Treatment goals in RA include:
- Control of synovitis and pain
- Maintenance of joint function
- Prevention of deformities
A multidisciplinary approach is essential, involving pharmacotherapy, physiotherapy and occasionally surgery. Pharmacotherapy is the cornerstone of treatment in RA and has significantly reduced the number of patients requiring surgery in the past decade. The main changes in treatment have been the use of disease-modifying anti-rheumaric drugs (DMARDs) at an earlier stage in the disease, and the introduction of new “biologic” drugs that are antibodies which directly interfere with the disease process.
The most commonly used DMARD is methotrexate (Jurgens 2011), and this is usually considered the “anchor drug” for combination drug regimes. Other DMARDs include:
Gold, penicillamine and azathioprine are now less commonly used as they are less effective and/or more toxic. Methotrexate is now started early in treatment. Combination with leflunomide or sulphasalazine + hydroxychloroquine may improve disease control, especially in patients with high disease activity (Jurgens 2011).
Currently five antagonists of TNF-α are available (Ferraccioli 2011, Thalayasingam 2011):
There are no RCTs comparing these agents directly. Adalimumab appears to have the highest disease suppression rate, while etanercept appears to be best tolerated. Combination therapy using etanercept and methotrexate has a higher remission rate and patients on this regime are more likely to continue therapy. Rituximab inhibits B cells and abatacept T cells.
Effects on disease progress
Early treatment with DMARDs appears to reduce the rate of joint damage. A trial comparing sulphasalazine with methotrexate-sulphasalazine-hydroxychloroquine (Rantalaiho 2010) reported joint erosions in 13% of patients in combined therapy at 11 years, compared with 28% of the monotherapy group. There was no placebo control, but historical controls had an equivalent level of joint damage after 3 years. Bosello (2011) reported a study of aggressive treatment of early RA, in which patients started methotrexate at diagnosis and might have steroids or biologics added. After 12 months, patients who were treated within 12 weeks of disease onset were least likely to have developed new erosions.
There has been a reduction in some presentations for surgery over the last few decades. Rates of knee, hip and ankle surgery in California peaked in the 1990s in patients under 60y and have fallen by 20-40% since; however, rates in patients over 60y increased in line with those in a degenerative population (Louie 2010). Similar results have been reported from Sweden (Weiss 2006). However, rates of surgery were stable in Japan from 1998-2008, and some procedures, including forefoot arthroplasty, increased slightly. Anecdotally, there is a tendency for patients to present now with better-preserved joints, raising the possibility of successful joint-preserving surgery; however, there is not yet much data on the long-term durability of such procedures (see below).
DMARDs, infection and perioperative medical management
Biologic agents increase the risk of infection, occasionally catastrophically. Galloway (2011) found an increase in serious infection from 32/100,000 patient years to 42/100,000. Da Cunha (2012) reported a systematic review of the perioperative infection risk in orthopaedic surgery. The best evidence is a large retrospective study (den Broeder 2007) which found no significant difference in infection rates between patients who used anti-TNF drugs and those who had never used them (although the 95% confidence intervals of the odds ratio were 0.98 to 3.44); however, there was an increase in wound healing problems in the patients who had used anti-TNF drugs (OR 11.2, 95% CI 1.4-90). No difference in either event was found in patients who continued drugs through the perioperative period versus those who stopped, but the numbers were small. Kubota (2012) found no difference in either infection or wound problems in 550 patients, including about 100 foot and ankle patients, but all patients stopped biologics prior to surgery. There is also an increase in TB reactivation and other opportunistic infections. The current recommendation is to stop biologics 5 half-lives prior to surgery (15 days for etanercept, although Veetil (2012) felt this led to excess disease flares and recommended withholding for one dose cycle (4-7 days for etanercept).
On the other hand, Grennan (2001) reported an RCT showing that continuing methotrexate in the perioperative period reduced the rate of infection and other wound problems compared with stopping, and prevented rheumatoid flare-ups. Veetil (2012) confirmed that observational studies support continuing methotrexate at the time of surgery.
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