This is a good 'general' paper: EULAR and ASAS research aired-
http://thejns.org/doi/pdf/10.3171/FOC/2008/24/1/E4Medical management of ankylosing spondylitisALEXANDER A. KHALESSI, M.D., M.S.,1BRYAN C. OH, M.D.,1 AND MICHAEL Y. WANG, M.D.2
1Department of Neurological Surgery, University of Southern California, Los Angeles, California;
and 2Department of Neurological Surgery, University of Miami, Florida
"PIn the following literature review the authors consider the available evidence for the medical management of patients
with ankylosing spondylitis (AS), and they critically assess current treatment guidelines. Medical therapy for axial disease
in AS emphasizes improvement in patients’ pain and overall function.
First-line treatments include individualized physical therapy and nonsteroidal antiinflammatory drugs (NSAIDs) in conjunction with gastroprotective therapy. After an adequate trial of therapy with two NSAIDs exceeding 3 months
or limited by medication toxicity, the patient may undergo tumor necrosis factor–a blockade therapy. Response should occur within 6–12 weeks, and patients must undergo tuberculosis screening. Evidence does not currently support the use"
(snip...) "
Nonsteroidal antiinflammatory drug and coxib toxicity profiles center around gastrointestinal and cardiovascular complications. Nonsteroidal antiinflammatory drugs confer a dose-dependent increased risk of gastrointestinal bleeding (RR 5.36, 95% CI 1.79–16.10). Gastroprotective agents such as misoprostol, H2 blockers, and proton-pump inhibitors mitigate this risk (RR 0.40, 95% CI 0.03–0.74).Coxibs pose a lower overall risk of serious gastrointestinal toxicity but are associated with considerable diarrhea and dyspeptic symptoms. [color:#993399][b](Don't tell me about it, exactly as you warned me those many years ago Mig. Horrible: exacerbated RefluxGERD)[/b][/color] Coxibs further carry an increased risk of thromboembolic complications such as myocardial infarction or stroke. Relative risks of rofecoxib 2.30 (95% CI 1.22–4.33), valdecoxib 3.7 (95% CI 1.0–13.5) and naproxen 2.0 (no CI available) bear out this class effect.
Data regarding the cardiovascular complications of NSAID use are under investigation.15 According to the ASAS/EULAR guidelines, NSAIDs are therefore the first-line drug treatment for AS patients with pain and stiffness.
In the face of increased gastrointestinal
risks, either a nonselective NSAID plus a gastroprotective
agent, or a selective cyclooxygenase-2 inhibitor should be used. Evidence does not currently support the use
of local or systemic corticosteroid therapy in patients with
AS spinal disease. Class Ib evidence exists that local corticosteroid injections may provide short-term palliation of
sacroiliitis symptoms (ES 1.92, 95% CI 0.53–3.35) and Class IV evidence supports local steroid injections for enthesitis.16"
(snip...) "
Disease-Modifying Antirheumatic Drugs Sulfasalazine and methotrexate represent the most widely used DMARDs. Individual Cochrane reviews exist regarding the utility of these agents in the treatment of AS.
Unfortunately,
neither agent meaningfully modifies pain or functionality attributable to AS spinal disease.4,5 Eleven randomized trials examined sulfasalazine use in patients with AS and contributed to the Cochrane metaanalysis. 6 Although erythrocyte sedimentation rate (mean –4.79, 95% CI –8.80 to –0.78) and morning stiffness
(–13.89 on a 100-point visual analog scale; 95% CI –22.54
to –5.24) improved significantly with sulfasalazine, back
pain (ES –2.38, 95% CI –5.78 to 1.03) and physical function
(ES 0.20, 95% CI –0.77 to 1.18) did not improve. Moreover,
common toxicities (RR 2.37 for adverse event,
95% CI 1.58–3.55) include gastrointestinal symptoms, mucocutaneous, hepatic, or hematological manifestations.13
The Cochrane review of methotrexate examined 116 patients with AS across 3 trials and found no significant improvements in BASDAI or BASFI. Pooled results for spinal pain (ES –0.05, 95% CI –0.48 to 0.38) and function (ES 0.02, 95% CI –0.40 to 0.45) failed to achieve statistical significance relative to placebo.
Methotrexate toxicities
included nausea (RR 2.12, 95% CI 1.50–2.98) and hepatic
abnormalities (RR 4.12, 95% CI 2.22–7.63). In an observational
study of 14 patients, the authors estimated that 21% of patients taking methotrexate must stop the drug due to toxicity.4Bisphosphonates and thalidomide remain other areas of open DMARD investigation in AS. Maksymowych et al.14 published a Class III study involving high-dose pamidronate and reported significantly improved function (ES
0.73, 95% CI 0.29–1.17) and axial pain (p = 0.003).
Anecdotal evidence supports the use of thalidomide for axial pain, but current ASAS/EULAR guidelines found thalidomide’s
toxicity profile prohibitive.15The DMARDs, including sulfasalazine and methotrexate, therefore do not currently enjoy empirical support for their use in axial AS disease. Sulfasalazine may have a limited
role in treatment of peripheral joint symptoms.5 Tumor Necrosis Factor and Interleukin Inhibitors."
(snip...) anti-TNF THerapy: "inhibitors is rapid, and the therapeutic effect persists for 3 years with continuing treatment. Treatment cessation results in a high incidence of relapse. Due to the rapid onset, ASAS/EULAR established a 6–12-week time frame to Neurosurg. Focus / Volume 24 / January 2008
Medical management in ankylosing spondylitis3 identify nonresponders and terminate therapy.15 The need for rapid identification of patients with AS not experiencing the benefits of TNFa blockade is to spare the patient any therapeutic risks.14
The TNFa inhibition increases the patient’s susceptibility to common upper respiratory infections and tuberculous disease; screening for Mycobacterium tuberculosis is now a prerequisite for therapy initiation. Infliximab may precipitate a positive antinuclear antibody titer, and the incidences of demyelinating disease and lupuslike syndromes, although anecdotally reported, remains unknown.2" (more...)
I left in some extra info as it was very interesting and of course pertinent to treatment of AS!
(Apologies - tried to do summat about the line endings, but didn't work! Always diff when dealing with columnar input...!)
