Table 4.
Infection risk and immune function in patients being treated with cladribine tablets.
| Consensus recommendations | Strength of recommendation‡ | Level of consensus¶ |
|---|---|---|
| Q5a. How are patients with severe lymphopenia on cladribine tablets managed? (Level of evidence: moderate/low) | ||
| A patient with grade 3 or 4 lymphopenia on cladribine tablets may be at an increased risk of infection and should be actively monitored for signs and symptoms of infections. Clinicians should consider appropriate prophylactic treatment based on the individual patient’s risk. | 8 (8.2) | 93.8% (30/32) |
| A patient with grade 3 or 4 lymphopenia should be actively monitored for signs and symptoms particularly suggestive of herpes zoster. A patient should also be informed about the signs and symptoms of herpes zoster. If such signs and symptoms occur, anti-viral treatment should be initiated immediately. | 9 (8.6) | 96.9% (31/32) |
| Q5b. Do patients with severe lymphopenia on cladribine tablets need anti-viral prophylaxis against herpes zoster? Which anti-herpes therapy should be used prophylactically? (Level of evidence: moderate/low) | ||
| Initiation of anti-viral prophylaxis with a licenced anti-viral drug should be recommended in a patient with grade 4 lymphopenia.* | 8 (7.7) | 84.4% (27/32) |
| Initiation of anti-viral prophylaxis with a licenced anti-viral drug may be considered in a patient with grade 3 lymphopenia. Special consideration should be given to any patient at risk of herpes zoster infection such as elderly patients.*,** | 8 (7.4) | 75% (24/32) |
| Anti-viral prophylaxis should be maintained until severity of lymphopenia is reduced. | 8 (7.7) | 83.9% (26/31) |
| Vaccination with Shingrix may be considered for any patient at increased risk of herpes zoster infection (for example those with age ⩾50, previous herpetic exacerbations) | 8 (7.4) | 81.3% (26/32) |
| *Anti-viral prophylaxis could include: 200 mg acyclovir/day, 400 mg acyclovir/day, or 500 mg valaciclovir/day **Grade 3 lymphopenia was more common in year 2 of the CLARITY study, and duration of lymphopenia was longer. Zoster infection is more common in older patients. The history of the patient should be taken into consideration including the patient age, prior duration of lymphopenia and previous infection with varicella zoster virus. • Refer to Questions 6 and 7 for recommendations on vaccinations | ||
| Q6. What vaccinations are recommended as part of the de-risking strategy before patients are initiated with cladribine tablets? (Level of evidence: very low) | ||
| Clinicians should review a patient’s vaccination status before initiation with cladribine tablets and consult their local vaccination guidelines.* | 9 (8.4) | 93.8% (30/32) |
| Vaccination for varicella zoster virus is recommended in any antibody-negative patient prior to initiation of cladribine therapy. | 9 (8.7) | 96.9% (31/32) |
| *A review of a patient’s vaccination status includes the patient history and may also include a check of antibody titres. | ||
| Q7. How do you manage vaccinations after treatment with cladribine tablets; inactivated component vaccines versus live attenuated vaccines? (Level of evidence: low) | ||
| Cladribine tablets should not be initiated within 4–6 weeks after vaccination with live or attenuated live vaccines. | 9 (8.6) | 100% (31/31) |
| Any use of live attenuated vaccines should be avoided during treatment with cladribine tablets. Users should wait for the leukocytes/lymphocytes to return to normal wherever possible. | 9 (8.4) | 96.8% (30/31) |
| If an inactivated component vaccination is essential for a patient, clinicians should wait for the lymphocyte levels to return to within the normal range. | 8 (7.3) | 77.4% (24/31) |
| For certain multi-dose vaccinations,* clinicians may consider giving the first dose of the vaccine 4–6 weeks before treatment initiation with cladribine tablets. Subsequent vaccine dose(s) should be given at a later date, after initiation with cladribine tablets, once lymphocyte counts have recovered | 8 (8.1) | 93.5% (29/31) |
| *Relevant multi-dose vaccinations include those for HBV, HPV, VZV, measles, pneumococcus | ||
| Q8. How should latent or active infections be managed before initiation of cladribine tablets? [e.g. positive PPD/Quantiferon test for TB, HPV (cervical screening), HBV/HCV test, PML] (Level of evidence: low) | ||
| Cladribine tablets are contraindicated in a patient with HIV or an active chronic infection (e.g. HBV, HCV, VZV, Syphilis, TB, PML etc.), and a delay in initiation of cladribine tablets should be considered in a patient with an acute infection until the infection is fully controlled.* • In any case of infection (latent or active), a relevant specialist should be contacted (e.g. infectious disease, pulmonologist, hepatologist etc.). • The infection should be diagnosed, managed, and treated according to local guidelines. |
9 (8.5) | 96.8% (30/31) |
| Screening for PML is recommended in any patient previously treated with natalizumab, particularly those who are JCV antibody positive, and a baseline MRI (within 3 months) should be performed before initiation of cladribine tablets. Additional CSF analysis should be considered | 9 (7.7) | 83.3% (26/31) |
| *Clinicians should consider a patient’s prior treatment since those switching from a DMD associated with lymphopenia, may be at an increased risk from latent infections. | ||
‡
Median score on a 1–9 scale (mean score in brackets).
¶
Percentage of votes with 7–9 on a 9-point scale.
CSF, cerebrospinal fluid; DMD, disease modifying drug; HBV, hepatitis B virus; HCV, hepatitis C virus; HPV, human papillomavirus; JCV, John Cunningham virus; MRI, magnetic resonance imaging; PML, progressive multifocal leukoencephalopathy; PPD, purified protein derivative; TB, tuberculosis; VZV, varicella-zoster virus.