Therapy In Axial Spondyloarthritis Research Articles

A Randomized Controlled Trial of Dose Reduction of Biologic Therapy in Axial Spondyloarthritis: Rationale and Protocol of an Open-Label Non-inferiority Study and a Review of Literature

Axial spondyloarthritis (SpA) is a spectrum of inflammatory conditions predominantly involving the spine and sacroiliac (SI) joints. The development of biological therapies has revolutionized the treatment paradigm in SpA. This has led to a great improvement in clinical outcomes, including inflammation suppression, symptom alleviation, and functional improvement. Despite its usefulness, the question regarding the optimal duration of therapy remains unanswered. This is particularly important given the cost associated with biological therapies, and the potential side effects related to immune suppression. Currently, guideline and data regarding dose reduction of biologics treatment in axial SpA has not been well established. This randomized controlled trial aims to study the possibility of biologic dose reduction in patients with axial SpA. The primary measure will be the occurrence of disease flare up in participants undergoing biologics tapering compared with participants on standard dose of treatment. The study also aims to evaluate the role of anti-drug antibodies in disease flare, the effect of biologics dose reduction on structural changes, and the cost effectiveness of biologics dose reduction. The results of this study will be crucial for clinical decisions and establishing future guidelines regarding dose reduction of biologics in SpA.

The impact of anti-TNF treatment on Wnt signaling, noggin, and cytokine levels in axial spondyloarthritis.

Anti-tumor necrosis factor (anti-TNF) agents are commonly used in treatment of axial spondyloarthritis (axSpA), but clinical and radiological improvement is not achieved in all patients. We aimed to investigate the impact of anti-TNFs on inflammatory and noninflammatory parameters in patients with axSpA. In this longitudinal study, 30 biologic naïve axSpA patients with high disease activity and 30 healthy controls were enrolled. All patients were treated with anti-TNF agents for 6months. ASDAS-CRP, BASDAI, BASFI, BASMI, patient and physician global assessments were evaluated. C-reactive protein, COX2, TNF-α IL-6, IL-17, IL-22, IL-23, IL-33, sclerostin, dickkopf-1, and noggin levels were evaluated at baseline and at 6months of anti-TNF treatment. At baseline, axSpA patients had significantly higher median (IQR) TNF-α levels, 34.4 (31.4-37.03) vs. 18.1 (12.1-28.4) pg/ml (p < 0.001), and lower DKK1, 446.7 (356.9-529.3) vs. 1088.7 (951.7-1244.4) pg/ml, and sclerostin, 312.4 (140.8-412.7) vs. 412.3 (295.4-512.8) pg/ml, compared to healthy controls (all p < 0.001). The median (IQR) serum levels of IL-17, IL-22, and IL-33 increased significantly after 6months of anti-TNF treatment, from 93.3 (85.1-104.8) to 102.1 (86.6-114.6) pg/ml (p = 0.026), 159.2 (151.9-178.4) to 183.5 (156.3-304.6) pg/ml (p = 0.033), and 127.8 (106.6-186.1) to 147.06 (128.5-213.4) pg/ml (p = 0.016), respectively. Sclerostin and DKK-1 levels increased significantly after anti-TNF treatment from 312.4 (140.8-412.7) to 405.1 (276.3-452.5) pg/ml (p = 0.018) and 446.7 (356.9-529.3) to 881.3 (663.1-972.2) pg/ml (p < 0.001), while there was no significant change in noggin level. Many inflammatory cytokines increase after anti-TNF treatment and noggin is not affected by anti-TNF treatment in AxSpA. Noggin might be a therapeutic target in patients with axSpA. • Anti-TNF therapy is not sufficient for complete blockage of the inflammatory process in axial spondyloarthritis. • The increase in IL-17, IL-22, and IL-33 may decrease the efficiency of anti-TNF therapy. • Noggin might be a therapeutic target as a complementary or alternative approach to anti-TNF therapy in axial spondyloarthritis.

Physical therapy in axial spondyloarthritis: guidelines, evidence and clinical practice

Physical therapy is recommended for the management of axial spondyloarthritis (axSpA) with the focus of promoting physical activity and prescribing exercise within four domains, outlined recently by the European League against Rheumatism (EULAR): aerobic, resistance, flexibility and neuro-motor exercise. There is an increasing evidence base to support physical therapy interventions in axSpA. We present evidence supporting the use of exercise as treatment for patients with axSpA, recent updates among different exercise modalities, and make clear its critical place in the management of this condition. Recent large, multicentre data have shown that high-intensity exercise can improve disease activity and also positively impact cardiovascular risk factors in these patients. Although international treatment guidelines advocate the inclusion of physical activity and exercise for the optimal management of axSpA, specific guidance about the amount of exercise required to produce a beneficial effect is lacking. Exercise must be used in the management of axSpA, and whilst hydrotherapy and flexibility exercises are traditionally the main focus, other applications, such as strength training, may be underutilized domains. Further studies are needed to determine the dose-response relationship between exercise and axSpA patient subsets.

O36 Exploring NICE criteria for continuing biologic therapies in axial spondyloarthritis: what is a suboptimal response?

O36 Exploring NICE criteria for continuing biologic therapies in axial spondyloarthritis: what is a suboptimal response?

Association between concomitant csDMARDs and clinical response to TNF inhibitors in overweight patients with axial spondyloarthritis

BackgroundThe aim of our study was to investigate the influence of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and body mass index (BMI) on circulating drug levels and clinical response to tumour necrosis factor inhibitor (TNFi) therapy in axial spondyloarthritis (axSpA) patients.MethodsProspective observational study during 1 year with 2 cohorts (Madrid and Amsterdam) including 180 axSpA patients treated with standard doses of infliximab or adalimumab. Patients were stratified by BMI, being 78 (43%) normal weight (18.5–24.9 kg/m2) and 102 (57%) overweight/obese (≥ 25.0 kg/m2). After the first year of treatment, TNFi trough levels were measured by capture ELISA. Clinical response to TNFi was defined as ∆BASDAI ≥ 2 and clinical remission as BASDAI < 2 and CRP ≤ 5 mg/L. Logistic regression models were employed to analyse the association between concomitant csDMARDs and BMI with drug levels and clinical response.ResultsSeventy-nine patients (44%) received concomitant csDMARDs. The administration of concomitant csDMARDs (OR 3.82; 95% CI 1.06–13.84) and being normal weight (OR 18.38; 95% CI 2.24–150.63) were independently associated with serum TNFi drug persistence. Additionally, the use of concomitant csDMARDs contributed positively to achieve clinical response (OR 7.86; 95% CI 2.39–25.78) and remission (OR 4.84; 95% CI 1.09–21.36) in overweight/obese patients, but no association was found for normal-weight patients (OR 1.10; 0.33–3.58).ConclusionsThe use of concomitant csDMARDs with TNFi may increase the probability of achieving clinical response in overweight/obese axSpA patients. Further research studies including larger cohorts of patients need to be done to confirm it.

Recommendations by the Spanish Society of Rheumatology on the Use of Biological Therapies in Axial Spondyloarthritis.

Recent data published on biological therapy in axial spondyloarthritis (axSpA) since the last publication of the recommendations of the Spanish Society of Rheumatology (SER) has led to the generation of a review of these recommendations based on the best possible evidence. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with axSpA. Recommendations were drawn up following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Centre for Evidence Based Medicine at Oxford. The level of agreement was established through the Delphi technique. In this review, we did an update of the evaluation of disease activity and treatment objectives. We included the new drugs with approved therapeutic indication for axSpA. We reviewed both the predictive factors of the therapeutic response and progression of radiographic damage. Finally, we drafted some recommendations for the treatment of patients refractory to anti-tumor necrosis factor, as well as for the possible optimization of biological therapy. The document also includes a table of recommendations and a treatment algorithm. We present an update of the SER recommendations for the use of biological therapy in patients with axSpA.

Recommendations by the Spanish Society of Rheumatology on the Use of Biological Therapies in Axial Spondyloarthritis

ObjectiveRecent data published on biological therapy in axial spondyloarthritis (axSpA) since the last publication of the recommendations of the Spanish Society of Rheumatology (SER) has led to the generation of a review of these recommendations based on the best possible evidence. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with axSpA. MethodsRecommendations were drawn up following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Centre for Evidence Based Medicine at Oxford. The level of agreement was established through the Delphi technique. ResultsIn this review, we did an update of the evaluation of disease activity and treatment objectives. We included the new drugs with approved therapeutic indication for axSpA. We reviewed both the predictive factors of the therapeutic response and progression of radiographic damage. Finally, we drafted some recommendations for the treatment of patients refractory to anti-tumour necrosis factor, as well as for the possible optimisation of biological therapy. The document also includes a table of recommendations and a treatment algorithm. ConclusionsWe present an update of the SER recommendations for the use of biological therapy in patients with axSpA.

Physical activity in axial spondyloarthritis-tails from bench to bedside.

Physical therapy and exercise (recreational activity) are the cornerstones of non-pharmacologic therapy in axial spondyloarthritis (AxSpA) [1, 2]. These are components of physical activity, though physical activity is made up of activities beyond these and also include occupational activity. Not all activities in AxSpA appear to derive the same benefit for patients. In fact, it might be that while some activities are extremely beneficial for disease activity, function, and other outcomes, other activities may be harmful for the disease. The following review will examine animal model-based evidence and epidemiologic studies on physical activity in AxSpA.

Elevated Serum Levels of Sclerostin are Associated with High Disease Activity and Functional Impairment in Patients with Axial Spondyloarthritis.

Recent research suggests that biomarkers may be useful in assessing disease activity, structural damage, and response to therapy in axial spondyloarthritis (axSpA). Our study aims at evaluating the relationship between inflammation and bone remodeling markers and variables assessing disease activity and functional disability in patients with axSpA. Serum levels of sclerostin, matrix metalloproteinase-3 (MMP-3), interleukin-17 (IL-17), and IL-23 were measured in 60 patients with axSpA and 20 healthy controls. Disease activity was evaluated using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Functional status was assessed by Bath Ankylosing Spondylitis Function Index (BASFI) and measures of spinal mobility. Sclerostin levels were more elevated in axSpA patients with high disease activity than in those with low disease activity and in controls. They were significantly correlated with BASFI values (r = 0.29, p = 0.03) and measures of spinal mobility, but not with the classical markers of disease activity (BASDAI, ASDAS, CRP, and ESR). Although both MMP-3 and IL-17 levels were elevated in patients with active disease, they were not correlated with markers of disease activity or with functional disability. The levels of sclerostin, MMP-3, IL-17, and IL-23 were similar in axSpA patients and healthy controls. Elevated levels of sclerostin, MMP-3, and IL-17 were observed in axSpA patients with active disease, suggesting their potential role in assessing disease activity. In axSpA patients, sclerostin levels might be equally influenced by inflammation and level of physical activity. Further studies are required to confirm our findings in order to understand their clinical value.

AB0670 Are There any Differences in Baseline Characteristics between Patients Who Relapsed and Patients Who Remained in Remission or Low Disease Activity at One Year after Dosage Reduction of Biological Therapy in Axial Spondyloarthritis?

BackgroundThere are a few evidence on the dosage reduction of biological therapy in patients with axial Spondyloarthritis in clinical remission (1-4) and there are no studies on the factors that...

How Important is Early Therapy in Axial Spondyloarthritis?

There are 2 groups of drugs that have been shown effective in the treatment of patients with axial spondyloarthritis: nonsteroidal anti-inflammatory drugs and tumor necrosis factor α blockers. Conventional disease-modifying drugs and some other biologics have not been shown clinically efficacious in this disease. This overview discusses the available data on whether early treatment strategies in patients with axial spondyloarthritis have an effect on (1) the percentage of patients reaching clinical remission, (2) achieving drug-free remission, and (3) the progress of radiographic progression in the spine as a parameter for structural damage.