inflammatory process in inflammatory arthritis. Their mech-
anisms are generally poorly understood. They are used in
patients with progressive disease. Response (though unpre-
dictable) is usually maximal in four to ten weeks. Unlike
NSAIDs, DMARDs reduce inflammatory markers (historically,
it was this effect that led to them being referred to as ‘disease-
modifying’). It is difficult to prove that a drug influences the
natural history of a relapsing/remitting and unpredictably pro-
gressing disease, such as rheumatoid arthritis, but immuno-
suppressants retard the radiological progression of bony
erosions. DMARDs are toxic, necessitating careful patient mon-
itoring, and are best used by physicians experienced in rheuma-
tology. Rheumatologists use them earlier than in the past, with
close monitoring for toxicity, with the patient fully informed
about toxic, as well as desired, effects. This is especially impor-
tant since many of these drugs are licensed for quite different
indications to arthritis. In terms of efficacy, methotrexate,gold,
D-penicillamine,azathioprineandsulfasalazineare similar,
and are all more potent than hydroxychloroquine.Methotrexate
(Chapter 48) is better tolerated than the other DMARDs, and is
usually the first choice. Sulfasalazine(Chapter 34) is the second
choice. Alternative DMARDs, and some of their adverse effects,
are summarized in Table 26.1.
GOLD SALTS
Use
Goldwas originally introduced to treat tuberculosis. Although
ineffective, it was found to have antirheumatic properties and
has been used to treat patients with rheumatoid arthritis since
the 1920s. Sodium aurothiomalateis administered weekly by
deep intramuscular injection. About 75% of patients improve,
with a reduction in joint swelling, disappearance of rheuma-
toid nodules and a fall in C-reactive protein (CRP) levels. Urine
must be tested for protein and full blood count (with platelet
count and differential white cell count) performed before each
injection.Auranofinis an oral gold preparation with less tox-
icity, but less efficacy than aurothiomalate. Treatment should
be stopped if there is no response within six months.Mechanism of action
The precise mechanism of gold salts is unknown. Several
effects could contribute. Gold–albumin complexes are phago-
cytosed by macrophages and polymorphonuclear leukocytes
and concentrated in their lysosomes, where goldinhibits lyso-
somal enzymes that have been implicated in causing joint
damage. Goldbinds to sulphhydryl groups and inhibits
sulphhydryl–disulphide interchange in immunoglobulin and
complement, which could influence immune processes.Adverse effects
Adverse effects are common and severe:- Rashes are an indication to stop treatment, as they can
progress to exfoliation. - Photosensitive eruptions and urticaria are often preceded
by itching. - Glomerular injury can cause nephrotic syndrome.
Treatment must be withheld if more than a trace of
proteinuria is present, and should not be resumed until
the urine is protein free. - Blood dyscrasias (e.g. neutropenia) can develop rapidly.
170 ANTI-INFLAMMATORY DRUGS AND THE TREATMENT OF ARTHRITIS
Table 26.1:Disease-modifying antirheumatic drugs (DMARDs)
Drug Adverse effects Comments
Immunosuppressants: Blood dyscrasias, carcinogenesis, Methotrexate is usually the first-choice
azathioprine, methotrexate, opportunistic infection, alopecia, DMARD
ciclosporin nausea; methotrexate also causes
mucositis and cirrhosis; ciclosporin
causes nephrotoxicity, hypertension
and hyperkalaemiaSulfasalazine Blood dyscrasias, nausea, rashes, First introduced for arthritis, now used
colours urine/tears orange mainly in inflammatory bowel disease
(Chapter 34)Gold salts Rashes, nephrotic syndrome, Oral preparation (auranofin) more
blood dyscrasias, stomatitis, convenient, less toxic, but less effective than
diarrhoea intramuscular aurothiomalatePenicillamine Blood dyscrasias, proteinuria,
urticariaAntimalarials: chloroquine, Retinopathy, nausea, diarrhoea, See Chapter 47
hydroxychloroquine rashes, pigmentation of palate,
bleaching of hair