Active axSpA Research Articles

Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction

BackgroundThe best strategy for maintaining clinical remission in patients with axial spondyloarthritis (axSpA) has not been defined. C-OPTIMISE compared dose continuation, reduction and withdrawal of the tumour necrosis factor inhibitor...

The impact of certolizumab pegol treatment on the incidence of anterior uveitis flares in patients with axial spondyloarthritis: 48-week interim results from C-VIEW

BackgroundAcute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). C-VIEW investigates the impact of the Fc-free TNF inhibitor certolizumab pegol (CZP) on AAU...

Study to Demonstrate the Efficacy, Safety and Tolerability of an Intravenous Regimen of Secukinumab Compared to Placebo in Subjects With Active axSpA

Study to Demonstrate the Efficacy, Safety and Tolerability of an Intravenous Regimen of Secukinumab Compared to Placebo in Subjects With Active axSpA

Short term effect of non-steroidal anti-inflammatory drugs on clinical and magnetic resonance imaging of the sacroiliac joints progression in axial spondyloarthritis patients

Aim of the workTo evaluate the short term effect of maximally tolerated dose of non-steroidal anti-inflammatory drugs (NSAIDs) on disease activity and radiographic progression of axial spondyloarthritis (axSpA) patients. Patients and methodsA six-week prospective study on thirty patients with active axSpA. All patients were assessed at baseline visit, a follow-up visit after 2 weeks, and 6 weeks of treatment with a maximally tolerated dose of NSAID. Disease activity was assessed by determining Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), and functional assessment by using Bath Ankylosing Spondylitis Functional Index (BASFI). Spinal mobility was assessed by the mean improvement in Bath Ankylosing Spondylitis Metrology Index (BASMI). Magnetic Resonance Imaging (MRI) of sacroiliac joints (SIJs) was taken at baseline and at the end of the study and was evaluated according to Berlin scoring method. ResultsImprovement in laboratory activity markers and all disease activity scores has been observed at week 6 of maximally tolerated dose of NSAIDs which were significant (p < 0.001). Additionally, ASDAS clinically important improvement was achieved in 63.3% of patients, and BASDAI50 was achieved in 30% and 56.7% of patients at week 2 and week 6, respectively. Furthermore, Berlin score showed an improvement by 14.2% with a reduction in bone marrow edema signal intensity of SIJs in 40% of patients. ConclusionIn Egyptian cohort of patients with axSpA, intake of maximally tolerated dose of NSAID could improve the health-related quality of life, disease activity scores, and sacroiliac joint inflammation on MRI.

A New Medical Therapy for Axial Spondyloarthritis

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the first choice of treatment for axial spondyloarthritis (axSpA); cyclooxygenase (COX)-2 inhibitors reduce both inflammation and bone formation. When NSAID treatment fails, tumor necrosis factor inhibitors (TNFis) can be used to treat active axSpA, but, presently, TNFis cannot completely prevent radiographic progression. Theoretically, as TNF is a strong pro-inflammatory cytokine triggering bone resorption, TNFis should stimulate bone formation. Recently, it was discovered that the IL-23/-17 axis is associated with enthesitis development and bone formation in a mouse model. The anti-IL-23 monoclonal antibody ustekinumab has been approved as treatment for moderate-to-severe plaque psoriasis and psoriatic arthritis. However, in axSpA patients, ustekinumab effectiveness was low and a phase 3 clinical trial was terminated. The anti-IL-17A monoclonal antibody secukinumab has been approved as treatment for moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In a 3-year extension of the MEASURE 1 observational study, the mean change in modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) from baseline to week 104 was 0.30 ± 2.53 among patients with evaluable X-rays originally randomized to secukinumab (n = 168). Such patients exhibited less radiographic progression compared to other TNFi studies. Several new drugs are in clinical trials exploring their effects on axSpA; these include ixekizumab (an anti-IL-17A monoclonal antibody), brodalumab (an anti-IL-17 receptor monoclonal antibody), and the Janus kinase (JAK) inhibitors tofacitinib and upadacitinib. The IL-23/-17 axis is important in terms of axSpA inflammation and bone formation. However, to date, no drug has completely prevented radiographic progression in axSpA patients. Keywords: Spondyloarthritis; Ankylosing; Ankylosing spondylitis; Medicine 중심 단어: ì²™ì¶”ê´€ì ˆì—¼; 강직; 강직척추염; 약물

Divergent effects on macrophage biomarkers soluble CD163 and CD206 in axial spondyloarthritis

The chronic joint inflammation in axial spondyloarthritis (axSpA) is characterized by infiltration of activated macrophages. The haptoglobin–hemoglobin receptor CD163 and the mannose receptor CD206 are strongly expressed on M2c and M2a macrophages, respectively. We measured the soluble forms of the receptors (sCD163 and sCD206) in plasma (PL) in two axSpA cohorts. All patients fulfil the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA and/or the 1984 modified New York criteria for ankylosing spondylitis. The first cohort included anti-TNF-α treated patients with active axSpA (n = 30); the second cohort included patients in early disease stages (n = 38). Plasma sCD163 and sCD206 were both within the reference interval of healthy controls (HC), but sCD163 decreased slightly during anti-TNF-α treatment [baseline: 1.49 mg/L (IQR: 1.22–1.77 mg/L, 12 weeks: 1.29 (IQR: 1.09–1.57) mg/L, 20 weeks: 1.25 (IQR: 0.99–1.75) mg/L, 52 weeks: 1.39 (IQR: 1.15–1.78) mg/L], while sCD206 increased [baseline: 0.17 (IQR: 0.13–0.21) mg/L, 12 weeks: 0.19 (0.16–0.23) mg/L, 20 weeks: 0.20 (0.14–0.24) mg/L, 52: 0.19 (IQR: 0.14–0.23) mg/L], pointing toward a shift in polarization of involved macrophages. Plasma levels of sCD206 proved significantly higher in patients with early disease stages and definite radiological sacroiliitis (n = 10). This was not the case for sCD163. A significant increase in response to anti-TNF-α treatment, could suggest sCD206 as a marker of response to anti-TNF-α treatment, however, the potential for the two macrophage markers as diagnostic and prognostic indicators of disease in axSpA is weak.

New treatment targets for axial spondyloarthritis.

Axial spondyloarthritis (axSpA) patients can be divided into those with structural damage in the SI joint visible on X-rays, termed radiographic axSpA or AS, and those in an earlier phase of the disease, without structural damage in the SI joint, termed non-radiographic axSpA. TNF-blockers have been shown to be highly effective in the treatment of active axSpA. Interestingly, conventional DMARDs and also non-TNF-blocker biologics targeting IL-1, IL-6 and T cells (abatacept) are not effective. Recent interest has focused on the cytokines IL-23 and IL-17 as potential treatment targets in axSpA. An open-label trial with ustekinumab showed a good efficacy in AS patients. Two placebo-controlled phase 3 trials with a mAb blocking IL-17, secukinumab, showed a good reduction in disease activity, similar to that shown for TNF blockers. Probably triggered by inflammation, new bone formation is another hallmark in AS and a potentially important treatment target. However, a previously reported inhibitory effect of NSAID treatment could not be confirmed in a recent NSAID trial.

Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study.

BackgroundPhysical therapy is recommended for the management of axial spondyloarthritis (axSpA) and flexibility exercises have traditionally been the main focus. Cardiovascular (CV) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases. Therefore, the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA.MethodsIn a single blinded randomized controlled pilot study the exercise group (EG) performed 12 weeks of endurance and strength exercise while the control group (CG) received treatment as usual. The primary outcome was the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS). Secondary outcomes included patient reported disease activity (Bath AS Disease Activity Index [BASDAI]), physical function (Bath AS Functional Index [BASFI]), and CV risk factors measured by arterial stiffness (Augmentation Index [Alx]) and Pulse Wave Velocity [PWV]), cardiorespiratory fitness (VO2 peak) and body composition. ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences, and Mann Whitney U-test was used for outcomes with skewed residuals.ResultsTwenty-eight patients were included and 24 (EG, n = 10, CG, n = 14) completed the study. A mean treatment effect of −0.7 (95%CI: −1.4, 0.1) was seen in ASDAS score. Treatment effects were also observed in secondary outcomes (mean group difference [95%CI]): BASDAI: −2.0 (−3.6, −0.4), BASFI: −1.4 (−2.6, −0.3), arterial stiffness (estimated median group differences [95% CI]): AIx (%): −5.3 (−11.0, −0.5), and for PVW (m/s): −0.3 (−0.7, 0.0), VO2 peak (ml/kg/min) (mean group difference [95%CI]: 3.7 (2.1, 5.2) and trunk fat (%): −1.8 (−3.0, −0.6). No adverse events occurred.ConclusionHigh intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial.Trial RegistrationClinicalTrials.gov NCT01436942

SAT0362 Certolizumab Pegol Rapidly Reduces Peripheral Enthesitis and the Incidence of Tender and Swollen Joints in Patients with Active Axial Spondyloarthritis, Including Both Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis

BackgroundAxial spondyloarthritis (axSpA) is characterized by inflammation of the spine. However, the disease can also be associated with extra-spinal manifestations such as inflammation of the entheses (enthesitis) and peripheral joints,...

SAT0351 Long-Term Safety and Efficacy of Certolizumab Pegol in Patients with Axial Spondyloarthritis, Including Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis: 96-Week Outcomes of the Rapid-Axspa Trial

BackgroundPrevious reports of RAPID-axSpA (NCT01087762) demonstrated efficacy and safety of certolizumab pegol (CZP) in patients (pts) with axial spondyloarthritis (axSpA) including pts with ankylosing spondylitis (AS) and pts with non-radiographic...

SAT0355 Observed Incidence Rates of Uveitis following Certolizumab Pegol Treatment in Patients with Axial Spondyloarthritis

BackgroundAxial spondyloarthritis (axSpA) is characterized by inflammation in the spine and sacroiliac joints, but can also manifest as inflammation at extra-spinal sites, most commonly inflammation of the uvea (uveitis).1ObjectivesTo estimate...

SAT0357 Evaluation of the Nonsteroidal Anti-Inflammatory Drug-Sparing Effect of Etanercept in Axial Spondyloarthritis: Results of the Multicenter Randomized, Double-Blind, Placebo-Controlled SPARSE Trial

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are first-line pharmacotherapy in axial spondyloarthritis (axSpA) but are recommended for use at the lowest effective dose for the shortest possible time due to safety concerns....

Discriminant validity, responsiveness and reliability of the arthritis-specific Work Productivity Survey assessing workplace and household productivity within and outside the home in patients with axial spondyloarthritis, including nonradiographic axial spondyloarthritis and ankylosing spondylitis.

IntroductionThe arthritis-specific Work Productivity Survey (WPS) was developed to evaluate productivity limitations associated with arthritis within and outside the home. There is an unmet need for an instrument assessing similar productivity limitations in axial spondyloarthritis (axSpA), including nonradiographic axSpA and ankylosing spondylitis. Following its validation in rheumatoid and psoriatic arthritis, we aimed to assess psychometric properties of WPS in adult-onset active axSpA in this analysis.MethodsPsychometric properties were assessed using data from the RAPID-axSpA trial (NCT01087762) in which researchers investigated certolizumab pegol efficacy and safety in axSpA. WPS was completed at baseline and every 4 weeks until week 24. Validity was evaluated at study baseline via known-groups defined by the first and third quartile cutoffs of patient scores to Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain, Bath Ankylosing Spondylitis Functional Index (BASFI), Short Form 36 health survey (SF-36) and Ankylosing Spondylitis Quality of Life Scale (ASQoL). Responsiveness and reliability were assessed by comparing WPS mean changes in ASAS 20% improvement criteria (ASAS20), BASDAI50, ASDAS clinically important improvement/major improvement (CII/MI) and BASFI minimum clinically important difference (MCID) responders versus nonresponders at week 12. All comparisons were conducted on observed cases in the randomized set using a nonparametric bootstrap-t method.ResultsThe results confirmed the psychometric properties of WPS. AxSpA patients with a worse health state had significantly more days of household work lost, household work with reduced productivity, social activities missed and outside help hired, as well as a higher interference rate of arthritis, than patients with a better health state. Similarly, employed patients with a worse health state had significantly more work days lost or with productivity reduced, and a higher interference of arthritis on work productivity. Similar findings were also observed in the nonradiographic (nr) axSpA and AS subpopulations. The WPS was responsive to clinical changes, with responders reporting larger improvements at week 12 in WPS scores versus nonresponders. Effect sizes in responders were generally moderate to large (standardized response mean >0.5).ConclusionsThese analyses demonstrate that WPS is a valid, responsive and reliable instrument for the measurement of productivity within and outside the home in adult-onset axSpA, as well as the in subpopulations of AS and nr-axSpA.Electronic supplementary materialThe online version of this article (doi:10.1186/ar4680) contains supplementary material, which is available to authorized users.

Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study

ObjectivesTo evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with...

FRI0439 High economic burden of axial spondyloarthritis related to paid work and household productivity at baseline in the rapid-axspa study: differences and similarities between ankylosing spondylitis and non-radiographic axial spondyloarthritis

BackgroundAxial spondyloarthritis (axSpA) includes both ankylosing spondylitis (AS) and axSpA with no definitive sacroiliitis on X-ray (non-radiographic axSpA, nr-axSpA). AS significantly affects patients’ (pts) work productivity,1 however, there is no...

THU0360 Rapid Improvements in Patient-Reported Outcomes with Certolizumab Pegol in Patients with Axial Spondyloarthritis, Including Ankylosing Spondylitis: 24-Week Results of Rapid-Axspa Study

BackgroundAxial spondyloarthritis (axSpA) includes both ankylosing spondylitis (AS) and axSpA with no definitive sacroiliitis on X-ray (non-radiographic axSpA, nr-axSpA). These patients (pts) subgroups have similar clinical disease burden,1 however, the...

OP0106 Effect of Certolizumab Pegol on Signs and Symptoms of Axial Spondyloarthritis, Including Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis: 24-Week Results of Rapid-Axspa Study

BackgroundAxial spondyloarthritis (axSpA) includes both ankylosing spondylitis (AS) and axSpA with no definitive sacroiliitis on X-ray (non-radiographic axSpA, nr-axSpA). RAPID-axSpA (NCT01087762) is the first RCT of an anti-TNF to include...

OP0107 Improvements in Work and Household Productivity after 24 Weeks of Certolizumab Pegol in Treatment of Axial Spondyloarthritis Patients, Including Patients with Ankylosing Spondylitis: Results of Rapid-Axspa Study

BackgroundAxial spondyloarthritis (axSpA) includes both ankylosing spondylitis (AS) and axSpA with no definitive sacroiliitis on X-ray (non-radiographic axSpA, nr-axSpA). AS significantly affects patients’ (pts) work productivity.1 The impact of the...

FRI0419 Effect of certolizumab pegol on inflammation of spine and sacroiliac joints in patients with axial spondyloarthritis: 12-week magnetic resonance imaging results of rapid-axspa study

BackgroundAxial spondyloarthritis (axSpA) includes both ankylosing spondylitis (AS) and axSpA with no definitive sacroiliitis on X-ray (non-radiographic axSpA, nr-axSpA).1 One of the features of axSpA is bone marrow edema of...

Axial spondyloarthritis: is there a treatment of choice?

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). Nonradiographic axSpA (axSpA without radiographic sacroiliitis) and ankylosing spondylitis (AS; radiographic form of axSpA) are considered nowadays as two consecutive stages of one disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective against the major symptoms of axSpA (pain and stiffness) and may have disease-modifying properties including retarding progression of structural damage in the spine. Therefore, NSAIDs, unless contraindicated, are the treatment of choice for the majority of patients with axSpA. Beyond NSAIDs, only tumour necrosis factor (TNF) α blockers are effective and approved for the treatment of active axSpA. Several novel drugs (i.e. monoclonal antibodies targeting interleukin-17, interleukin-12/23, inhibitors of phosphodiesterase-4 and kinases), which might be effective in axSpA, are currently under investigation. Pharmacological therapy of axSpA should always be combined with nonpharmacological treatment including education and regular exercise/physiotherapy.