Recommendations for research
The guideline committee has made the following high-priority recommendations for research.
What is the clinical and cost effectiveness of analgesic drugs other than non-steroidal anti-inflammatory drugs (NSAIDs) in adults with rheumatoid arthritis (RA) whose pain or stiffness control is not adequate?
Analgesics (including NSAIDs, paracetamol, opioids and compound analgesics) are sometimes used with disease-modifying treatments to relieve pain and stiffness when symptom control is inadequate. Current practice regarding the choice of analgesic in RA is variable. The evidence is limited for many of the analgesic drugs other than NSAIDs, and their relative effectiveness is unknown. Further research in this area may inform future guidance on the use of analgesic drugs other than NSAIDs for controlling symptoms.
What is the clinical and cost effectiveness of short-term bridging treatment with glucocorticoids for adults with RA starting a new disease-modifying anti-rheumatic drug (DMARD), including the most effective dosing strategy and mode of administration?
All DMARDs have a slow onset of action. In some cases, response may not be seen for 2 to 3 months. In contrast, glucocorticoids have an immediate effect on joint pain and swelling. In clinical practice, several different regimens are prescribed to 'bridge' the time between the initial prescription of DMARDs and the clinical response. However, good quality evidence from randomised controlled trials (RCTs) demonstrating the effectiveness of glucocorticoids as bridging treatment is limited and inconclusive. Further research is needed to inform recommendations for practice regarding whether bridging treatment with steroids should be used until the new DMARD begins to take effect.
The optimal dosing strategy and mode of administration for bridging glucocorticoids also needs to be established. Although the anti-inflammatory response is dose dependent, side effects of glucocorticoids vary according to both the dose and the duration of treatment.
What is the clinical and cost effectiveness of using ultrasound to monitor disease in adults with RA when clinical examination is inconclusive or inconsistent with other signs of disease activity?
RA is a chronic inflammatory condition that needs regular review to enable adjustments in management to achieve a target of remission or low disease activity.
Although ultrasound is able to show subclinical inflammation or erosions in some people in clinical remission, evidence from RCTs does not support using ultrasound for routine monitoring. However, ultrasound may be useful for assessing disease activity in some people with RA; specifically, when clinical examination is inconclusive or is inconsistent with other signs of disease activity (for example, pain or markers of inflammation). There is no reliable evidence on the added value of ultrasound as part of a monitoring strategy in these subgroups.
In addition, when there is inconsistency between clinical examination and disease activity, it may be unclear if the person has subclinical inflammatory synovitis or more of a widespread pain syndrome, which is not inflammatory. These need very different treatments, so it is important to define them accurately.
What is the clinical and cost effectiveness of using ultrasound in addition to clinical assessment when there is uncertainty about the diagnosis in adults with suspected RA?
Early diagnosis of RA is essential to reduce the impact of the disease on multiple systems in the body. The course of RA and the initial presentation can be highly variable; most people with RA have definite synovitis on clinical assessment, but sometimes this is not obvious, leading to uncertainty about the diagnosis. Ultrasound is a non-invasive and relatively inexpensive imaging modality that can detect subclinical synovitis and early erosive disease. It might help determine an early diagnosis of RA when the diagnosis would otherwise be uncertain. Early diagnosis enables earlier treatment, providing an opportunity to improve the longer term outcomes for people with RA. The use of ultrasound may also allow healthcare professionals to be more confident about ruling out a diagnosis of RA.
What is the clinical and cost effectiveness of managing RA with a poor prognosis (identified as presence of anti-cyclic citrullinated peptide [CCP] antibodies or evidence of erosions on X-ray at diagnosis) with a different strategy from that used for standard management of RA?
Current recommendations suggest all people with RA should be offered the same management; however clinical experience suggests that the condition responds less well in some people and some suffer progressive radiographic damage and impaired function despite standard management. Several factors have been identified in the literature that, if present and identified early in the course of the disease, may predict a poor prognosis (greater radiographic progression). These include anti-CCP antibody positivity and the presence of radiographic erosions at baseline. At present it is unclear whether people with poor prognostic markers should have different management early in the disease, and whether this would improve radiographic and functional (HAQ) outcomes in this group.
What is the clinical and cost effectiveness of subcutaneous methotrexate compared with oral methotrexate for adults with early onset RA starting a new DMARD?
Methotrexate is an important drug in the treatment of RA. Subcutaneous administration is an alternative option for people who have side effects with oral treatment. Evidence on the effectiveness of subcutaneous methotrexate is lacking, but its effects may be superior, due to increased bioavailability, and fewer side effects than with oral drugs. Research on subcutaneous methotrexate will inform future guideline recommendations.