24th February 2025

Management of RA

The key treatment aim in RA is to intensively pursue remission to prevent deformity and disability. Tools such as the Disease Activity Score 28 Joints (DAS-28) are used to assess the treatment response over time in a patient-centred way.

The initial step of the treatment ladder usually consists of a DMARD and a corticosteroid (whilst the DMARD takes effect). Typically, methotrexate is used first-line. If a clinical response is not seen within 3-6 months, or if it is not tolerated, then it will be substituted for one of either hydroxychloroquine, sulfasalazine or leflunomide. The following table details the monitoring required and the potential side effects of each of these agents:

Table 2 DMARDs used in RA with their monitoring requirements and side effects (not an exhaustive list)

The next step, if remission is not induced at the maximum tolerated doses of two different DMARDs combined (one of which is usually methotrexate), is the addition of a biologic agent to the DMARD (ideally methotrexate). The first-line anti-TNF-ɑ drugs are adalimumab, etanercept and infliximab. If remission is still not achieved, then an alternative biologic is tried, such as anti-CD-20 drug (rituximab) or anti-IL-6 drug (tocilizumab).

Again, these drugs require careful monitoring and, because they are powerful immunosuppressants, require certain investigations prior to their initiation. This normally includes excluding tuberculosis (risk stratifying, chest X-ray and IgRA, interferon-gamma release assay), hepatitis, HIV and ANA positivity (can cause an SLE-like syndrome when started on anti-TNF-ɑ drugs). Additionally, demyelinating disorders, congestive cardiac failure, interstitial lung disease and uveitis require caution when considering initiation, as all of these conditions can be exacerbated by anti-TNF-ɑ drugs. Interestingly, anti-TNF-ɑ therapies have also been associated with the recurrence of previous malignancies and de novo skin cancers (but not solid tumours). The decision to initiate should be made on an individual risk/benefit basis.

Once remission has been induced, the corticosteroid is gradually weaned. Patients on these medications should be carefully counselled about seeking medical help when feeling unwell as they are prone to infections with opportunistic or rare organisms such as herpes zoster (for which immunoglobulin should be given) or fungi. In the context of suspected sepsis, they require aggressive broad-spectrum antimicrobial therapy and require their DMARDs and biologics to be held and their corticosteroids (if they are on them) to be up-titrated during their illness, as they are at risk of adrenal insufficiency in times of physiological stress.

Effective analgesia usually includes paracetamol and ibuprofen (often with gastroprotection).