Global Trials Affirms the Safety Profile of Adalimumab in RA and Other Inflammatory Diseases

 Burmester GR, Panaccione R, Gordon KB et al, Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s diseaseAnn Rheum Dis. (2013) 72: 517–524

An analysis of adverse events in 17 global clinical trials of adalimumab (Humira) confirms the drug’s safety profile over nearly a dozen years of use. Serious infections were the most common side effect. The analysis among 23,458 trial participants over 12 years of exposure is the largest safety database published for an anti-TNF drug.

Safety assessments encompassed serious infectious events, active tuberculosis (TB), and malignancies occurring up to 70 days after the last study dose of adalimumab. The average age of the patients was 48 and most had rheumatoid arthritis (n=14,109).

While some differences in rates of serious infections were seen among indications for which adalimumab is approved – RA, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), psoriasis (Ps) and Crohn’s disease (CD) -- the overall rate was consistent with previous safety analyses. The greatest incidence for serious infections per 100 patient-years (100/PYs) was seen in RA and in CD (4.6 100/PYs and 6.7 100/PYs respectively), with the most common being cellulitis and pneumonia.

The risk of serious infections was stable across all indications and 70% of patients continued with therapy. Death rates were lower than, or equivalent to, those expected in the general population, the researchers said. The incidence rate for active TB was 0.2/100 PYs across all indications, a drop from 1.5/100 PYs since tuberculin test screening and prophylaxis were implemented in 1998-1999.

For malignancies, the rates were similar to those previously reported, at 0.1/100 PYs for lymphoma, 0.2/100 PYs for nonmelanoma skin cancers, and 0.7/100 PYs for all other cancers. Other adverse events included demyelinating disorders, lupus-like syndrome, congestive heart failure, and new onset or worsening of psoriasis.

The 17 adalimumab trials were conducted in Europe, North America, South America, Asia, Australia, New Zealand and South Africa.