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The British Society of Rheumatology has produced a set of NICE accredited guidelines for the use of biologic therapies in patients with inflammatory arthritis.
It addresses safety recommendations for all biologic therapies approved by the National Institute for Health and Care Excellence (NICE) up to June 2016, for use in all inflammatory arthritides [RA, PsA and axial SpA (SpA) including AS].
These evidence based guidelines addressed biologic safety by asking about screening measures, monitoring, and comorbidity issues. Below are a sampling of several key recommendations - please consult the Rheumatology link provided for acomplete listing of guidelines.
- The decision to initiate a biologic should shared with the patient, and initiated by an expert
- Patients should be provided with education about their treatments
- Patients should be assessed for co-morbidities
- Patients should have access to their specialist centre for advice within one working day
- For all biologics: Baseline laboratory assessment - CBC, CMP, LFTs, TST or IGRA, serology for HCV, HBV, CXR
- RTX: should have baseline IgA, IgG and IgM) prior to initiation
- TCZ: a baseline lipid profile
Comorbidity Screening Pre-treatment
- Biologics should not be initiated in the presence of serious active infections (IV antibiotics or hospitalization; not tuberculosis)
- Use biologics with caution in patients at high infection risk
- Consider ETN or ABA as a first line biologic therapy in patients at high risk of infection
- Mycobacterium tuberculosis: screening for TB before starting a biologic
- Screening for TB - check for previous TB exposure, clinical examination, CXR and either a TST or IGRA
- Patients with an abnormal CXR, previous history of TB or TB treatment should be referred to a TB specialist prior to commencing a biologic
- Immunocompromised patients screened for latent TB with an IGRA alone or together with a TST and found to have a positive result in either test should be considered for treatment prior to starting biologic therapy
- Latent and reactivated TB - Patients should be treated with prophylactic anti-TB treatment prior to commencing a biologic; therapy may be commenced after completing at least 1 month of anti-TB treatment and patients should be monitored every 3 months
- Patients who have had previous inadequate treatment for active TB should be investigated for active TB.
- TB reactivation risk is higher with anti-TNF mAb drugs (notably ADA and IFX) than for ETN, consider ETN in preference for those who require anti-TNF therapy and are at high risk of TB reactivation
- Active TB: Patients with evidence of active TB should be treated before starting a biologic; therapy may be commenced after completing at least 3 months of anti-TB treatment, and there is evidence that the patient is improving with evidence of culture negativity
HBV and HCV
- Patients should be screened for HBV and HCV infection
- HBV positive patients: a risk–benefit assessment should be undertaken, working closely with a hepatologist.
- HCV infection: use biologic with caution in such patients
- Biologic therapies should not be commenced in patients with clinical signs of, or under investigation for, malignancy (basal cell carcinoma excluded)
- Patients should be advised that there is no conclusive evidence for an increased risk of solid tumours or lymphoproliferative disease linked with biologic therapy, but that on-going vigilance is required
- There is conflicting evidence regarding the risk of skin cancers with anti-TNF therapy; patients should be advised of the need for preventative skin care, skin surveillance and prompt reporting of new persistent skin lesions
- Anti-TNF therapy is relatively contraindicated in patients who have had prior treatment with >150 psoralen and ultraviolet A (PUVA) and/or >350 ultraviolet B (UVB) phototherapy.
- Caution should be exercised in the use of biologics in patients with previous malignancy. The timing of commencement of biologic therapy post-malignancy is not fixed and will depend on type and stage of malignancy, risk of metastasis and patient views. RTX may be considered as a first-line biologic option in RA patients with previous malignancy
- The effect of biologics on pre-malignant conditions remains unclear. Caution should be exercised in the use of biologics in such patients. RTX may be considered as a first-line biologic option is these patients
- Although recent data are reassuring, biologics should be used with caution in patients with class III or IV cardiac failure, working closely with a cardiologist
- Biologic therapy may be used in patients with previous myocardial infarction or cardiovascular events
- Pre-existing interstitial lung disease (ILD) is not a specific contraindication to biologic therapy; however, caution is advised in patients with poor respiratory reserve (in whom a significant drop in lung function would be potentially life threatening); in this situation it is advised to work closely with a respiratory physician with a specialist interest in ILD
- RTX or ABA may be considered a first-line biologic in patients with ILD
- ADA and IFX can be considered for the treatment of uveitis, in preference to ETN, which appears to be associated with lower rates of treatment success and has been associated with the development of uveitis. The relative risks of the available agents should be taken into account when selecting which treatment to use
- Anti-TNF therapy should not be given when there is a personal history of multiple sclerosis or other demyelinating diseases. Consider using a non-anti-TNF biologic in this situation
- Exercise caution with TCZ in patients with diverticular disease, particularly when using concurrent NSAIDs and/or steroids
- Patients >50 years should undergo vaccination against herpes zoster assuming there are no contraindications (e.g. treatment within the past 3 months with >40 mg prednisolone per day for >1 week, >20 mg prednisolone per day for >14 days, MTX >25 mg/week, AZA >3.0 mg/kg/day). This should be administered preferably >14 days before starting biologic therapy
- Patients who do not have a positive history of varicella zoster (chickenpox) infection should have a varicella zoster virus antibody test. If this is negative, and there are no contraindications (as listed in 3.31), varicella zoster vaccination should be offered prior to biologic commencement
Monitoring on Biologic treatment
- All patients should be reviewed for drug safety in a specialist department at least every 6 months. High risk patients (e.g. those at high risk of TB) should be reviewed every 3 months
- Patients prescribed a biologic (other than TCZ) without concomitant csDMARD (or with csDMARDs that do not require blood test monitoring), should have monitoring blood tests (CBC, creatinine/calculated GFR, ALT and/or AST and albumin every 3–6 months
- Patients receiving csDMARD may require more regular laboratory monitoring
- Patients receiving RTX should have serum immunoglobulins (especially IgG and IgM) checked prior to each cycle of RTX. Clinicians and patients should be aware that the risk of infection increases as serum IgG levels fall below normal
- Patients receiving TCZ, with or without MTX, should have laboratory monitoring every 4 weeks for neutrophils and ALT/AST (grade 2B). Blood tests should ideally be in the week before i.v. TCZ, and in the 3 days before every fourth s.c. injection. Any decision to halt treatment should be made in accordance with the guidance in the TCZ SPC
- Patients receiving TCZ should have their serum lipids checked at 3 months, and be treated appropriately if abnormal; they may be checked again thereafter at physician’s discretion
- For most biologics (exceptions: RTX and TCZ), consideration should be given to planning surgery when at least one dosing interval has elapsed for that specific drug; for higher risk procedures consider stopping 3–5 half-lives before surgery (if this is longer than one dosing interval)
- Biologics may be recommenced after surgery when is good wound healing (typically around 14 days), all sutures and staples are out, and there is no evidence of infection
- For patients receiving RTX, treatment should ideally be stopped 3–6 months prior to elective surgery
- For patients receiving TCZ, i.v. TCZ should be stopped at least 4 weeks before surgery; s.c. TCZ should be stopped at least 2 weeks before surgery (grade 1C, SOA 96%).