https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)08215-6.pdf

Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial

To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

https://ard.bmj.com/content/annrheumdis/76/6/978.full.pdf

2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis

This fi rst up date of the ASAS/EULAR recommendations on the management of anky lo sing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in de tail and rewor ded if necessary. Decisions on new re com men da tions were made — if necessary after voting. The strength of the recommen dations (SOR) was scored on an 11-point nume rical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfi ll the modifi ed NY criteria for AS, independent of extra-ar ticu lar manifestations, and they take into ac count all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points in clu ding 2 new ones, one related to extra-articular manife sta tions and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good.

/pdf/2010-update-of-the-asas-eular-recommendations-for-the-3t8xq4bpzg.pdf

2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis

2010 Update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis

Objective
To evaluate the safety and efficacy of adalimumab, a fully human recombinant IgG1 monoclonal antibody that specifically targets human tumor necrosis factor, in patients with active ankylosing spondylitis (AS).

Methods
This was a multicenter, randomized (2:1 ratio), double-blind, placebo-controlled study to evaluate a subcutaneous injection of adalimumab, 40 mg every other week, compared with placebo for 24 weeks. The primary efficacy end point was the percentage of patients with a 20% response according to the ASsessment in Ankylosing Spondylitis International Working Group criteria for improvement (ASAS20) at week 12. Secondary outcome measures included the ASAS20 at week 24 and multiple measures of disease activity, spinal mobility, and function, as well as ASAS partial remission.

Results
At week 12, 58.2% of adalimumab-treated patients (121 of 208) achieved an ASAS20 response, compared with 20.6% of placebo-treated patients (22 of 107) (P < 0.001). More patients in the adalimumab group (45.2% [94 of 208]) than in the placebo group (15.9% [17 of 107]) had at least a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index at week 12 (P < 0.001). Significant improvements in the ASAS40 response and the response according to the ASAS5/6 criteria at weeks 12 and 24 were also demonstrated (P < 0.001). Partial remission was achieved by more adalimumab-treated patients than placebo-treated patients (22.1% versus 5.6%; P < 0.001). Adalimumab-treated patients reported more adverse events (75.0% versus 59.8% of placebo-treated patients; P < 0.05), but there was no statistically significant difference in the incidence of infections. Most adverse events were mild or moderate in severity.

Conclusion
Adalimumab was well-tolerated during the 24-week study period and was associated with a significant and sustained reduction in the signs and symptoms of active AS.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.21913

Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: A 2-year randomized controlled trial was performed to test the hypothesis that long-term, continuous treatment with nonsteroidal antiinflammatory drugs (NSAIDs), in comparison with NSAID treatment on demand only, influences radiographic progression in patients with ankylosing spondylitis (AS). METHODS: Patients with AS (n = 215), who had previously participated in a 6-week, randomized, double-blind clinical trial that compared celecoxib, ketoprofen, and placebo, were randomly allocated to receive either continuous treatment with NSAIDs or on-demand treatment with NSAIDs for a period of 2 years. All patients began treatment with celecoxib, at a starting dosage of 100 mg twice daily; patients could increase this dosage to 200 mg twice daily or could switch to another NSAID while maintaining the same treatment strategy. Structural changes were assessed by radiographs of the lumbar and cervical spine and scored according to the modified Stoke Ankylosing Spondylitis Spine Score by one observer who was blinded to the treatment strategy and temporal order of the radiographs. Statistical analyses included a between-group comparison of 1) radiographic progression scores (by Mann-Whitney U test), 2) time-averaged values of variables reflecting signs and symptoms of AS (by linear regression analysis), and 3) the frequency of reported site-specific adverse events (by chi-square test or Fisher's exact test, as appropriate). RESULTS: Complete sets of radiographs were available for 76 of the 111 patients in the continuous-treatment group and for 74 of the 104 patients in the on-demand group. The mean +/- SD scores for radiographic progression were 0.4 +/- 1.7 in the continuous-treatment group and 1.5 +/- 2.5 in the on-demand treatment group (P = 0.002). Parameters reflecting signs and symptoms were not statistically significantly different between groups. The between-group difference in radiographic progression did not disappear after adjusting for baseline values of radiographic damage or disease activity variables and for time-averaged values of disease activity variables, nor after input of missing data. Relevant adverse events tended to occur more frequently in the continuous-treatment group than in the on-demand group (for hypertension, 9% versus 3%; for abdominal pain, 11% versus 6%; for dyspepsia, 41% versus 38%), but the differences were not statistically significant. CONCLUSION: A strategy of continuous use of NSAIDs reduces radiographic progression in symptomatic patients with AS, without increasing toxicity substantially.

/pdf/nonsteroidal-antiinflammatory-drugs-reduce-radiographic-269hw8zqkf.pdf

Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: A randomized clinical trial

Objective

To evaluate the short-term efficacy of celecoxib, a cyclooxygenase 2–specific inhibitor, in the treatment of ankylosing spondylitis (AS).



Methods

The study was a 6-week randomized, double-blind, placebo-controlled trial with 3 treatment arms: placebo, ketoprofen 100 mg twice daily, and celecoxib 100 mg twice daily. Patients who had AS according to the modified New York criteria, without peripheral synovitis and with active disease (pain ≥40 mm on a 100-mm visual analog scale [VAS] and an increase in pain of at least 30% after nonsteroidal antiinflammatory drug withdrawal) were eligible for study. Primary outcome measures were change in pain intensity (VAS) and change in functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI]).



Results

Of the 246 randomized patients, 76 were allocated to receive placebo, 90 ketoprofen, and 80 celecoxib. There were no statistically significant differences between treatment groups at study entry. During the 6 weeks of the study, the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group, with a trend in favor of celecoxib when the 2 active treatments were compared. The mean changes were −13 mm, −21 mm, and −27 mm (P = 0.006) for pain and 1, −6, and −12 (P = 0.0008) for BASFI score in the placebo, ketoprofen, and celecoxib groups, respectively. During treatment, the number of patients reporting epigastric pain was 6 (8%), 13 (14%), and 10 (13%) in the placebo, ketoprofen, and celecoxib groups, respectively.



Conclusion

The results of this study confirm the clinically relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage, with significant improvement of both pain and function in patients with AS.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1529-0131%28200101%2944%3A1%3C180%3A%3AAID-ANR24%3E3.0.CO%3B2-K

Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug.

Jehan‐Michel Béhier

Papers

Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: A randomized clinical trial

Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug.