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Modern Management Of Rheumatoid Arthritis (RA)
Dr. Terence Gibson (MD, FRCP)
Beyond doubt, the containment but not the cure of RA is within our grasp.
It has become a tenet of treatment that once the diagnosis has been established
and if symptoms warrant, a Disease Modifying Anti Rheumatoid Drug (DMARD)
should be deployed without hesitation. The initial choice of agent is
methotrexate. Given weekly with folic acid on a separate day, it is better
tolerated than any other DMARD (Table1) although it is no more effective
at reducing pain and swelling than the other agents.1
All DMARDs may retard but do not halt radiographic progressions2.
There is uncertainty of whether combinations of DMARDs containing methotrexate
are any more effective than methotrexate itself 3 although
it has become common practice to commence with either two or three drugs
simultaneously or to add successive preparations depending on the response
to one, two or three of them. The most popular combination is of methotrexate,
sulfasalazine and hydroxychloroquine. Similar controversy surrounds the
use of corticosteroids as part of a combination treatment.There is convincing
evidence that low dose prednisolone given concomitanly with a DMARD results
in a slowing of radiographic damage.4 Whether this translates
into long-term preservation of function or an acceptable level of cumulative
side effects is what divides opinion. Patients will often influence a
decision about steroid usage since knowledge of its toxicity is widespread.
There is no argument about the usefulness of intra-articular or short-term
courses of intramuscular injections of long acting steroid preparations,
especially in patients awaiting a response to recently initiated DMARD
therapy.5
The advent of anti-TNF alpha treatment has not entirely transformed the
outcome of RA. While representing an important advance and having a demonstrably
stronger impact than DMARDs on radiological progression, only 60% of patients
derive long-term clinical benefits.6 Primary failure and relapse
are common with all three preparations currently in use namely infliximab,
etanercept and adalimumab. The first has the disadvantages of requiring
intravenous infusion facilities and while the latter two are given by
self-administered subcutaneous injection, all are expensive. The hazards
of opportunistic tuberculosis infection are accentuated in countries where
tuberculosis is endemic, another reason beyond cost for their careful
and restricted use in India.
The symptom that preoccupies patients is pain.7 In addition
to what can be achieved with DMARDs there is a need for analgesia. The
concomitant use of a simple analgesic and a Non Steroidal Anti-inflammatory
(NSAID) has an additive effect.8 The conventional NSAIDs are
likely to be entirely replaced by Cox2 inhibitors such as rofecoxib and
its many successors. However, while reducing the risk of peptic ulcer
and gastrointestinal blood loss, these drugs do not eliminate the risk
of renal impairment especially in the older population.
Despite the best available treatment, life expectancy is still reduced
in RA, radiological progression continues and the need for orthopedic
intervention is likely to continue indefinitely.9 About half
of all patients with RA for 20 years currently require a large joint replacement.
The surgical possibilities are now many with successful prostheses for
hip, knee, shoulder, elbow and fingers. Newer techniques involve femoral
head resurfacing and multiple revisions. Cartilage implantation remains
experimental but stem cell research holds out promise.
The onset of RA in both men and women can have devastating psychological
impact but especially on young women of child bearing age. Early contact
with an experienced nurse or therapist specifically to provide counseling
can mitigate the reactive depression and despair which are so common.
At this stage, expert advice on the balance of rest and exercise can help
preserve muscle strength is recommended. In later disease, especially
after orthopedic surgery or co-morbid illness, rehabilitation may entail
physiotherapy to help restore mobility and occupational therapy which
may entail the provision of walking sticks or frames and home appliances
to assist daily activities. Structural alterations to the house may include
the creation of ramps, rails, lifts and accessible bathing and toilet
facilities.
REFERENCES
1. Pincus T, Marcum S, Callahan L. Long-term drug therapy for rheumatoid
arthritis in seven Rheumatology private practices: eleven second line
drugs and prednisone. J. Rheumatol. 1992; 19: 1885-94.
2. Gradual N, Jarik A, de carvalho A, Gradual H. Radiographic progression
in rheumatoid arthritis. A long-term prospective study of 109 patients.
Arthritis Rheum. 1998; 41:1470-80
3. Willkens R, Urowitz M, Stablein M, et al. Comparison of azathioprine,
methotrexate and the combination of both in the treatment of rheumatoid
arthritis. Arthritis Rheum. 1992; 35: 1779-1806.
4. Kirwan J. The effect of glucocorticoids on joint destruction in rheumatoid
arthritis. N.Eng. J Med. 1995; 333: 142-6
5. Corkill M, Kirkham B, Chikanza I, Gibson T, Panayi G. Intramuscular
depot methyl prednisolone induction of chrysotherapy inrheumatoid arthritis:
24 week randomized controlled trail. Br. J. Rheumatol.1990; 29:274-9
6. Genovese M, Bathon J, Martin R. et al. Etanercept versus methotrexate
in patients with early rheumatoid arthritis: two year radiographic and
clinical outcomes. Arthritis Rheum 2002; 46: 1443-50
7. Gibson T, Clark B. simple analgesic use in rheumatoid arthritis. Ann.
Rheum. Dis 1985; 44:27-9
8. Emery P, Gibson T, A double blind study of the simple analgesic nefopam
in rheumatoid arthritis. Br. J Rheumatol. 1980;25:72-6
9. Gordon P, West J, Jones H, Gibson T. A 10 years prospective follows
up patients with rheumatoid arthritis 1986-96. J. Rheumatol. 2001; 28:
2409-15.
10. Gibson T, Grahamme R. Rehabilitation of the elderly arthritic patient,Clinics.
Rheum Dis. 1981; 7: 485-95
TABLE 1
Available Disease Modifying Drugs
1. Methotrexate - inhibits purine
synthesis
2. Leflunomide -
inhibits pyrimidine synthesis
3. Sulfasalazine - poorly absorbed,
effect on Peyers patches
4. Azathioprine - inhibits
purine synthesis
5. Cyclosporine A - t-cell suppressor
6. Sodium
aurothiomalate - restores
t-cell function
7. D-penicillamine - heavy metal chelation
8. Hydroxychloroquine - action uncertain, less effective than
drugs1-7
TABLE 2
TNF alpha inhibitors
1. Infliximab - Chimeric monoclonal
2. Etanercept - recombinant TNF receptor fusion protein
3.Adalimumab - Human monoclonal anti TNF alpha antibody.
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