Remarkable strides have been made in recent years in controlling clinical and radiological progression of RA. However, the usefulness of small molecules such as methotrexate remains and has not been overshadowed by the current interest in biological response modification. Our understanding of the molecular mechanisms responsible for the pathogenesis of RA has heralded a shift from empiricism to selective molecular targeting in immunomodulatory pharmacotherapeutics. While symptomatic control and reduction of the clinical signs of synovitis have been the foremost considerations in the past, modern pharmacotherapy has emphasized the need to slow down if not halt disease progression as well as prevention of the development of potential complications.

It is now recognized that significant radiological damage can occur in this disease much earlier than previously thought, certainly within the first 2 years of disease onset. Disease‐modifying therapy is therefore introduced early following confirmation of diagnosis, particularly in those with poor prognostic indicators such as severe disease activity, radiological damage or anticyclic citrullinated peptide positivity. The old ‘pyramidal’ treatment approach has been called into question and new advances have dramatically improved the disease outlook for the RA patient.

Non‐steroidal anti‐inflammatory drugs

Non‐steroidal anti‐inflammatory drugs are inhibitors of cyclo‐oxygenase, an enzyme that catalyses the conversion of arachidonic acid to prostanoids. The enzyme exists in two isoforms. Cyclooxygenase‐1 is constitutively expressed in many tissues, including platelets, blood vessels and the upper gastrointestinal mucosa where production of prostaglandin E₂ mediates a protective mucosal effect that includes mucus secretion and diminution of acid production. Expression of cyclooxygenase‐2 is induced at sites of inflammation, particularly on polymorphonuclear cells and macrophages. Thus, non‐selective inhibition of both isoforms by traditional NSAIDs may affect the desirable gastroprotective effects mediated by cyclooxygenase‐1, and reported hospitalization of RA patients as a result of upper gastrointestinal complications may exceed 1% of patients treated per year. Selective inhibition of cyclooxygenase‐2, on the other hand, has met with concerns over potential cardiovascular risks. Despite these concerns, NSAIDs continue to be used for symptomatic control in RA, but it must be emphasized that they have little effect in limiting joint damage or radiological progression.

Corticosteroids

The demonstration of the anti‐inflammatory efficacy of corticosteroids in RA resulted in the first Nobel prize awarded for a clinical observation, and 70 years hence, these potent anti‐inflammatory agents continue to have an important place in the management of RA. Furthermore, multiple routes of administration, including depot injections (methylprednisolone and triamcinolone acetonide) and local intra‐articular injections, offer a variety of therapeutic options. Given orally, the onset of action is quick and these agents are therefore useful in relieving symptoms while awaiting the onset of DMARD activity. Lower oral doses have been favoured (prednisolone up to 10 mg/day) owing to fear of suppressing the hypothalamus‐pituitary‐adrenal axis, and prevention of corticosteroid‐induced osteoporosis must be considered in patients receiving these medications long term.