations before starting therapy. 2
• Do not overlook occult hepatitis B infection (isolated anti-HBc positive)—these patients still require prophylactic antiviral therapy when starting rituximab. 1