Approach to immunomodulatory drug use

Australian Technical Advisory Group on Immunisation (ATAGI), 2022Buchbinder, 2008Buchbinder, 2015Hellgren, 2017Kavanaugh, 2014RACGP Red book taskforce, 2012Ramiro, 2014Singh, 2016van Assen, 2011

When someone is prescribed an immunomodulatory drug, they or their carer should be provided with information about the goals of treatment, potential adverse effects and how to minimise them, screening requirements before and during treatment, and the importance of follow-up.

The figures below outline what clinicians who care for people treated with immunomodulatory drugs should consider before therapy is started, and when reviewing people treated with immunomodulatory therapy. When drug-specific factors need to be considered, these are included in the tables in Additional considerations for specific immunomodulatory drugs. Also see Additional considerations for immunomodulatory drug use in children and adolescents.

Figure 1. Considerations before starting immunomodulatory therapy

Before immunomodulatory therapy is started, it is important that the person’s treating team:

For additional drug-specific considerations, see:

  • here for systemic corticosteroids
  • here for csDMARDs
  • here for b/tsDMARDs
Note:

b/tsDMARDs = biological or targeted-synthetic disease-modifying antirheumatic drugs; csDMARDs = conventional synthetic disease-modifying antirheumatic drugs

NB1: The results of these investigations may influence the choice of immunomodulatory drug and its dosing regimen, and provide a baseline measurement against which future results can be compared.

NB2: Data on the risk of malignancy with immunomodulatory therapy are conflicting and incomplete. While malignancy risk is known to be drug specific, the particular risk posed by individual immunomodulatory drugs has not been elucidated. For example, Australian data suggest an increased risk of melanoma in people with rheumatoid arthritis treated with methotrexate. However, it is not clear whether the increased risk relates to treatment with methotrexate or the disease process, and international studies have not replicated these findings. The choice of immunomodulatory drug in someone with a history of malignancy requires shared decision making between the person and their specialists, and should be informed by the benefit–harm profile of the treatment options in the individualStaples, 2019Wetzman, 2021.

NB3: The specialist will determine the appropriate monitoring regimen based on the adverse effect profile of the immunomodulatory drug(s) used and patient factors (eg disease activity, comorbidities). Monitoring is most frequent in the first 3 to 6 months of therapy, and after dose increases, because adverse effects are more likely. Once the person’s drug regimen and disease activity are stable, the frequency of monitoring can be reduced, but should not stop completely.

Figure 2. Considerations during immunomodulatory therapy

When reviewing someone after immunomodulatory therapy has started, it is important that the treating team:

  • asks about adherence to immunomodulatory therapy
  • assesses disease activity to determine whether the immunomodulatory therapy is effective [NB1]
  • assesses for adverse effects
  • monitors kidney, liver and bone marrow function, if required
  • ensures that vaccinations are up to date (see Assessing vaccination status in patients taking immunomodulatory drugs)
  • assesses people who present with fever, cough, systemic symptoms or unexplained illness for opportunistic infection, including tuberculosis and fungal infection (in particular Pneumocystis jirovecii)
  • continues to screen for and optimise the management of osteoporosis, residual pain and other common comorbidities (eg cardiovascular disease, diabetes, depression)
  • maintains vigilance for malignancy and ensures that malignancy screening appropriate for the person’s age and gender remains up to date [NB2]
  • refers people planning travel to an infectious diseases or travel medicine specialist for travel advice (eg vaccination, prevention and treatment of infection)
  • determines whether immunomodulatory therapy needs to be interrupted in people with an intercurrent infection; see Suggested approach for managing immunomodulatory therapy in people with an intercurrent infection.

Additional considerations also apply when immunomodulatory drugs are used for children or adolescents.

For additional drug-specific considerations, see:

  • here for systemic corticosteroids
  • here for csDMARDs
  • here for b/tsDMARDs
Note:

b/tsDMARDs = biological or targeted-synthetic disease-modifying antirheumatic drugs; csDMARDs = conventional synthetic disease-modifying antirheumatic drugs

NB1: Where appropriate, advice on specific disease targets is included in the clinical topics; the general practitioner should refer the person back to the specialist if these targets are not met.

NB2: This might include skin checks every 6 to 12 months (depending on skin type and sun exposure) to detect early skin cancer. Encourage people to monitor their skin for new or changing lesions. If malignancy is detected, immunomodulatory therapy may need to be interrupted—seek specialist advice.

Figure 3. Additional considerations for immunomodulatory drug use in children and adolescents

In addition to the considerations before therapy is started and during therapy, the treating team should note that children and adolescents:

  • have a higher likelihood of drug-free remission in some conditions (eg JIA, dermatomyositis)—dose reduction or a trial of discontinuation should be considered because it is more likely to succeed
  • often have less frequent screening for complications associated with immunomodulatory therapy because they tend to tolerate therapy better than adults and it can be difficult to obtain blood samples for monitoringBeukelman, 2011 2011.
Note:

JIA = Juvenile idiopathic arthritis