Table 3

Rituximab treatment risks and management. Unless a separate reference is given, information is adapted from MabThera SmPC [56], experience from RA

RiskDescriptionRecommended management
Infusion reactionsThe highest risk is with the first infusion (~30%).
Most reactions are mild (headache, pruritus, throat irritation, flushing, rash, urticaria, fever, hypo/hypertension).
Severe or life-threatening anaphylactoid infusion reactions leading to drug discontinuation are uncommon (<1/100 cases).
Pretreatment with corticosteroids reduces the frequency and severity of reactions.
If possible, withhold antihypertensive medications on the morning of the infusion.
Adhere to manufacturers’ advice regarding infusion rates.
Unless contraindicated, give intravenous methylprednisolone 100 mg before the infusion.
Manage mild reactions with interruption or slowing of infusion, paracetamol and antihistamine. Restart infusion at a reduced rate once symptoms resolve. Manage severe reactions as per the Advanced Life Support algorithm. Have necessary equipment and medications available.
Mucocutaneous reactionsSevere skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis occur very rarely following rituximab infusion, some with fatal outcome (<1/10 000 cases).Do not re-treat with rituximab if the patients develops a severe skin reaction.
Adverse cardiac eventsRituximab is not directly cardiotoxic but angina pectoris, arrhythmias and heart failure rarely occur (<1/1000 cases).Consider alternative treatment options in patients with severe uncontrolled cardiac disease. Manufacturers recommend ‘close monitoring’ of those with known cardiac disease.
InfectionsMost infections are mild to moderate, consisting of upper respiratory tract and urinary tract infections (very common, >1/10 cases). Bronchitis, sinusitis and gastroenteritis occur in 1/100-1/10 cases. Serious opportunistic infections are rare, including reactivation of hepatitis B. Hypogammaglobulinaemia and neutropenia may contribute to infection risk in some cases (see below).Do not give rituximab to patients with active infection. Ask and counsel patients regarding infection or risk of infection.
We recommend annual influenza vaccine and five-yearly pneumococcal vaccine throughout treatment.
See notes in table 2 regarding specific infectious risks: hepatitis B, C and tuberculosis.
Secondary antibody deficiencyDecreased IgM levels are very common; decreased IgG levels are common.
Hypogammaglobulinaemia seems to be time and dose dependent.78 79 Prior exposure to immunosuppressant drugs may be an additional risk factor.81 88 Patients with low IgG are at risk of infection, particularly recurrent bacterial sinopulmonary infections, but risk does not correlate directly with IgG level.78 81 Patients with low baseline IgG levels are at particular risk of infection.80
Check baseline total serum immunoglobulin levels prior to starting rituximab. Be aware of higher infection risk in patients with low IgG and consider alternative options.
Recheck serum Ig in the context of severe or recurrent infections. See Box 1 for approach to symptomatic secondary antibody deficiency.
Consider checking IgG levels in patients with a history of immunosuppressive medication use before retreatment with rituximab.
NeutropeniaMay occur after first or subsequent infusions. The highest risk is 3–6 months after infusion. Prevalence of 1.3%–2.3% when rituximab is given for autoimmune indications101; reported in MS and NMOSD.102–104
The severity and duration of neutropenia is unpredictable. Many cases are asymptomatic and self-limiting but grade IV neutropenia (<0.5/109/L) with severe infection is rarely reported.
Check full blood count prior to administering rituximab and on symptoms or signs of infection.
Observe cases of asymptomatic mild neutropenia. G-CSF has been used to hasten recovery in grade IV neutropenia or sepsis.104
Though it may recur, neutropenia is not a contraindication to ongoing rituximab therapy—several case series support ongoing use in autoimmune disease.101 103–105
PMLRituximab may increase risk of PML in individuals already at risk due to pre-existing conditions or immunosuppression. Risk is estimated at 1 in 30 000 cases exposed to rituximab.106 No cases have yet been described when rituximab is used alone to treat neuroinflammatory disease.Discuss progressive multifocal leucoencephalopathy risk during consent process.
JCV antibody titres do not have an established role in rituximab use.
MRI if suggestive clinical features develop.
PRESDescribed following rituximab administration in NMOSD and non-neurological indications. Prevalence of 0.5% in a large cohort of patients with NMOSD.13MRI if suggestive clinical features develop.
MalignancyNo increased risk identified.
  • Italicisedpoints reflect personal practice rather than established recommendations.

  • G-CSF, granulocyte colony-stimulating factor;JCV, John Cunningham virus; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorder; PML, progressive multifocal leukoencephalopathy; PRES, posterior reversible encephalopathy syndrome; RA, rheumatoid arthritis.