Adalimumab (Humira) Appears Safe, Effective in Treatment of DMARD Refractory RA

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Adalimumab Appears Safe, Effective in the Treatment of Disease Modifying

Antirheumatic Drug Refractory Rheumatoid Arthritis

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A DGReview of : " Efficacy and safety of the fully human anti-tumour

necrosis factor alpha monoclonal antibody adalimumab (D2E7) in DMARD

refractory patients with rheumatoid arthritis: a 12 week, phase II study "

ls of the Rheumatic Diseases 2003 Dec;62:12:1168-1177.

Rapid and significant improvements are seen with self-administered

adalimumab treatment in patients with longstanding rheumatoid arthritis

(RA) who are refractory to disease modifying antirheumatic drugs

(DMARDs), according to results from a phase II, multicentre study.

Early diagnosis and aggressive treatment are necessary for successful

long-term outcome in patients with RA. Traditional treatments range from

nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids that

provided temporary pain relief to DMARDs, which have been shown to slow

the progression of joint destruction.

New therapies targeting tumour necrosis factor alpha (TNF-alpha) have

been developed to treat patients who are refractory to traditional

DMARDs. Adalimumab (D2E7) is the first fully human anti-TNFa monoclonal

antibody to enter clinical trials for the treatment of RA. Early studies

have suggested that adalimumab may be effective in patients with DMARD

refractory active RA.

Leo BA van de Putte, MD, at the University Medical Centre Nijmegen, the

Netherlands, and colleagues therefore initiated a phase II clinical

trial to evaluate the potential use of adalimumab (D2E7) in patients

with longstanding, active RA who were refractory to previous DMARD therapy.

The double-blind study included 284 patients, mostly women, who were

randomised to receive weekly self-administered subcutaneous injections

of adalimumab (20 mg, 40 mg, or 80 mg) or placebo for 12 weeks. All

patients had failed at least one DMARD therapy and more than half had

taken 4 to 8 different DMARDs. Notably, patients did not take DMARDs

during the course of the study.

About half of the patients showed an ACR20 response after 12 weeks of

adalimumab, while only 10% of patients given placebo responded.

Moreover, 71% of adalimumab responders had an ACR20 response after just

2 weeks of treatment.

In addition, significantly more patients given adalimumab achieved an

ACR50 (19%-27%) and ACR70 (8%-11%) response by week 12 as compared to

placebo (1% and no patients, respectively).

Adalimumab treatment was also associated with rapid and significant

improvement in the signs and symptoms of RA. An immediate decrease in

tender joint count was seen after the first adalimumab injection.

Furthermore, a significant decline was also seen in the mean number of

swollen joints and in HAQ disability scores.

Hyperlipidaemia (triglycerides >2.26 mmol/L) and injection site

reactions, including erythema and/or itching, haemorrhage, swelling, or

pain, occurred more frequently (>10%) in patients injected with

adalimumab than in those given placebo. A similar incidence of serious

adverse events occurred in treated and control patients.

The investigators conclude that " adalimumab treatment significantly

altered the course of disease in patients who had considerable disease

activity of long duration and who had not adequately responded to

traditional DMARDs. " They further add that " adalimumab treatment was

safe and convenient, allowing patients to self administer the sc

injections at home. "