Therapy of ankylosing spondylitis. Part II: Biological therapies in the spondyloarthritides

Therapeutic options for patients with active and severe spondylarthritis (SpA) have been fairly limited in the past decades. There is now accumulating evidence that biological therapy with agents directed against tumour necrosis factor-alpha (TNF-alpha) is highly efficacious in the spondyloarthritides, especially in ankylosing spondylitis ( AS) and psoriatic arthritis (PsA). The TNF blocking agents currently available, infliximab (Remicade(R)), etanercept (Enbrel(R)), and adalimumab (Humira(R)), are approved for the treatment of rheumatoid arthritis ( RA) in Europe and the USA. In contrast to rheumatoid arthritis ( RA) disease-modifying anti-rheumatic drugs (DMARDs) have limited efficacy in SpA. No DMARDs are available for AS patients with active spinal disease. Thus, for AS patients whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs ( NSAIDs), therapy with TNF blockers may be considered as a first-line treatment. For infliximab, a dose of 3 - 5 mg/kg seems to be required, and intervals between 6 and 12 weeks are necessary to suppress disease activity continually. The standard dosage of etanercept is 2 x 25 mg subcutaneously (s.c.) per week. There are very few studies with adalimumab ( standard dose in RA 20 - 40 mg s.c. every 1 - 2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. There is some evidence that both agents also work in other SpA, especially in PsA. Withdrawal of long-term therapy in AS patients led to relapses of disease after several months. Less radiographic progression after 2 years of continuous treatment with infliximab compared to conventional therapy has been suggested in a small study. Serious adverse events on anti-TNF therapy have remained rare. However, severe infections, including tuberculosis, have been reported. These can be largely prevented by appropriate screening. The benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.