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Therapeutic options for severe ankylosing spondylitis (AS) have been limited to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and to some traditional disease modifying drugs (DMARDs) such as sulfasalazine and methotrexate. In view of open label and controlled trials of treatment with a monoclonal chimeric tumour necrosis factor (TNF) α antibody (infliximab), and with recombinant human TNF receptor (etanercept), the need for more effective second line treatments in AS seems to be met.1–4
In this study we aimed at determining the proportion of patients with active AS, despite treatment with NSAIDs and second line treatments (sulfasalazine, methotrexate), using current guidelines for anti-TNF treatment in a tertiary clinical care.
METHODS AND RESULTS
Study patients were selected according to the Modified New York criteria. ASAS and SPARTAN guidelines for biological treatments of AS were used.5,6 Ninety three patients with AS (M/F = 46/47, mean (SD) age 39.5 (11.5) years, mean (SD) disease duration 13.7 (10.5) years) were screened. The University of Marmara Institutional review board approved the study and informed consent was given by the study patients.
Eighty patients (86%) were receiving NSAIDs: 67/93 (72%) sulfasalazine and 32/93 (34%) methotrexate. Disease duration, age, disease activity defined by the Bath AS Disease Activity Index (BASDAI), and drugs used did not differ significantly between male and female patients. Of the 93 patients, 32 (34%; M/F = 17/15) and 37 patients (40%; M/F = 18/19) were defined as having active AS according to SPARTAN and ASAS guidelines, respectively.
Although high mean C reactive protein (CRP) values are considered critical in defining active AS, the higher mean CRP values detected in the male patients (male v female mean CRP, 259 v 69 mg/l, p = 0.054) did not correlate with the ratio of men and women considered to have active AS (ASAS = 18M/19F, SPARTAN = 17M/15F). Higher CRP values in this group correlated negatively with the use of sulfasalazine (r = −0.764, p = 0.05).
Our study showed that a significant number of patients had active AS (34–40%) in our patient tertiary care clinic. A recent study reflects the same need for effective treatment in AS, though that study had a higher proportion of patients with active AS (65%).7 In that study, NSAIDs were used as the first line treatment option and use of sulfasalazine and methotrexate was limited. We used combined methotrexate with sulfasalazine for persistent peripheral arthritis, which might have had modifying effects on disease activity in our study group, despite a lack of evidence that conventional DMARDs alter the course of established axial disease, and might explain the differences between the two studies.
According to current diagnostic criteria, patients with AS must have x ray changes for the diagnosis, which take months to years to establish. Two separate studies from Europe emphasise that a substantial period of active disease was already present before the diagnosis.8,9 As we now know, treatment with biological agents improves the signs and symptoms of axial disease in AS where traditional DMARDs fail.1–4 Starting DMARDs at an earlier stage of AS after the diagnosis might provide a chance to assess the effect of conventional treatment in patients with shorter disease duration and enable use of anti-TNF treatment for patients with refractory disease before the radiographic signs of established disease occur.
In a similar study of rheumatoid arthritis10 the eligibility of patients receiving routine care to receive treatment with TNFα agents, according to the inclusion criteria of the studies for biological agents, was also low (prevalence of 8%). However, current criteria for defining patients with active AS eligible for anti-TNF treatment, and patient selection criteria of major clinical trials with biological agents, do parallel each other, suggesting that current guidelines for selecting patients with active AS are suitable for routine clinical care.
In conclusion, a significant subset of the patients with AS followed up in our tertiary care clinic require more effective treatment according to current guidelines despite intensive conventional second line treatment.