Introduction

Ankylosing spondylitis (AS) is the major subtype and a major outcome of an interrelated group of rheumatic diseases named ‘spondyloarthritides (SpA)’. The most important clinical features of this group are inflammatory back pain (IBP), asymmetric peripheral oligoarthritis, predominantly of the lower limbs, enthesitis and specific organ involvement, most frequently as anterior uveitis, and there are close associations with psoriasis and chronic inflammatory bowel disease (IBD) . For clinical purposes, two forms related to the predominant clinical manifestation – axial and peripheral SpA – and five subgroups – AS, SpA associated with psoriasis and IBD, reactive arthritis and undifferentiated SpA – are differentiated. Axial SpA including AS is the most frequent subtype of SpA, followed by psoriatic arthritis and undifferentiated SpA, while reactive arthritis and IBD-related SpA are less frequent.

The clinical symptoms of the SpA are characteristically similar and there is some evidence of genetic similarities, association and linkage but there is also heterogeneity. The strongest known contributing factor for AS, the major histocompatibility complex (MHC) class I molecule human leukocyte antigen (HLA)-B27, is known since 1973, while others such as endoplasmic reticulum aminopeptidase 1 (ERAP-1) and the interleukin (IL)-23R have only recently been identified . Of interest, IL23R gene polymorphisms have also been identified in psoriasis and IBD . However, the pathogenesis of the SpA is still largely obscure.

The SpA belongs to the most common rheumatic diseases with a prevalence of 0.5–1.9% – this is similar to rheumatoid arthritis (RA) . AS and PsA are the SpA subsets with the potentially most severe course of disease. The outcome is mainly influenced by the degree of disease activity over time and the loss of function and mobility, part of which is caused by inflammation, while the other part is due to radiographic damage of the spine and of peripheral joints . Male patients who are slightly more frequently affected than females have more radiographic progression . The degree of pain and disability of AS patients was found to be similar to RA . The quality of life of patients with AS is decreased in comparison to the normal population . The socio-economic burden due to AS has been studied in some detail pointing out that absence from work and work disability is threefold increased in AS patients – this leads to substantial direct and indirect costs. Worse physical function and high-disease activity have been identified as important determinants of costs. AS patients themselves also have substantial out-of-pocket costs .

Therapeutic options for patients suffering from the more severe forms of SpA have been limited during the last decades. Conventional disease-controlling anti-rheumatic therapy (DCART) has some efficacy in PsA and other SpA but only for peripheral and not for axial disease manifestations. However, data are limited. By contrast, symptom-modifying anti-rheumatic drugs (SMARDs) such as non-steroidal anti-inflammatory agents (NSAIDs) are currently considered the first choice of medical therapy. NSAIDs are widely used to ameliorate spinal pain in AS . Recent data have suggested that they may also have a DCART effect . Corticosteroids work mainly when given locally. Furthermore, there is a clear role for regular physiotherapy in AS to prevent loss of spinal mobility .

Taken together, before the introduction of anti-tumour necrosis factor (TNF) therapy about 12 years ago, there has been a clear need for more effective treatments in the SpA . Now there are four anti-TNF agents approved for the treatment of patients with active AS who have insufficiently responded to conventional therapies: infliximab, etanercept, adalimumab and golimumab. As far as it stands now, TNF blockers seem to have no influence on new bone formation in AS but they do inhibit radiographic damage in PsA. Other biologic agents have not been tested in AS, have had negative results or have only been tested in small open pilot studies .