Recommendations for further research

The following are suggested as potential areas for further research:

GENERAL

1. The definition of early RA.
2. Clarification of the important factors for diagnosis and prognosis.
3. Inception cohort studies to investigate the combination of prognostic factors that will predict disease severity in individual patients and allow patients suitable for early aggressive therapy to be identified.
4. Evaluation of new imaging techniques to assess early joint damage.
5. Audit of referral time from symptom onset to rheumatology clinic appointment: resource implications of delay before specialist review.

PHARMACOLOGICAL MANAGEMENT

NSAIDs

1. Further evaluation of highly selective Cox2 agents:
   • will they reduce the incidence of ulcer complications in routine clinical practice?
   • will it be necessary for GI protective agents to be co-prescribed in patients at high risk of ulcer complications?
   • what effect will they have on NSAID- associated renal and cardiovascular events?
2. NSAIDs which block nitric oxide synthetase.

DMARDs

1. The optimum treatment strategy for achieving remission in early RA using existing/new DMARDs. This should include:
   • the most appropriate action if a patient fails to achieve an adequate response to methotrexate or sulphasalazine
   • long term, adequately powered studies of the combination of methotrexate and sulphasalazine in early disease
   • prospective study of other combination options
   • assessment of long-term safety issues.

CORTICOSTEROIDS

1. Long term, adequately powered studies to investigate whether continuous low-dose prednisolone and step-down prednisolone regimens will reduce joint damage/disability in the long term.
2. Assessment of cumulative toxicity.

TNF BLOCKADE AND NOVEL THERAPIES

1. The role of anti-TNF therapy in the treatment of patients with early RA:
   • as 'bridge therapy' to induce remission while waiting for DMARDs to take effect
   • in combination with DMARD therapy when there has been insufficient beneficial effect
   • as monotherapy in RA
   • the optimal dosage and method of administration of anti-TNF therapy and the issue of immunogenicity
   • efficacy of anti-TNF agents in preventing joint damage and maintaining function over the longer term
   • long term data on whether anti-TNF therapy will increase susceptibility to infection or tumours
   • pharmacoeconomic analyses of anti-TNF therapy including indirect costs associated with RA (e.g. disability and unemployment).
2. Evaluation of future possibilities for biological therapy in RA, such as:
   • IL-1 receptor blockade with recombinant human IL-1 receptor antagonist
   • blockade of IL-6 receptors
   • anti-inflammatory cytokines such as IL-10 and IL-4
   • targeting T-cells e.g. anti-CD4 antibodies.
3. Evaluation of matrix metalloproteinase inhibitors in early RA.

THE ROLE OF THE MULTIDISCIPLINARY TEAM

1. Evaluating early intervention by the multidisciplinary team versus medical care alone and the impact on functional ability.
2. Evaluation of rheumatology nurse specialist role.
3. Physiotherapy:
   • compliance with exercise and its relationship to longer term outcome
   • effect of exercise training programmes on muscle strength and function
   • inpatient versus outpatient physiotherapy in the management of early RA.
4. Occupational therapy
• efficacy of joint protection techniques.
5. Splinting
   • short and longer term evaluation of resting and working splints.
6. Podiatry
   • effect of foot orthoses on foot deformity and pain.
7. Dietetics
   • RCTs of dietary supplements such as antioxidants
   • urther research on the possible drug-sparing effect of fish oils.
8. Pharmacy
   • role of the pharmacist in patient education about drug therapy
   • the pharmacist's role in monitoring for drug interaction and side effects.

PATIENT INVOLVEMENT

1. The emotional impact of being diagnosed with RA and the value of psychological input.
2. Assessment of patient attitudes to early aggressive treatment.
3. Strategies to try to maintain patient employment: vocational assessment and retraining if necessary.
4. RCTs of educational interventions including patient led self-management courses in early RA (evaluating their impact on disability and emotional distress).
5. RCTs of psychological therapy such as cognitive behavioural therapy in early RA (evaluating their impact on disability and emotional distress).

OTHER ASPECTS

1. RCTs of complementary therapies in early RA evaluating benefit and harm.
2. Homeopathy in early RA.