Rheumatoid arthritis is associated with an increased risk of serious infection, and GPs have an important role to play in managing these risks. Read more about how primary care physicians can do so through encouraging vaccinations, timely treatment and prompt referrals to specialists when necessary.


Rheumatoid arthritis (RA) is the commonest autoimmune inflammatory arthritis, and its treatment has advanced significantly over the last two decades. While prednisolone and conventional synthetic disease-modifying anti-rheumatic drugs (cs-DMARDs) remain an essential part of RA management, biologics and small molecules have revolutionised the treatment paradigm.


Methotrexate, sulfasalazine, hydroxychloroquine and leflunomide are the commonest medications prescribed for RA patients.

An increasing number of patients are on biologics such as:

  • Anti-tumour necrosis factors (anti-TNFs) (infliximab, adalimumab and golimumab)
  • Anti-interleukin-6 (anti-IL6) (tocilizumab)
  • B-cell depletion (rituximab)

A new class of drugs called Janus kinase inhibitors (JAK inhibitors), like tofacitinib and baricitinib, are also playing a more important role in recent years.

The availability of biosimilars for adalimumab and rituximab have made biologics more accessible due to their lower costs.


Rheumatoid arthritis is known to be associated with increased risk of serious infection. Observational studies and cohort studies demonstrated more than a two-fold higher risk of serious infection among RA patients.

The contributing factors include:

  • The pathobiology of the underlying disease
  • Comorbidities associated with RA
  • Medications such as prednisolone, cs-DMARDs and biologics

To reduce the risk of infection risks, we generally advise our patients to:

  • Practise social distancing from people who are unwell with infection
  • Practise good hand hygiene
  • Avoid raw or half-cooked food
  • Stay up-to-date on their vaccinations
  • Stop smoking
  • Take good care of their comorbidities (e.g., diabetes mellitus)


Encouraging vaccinations

In primary care, GPs can encourage RA patients to get vaccinated against influenza and pneumococcal pneumonia.

In the current COVID-19 pandemic, many patients with RA patients are deemed moderately-to-severely immunocompromised. They are encouraged to receive their COVID-19 vaccine enhanced primary series and subsequent booster dose.

Other vaccines like Shingrix can be considered.

In general, live virus or live attenuated vaccines are contraindicated in patients receiving DMARDs. More details can be obtained from the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) guidelines1-2.

Timely treatment

The infections of RA patients should be treated in a timely manner to avoid clinical deterioration. If a bacterial or serious viral infection is suspected, in addition to appropriate antibiotics or antiviral drugs, DMARDs can be suspended until antimicrobial treatment is completed and the infection is resolved.

Communication and collaboration with the rheumatologist

If the patient being treated has multiple infections, GPs can alert the rheumatologist who will consider modifying the treatment regime. RA treatment can carefully balance the risk of infections and the benefits of getting the disease controlled. In the situation of frequent infections, rheumatologists may favour cs-DMARDs over biologics, or may favour DMARDs with shorter half-lives.

Careful diagnosis and prompt referral

When assessing an RA patient with joint flare, it is important to look out for features of septic arthritis.

During the assessment of any infection in RA patients, it is important to recognise that the classic symptoms of infections might not be present, especially when the patients are taking prednisolone.

Patients with prednisolone may not exhibit fever or other classic symptoms of inflammation. One example is tocilizumab, a biologic that is associated with intestinal perforation. The presence of prednisolone may delay the diagnosis of intestinal perforation and related sepsis.

Due to the complex nature of the disease and medications like biologics and JAK inhibitors that are immunosuppressive, tuberculous infection, opportunistic infections, and atypical infections could be considered and referred promptly.


Dr Ng Chin Teck is a Senior Consultant in the Department of Rheumatology and Immunology at Singapore General Hospital (SGH). He has a special interest in rheumatoid arthritis and early arthritis.

GPs who would like more information about this topic, please contact Dr Ng at ng.chin.teck@singhealth.com.sg.


  1. EULAR: https://www.eular.org/recommendations_management.cfm
  2. ACR: https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Rheumatoid-Arthritis