Send letter to journal:
Re: Comment on "ASAS/EULAR recommendations for the management of ankylosing spondylitis "

Dear Editor,

The ASAS/EULAR group who recently published 10 key recommendations for the management of ankylosing spondylitis (AS) based on the combination of research based evidence and expert consensus, should be commended for their collaborative work [1]. However, it should be noted that they provide grading of strength of recommendation (SOR) for the specific treatment options, but not for the key recommendations. In their report, the grading of SOR was done on the traditional A-D scale by two members of the committee and also on a 0-10 numerical scale by all of the members. Although a grade A level SOR for use of a specific treatment modality is likely to generate a high value on the numerical scale, the experts in the committee could give it a relatively low value based on safety, cost- effectiveness and clinical expertise which were not taken into consideration in the alphabetical scale (i.e misoprostol, SOR: grade A on A-D scale; 5.55 on numerical scale). However, when the recommendation is against the use of a specific treatment option, grade A level SOR based solely on efficacy should most likely yield a low value on the numerical scale (i.e methotrexate, SOR: grade A on A-D scale; 3.14 on numerical scale) which makes it difficult to correlate the ratings on the two scales which actually had different meanings. SOR of a given treatment modality on the traditional A-D scale indicated the level of confidence on the recommendation which may be for or against its use in the management of AS, whereas SOR on the numerical scale indicated how strongly experts recommended the use of that treatment modality since they seem to have been asked how strongly they would recommend the use of each treatment option based on efficacy, safety, cost effectiveness and clinical expertise (0 meant, not recommended at all; 10 meant fully recommended). To make the ratings by two approaches more comparable, the experts should rather have been asked how strongly they would support the recommendation for or against the use of each specific treatment based on efficacy, safety, cost effectiveness and clinical expertise. It is mentioned in table 6 as well as in the text, that available level Ib evidence for the efficacy of sulfasalazine (SSZ) in AS are inconclusive. Then, it is difficult to understand what the grade A SOR for SSZ in this table signifies. Any inconclusive studies of any level can probably generate only Grade D recommendations according to Center for Evidence Based Medicine [2]. Evidence level for efficacy of SSZ and SOR for its use should probably have been assessed separately for axial and peripheral disease.

The ASAS/EULAR group categorized the evidence for the studies [3-5] with intravenous pulse corticosteroids as level IV and rated the SOR for its use as grade D. Two of these studies were small single group pre-post studies with favorable results [3, 4]. The other was a dose-response double blind study which showed a quick and long lasting effect on pain, spinal mobility and morning stiffness in both doses [5]. Thus, this can also be considered as a pre-post study which should be categorized as quasi experimental study (Level IIb evidence) and that is probably why the SOR for the use of intravenous pulse steroids was rated as grade B on an A-C scale (according to the recommendations of AHCPR 1994) in another consensus report [6], which should correspond to B or C on the traditional A-D scale that was used in the ASAS/EULAR recommendations. Evidence based guidelines and recommendations developed by panels of experts are of major help to clinicians who are often unaware of the available evidence or fail to assess the evidence on the right principles, for integrating the best available evidence into their day to day decision making. To be able to achieve that, they should communicate concise, clear and specific messages to the users and also provide them with information on how much confidence they can have in following those recommendations. However, the clarity of at least some of the recommendations published by the ASAS/EULAR group is not quite up to that standard, and the article later published for further clarification by some of the authors of the original paper [7] does not appear to have improved it, greatly.

References

1. Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2006;65:442-52.

2. Centers for evidence based Medicine: Levels of Evidence and Grades of Recommendation. http://www.cebm.net/levels_of_evidence.asp (Last Accessed Feb 14, 2006).

3. Mintz G, Enriquez RD, Mercado U, et al. Intravenous methylprednisolone pulse therapy in severe ankylosing spondylitis. Arthritis Rheum. 1981;24:734-6.

4. Richter MB, Woo P, Panayi GS, et al. The effects of intravenous pulse methylprednisolone on immunological and inflammatory processes in ankylosing spondylitis. Clin Exp Immunol. 1983;53:51-9.

5. Peters ND, Ejstrup L. Intravenous methylprednisolone pulse therapy in ankylosing spondylitis. Scand J Rheumatol. 1992;21:134-8.

6. Maksymowych WP, Inman RD, Gladman D, et al. Canadian Rheumatology Association Consensus on the use of anti-tumor necrosis factor-alpha directed therapies in the treatment of spondyloarthritis. J Rheumatol. 2003;30:1356-63.

Send letter to journal:
Re: Looking for evidence for established facts?

Dear Editor

we read with interest recommendations for the management of ankylosing spondylitis by Zochling J et al (1). The autors made huge efforts to find and analise literature but final results seems to be questionable have these efforts been needed. In the recommendations we can see only one new treatment approach to the patients with ankylosing spondylitis (AS). Rheumatologists around the world many years ago accepted tailored approach to the treatment of AS according to individal basis. Looking for evidence for established therapeutic modalities in AS like the use of non-pharmacological and pharmacological treatment and their combination (2) leeds to looking evidence ad apsurdum. Education, physical therapy and exercises are the parts of routine management of AS and the choice of non steroidal anti-inflammatory drugs (NSAIDs) as first line drugs therapy is also notorious fact. In pharmacological treatment of musculoskeletal diseases is generaly accepted use of paracetamol and opioids for pain control in patients in whom NSAIDs are contraindicated or poorly tolerated. Corticosteroids localy adminstered are also well known therapeutic choice and knowledge that systemic application of corticosteroids particularly for axial disease is of limited value is preaty clear. Poor results with DMARDs for control of disease except peripheral arthritis is also well known. The hip arthroplasty when indicated should not be commented. Controversy about spinal surgery still exists. Only one new approach is recommended – anti-TNF therapy. Despite, the autors suggest positive side of anti TNF therapy (rapid onset of clinical effect for spinal pain, function and peripheral joint disease) the high risk of serious adverse events (infection, demyelinating disease, heart failure et cetera) and high cost are limiting factor for the use of these compounds.Do the efficacy of this therapy realy outweigh the high cost and safety ? Brandt J et al reported that 75 % of AS patients experienced a relapse at a mean of 6 weeks an almost all patients experienced relapse 24 weeks after stopping etanercept (3). Is realy appropriate to treat spinal pain and function with biologic agents? Long- term data of safety and efficacy of these compounds are scarce and we not known do the biological agents are true disease modification drugs meaning retardation or arrest of progressive and ireversibile structural damage or blocking inflammation agents without interfering with the underlying patophysiological mechanisms that lead to ankylosis in AS (4)? In other side we have suggestions that nonsteroidal anti-inflammatory drugs in continuous use can reduce radiographic progression in patients with AS (5).The principles of evidence based medicine are well accepted in the field of rheumatology but should the well established facts be realy proved?

References

1.Zochling J, Van der Heijde D, Burgos-Vargas R et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis piublished online 26 Aug 2005;doi:10.1136/ard.2005.041137.

2.Otto W, Tautenhahn B, Hantzschel H, Romhild N. Therapy of ankylosing spondylitis. Z Gesamte Inn Med 1977;32:343-347.

3.Brandt J, Khariouzov A, Listing J et al. Six-month results of a double blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum 2003;48:1667-1675.

4.Van den Bosch F, De Keyser F, Mielants H, Veys ME. Tumor necrosis factor -á blockade in ankylosing spondylitis : a potent but expansive anti- inflammatory treatment or true disease modification ? Arthritis Res ther 2005;7:121-123.

5.Wanders A, Van der Heijde D, Landewe R et al. Nonsteroidal anti- inflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis. Arthritis Rheum 2005;52:1756-1765.