Treatment Of Axial Spondyloarthritis Research Articles

Targeting the Interleukin-23/Interleukin-17 Inflammatory Pathway: Successes and Failures in the Treatment of Axial Spondyloarthritis.

The IL-23/IL-17 pathway has been implicated in the etiopathogenesis of axial spondyloarthritis through studies of genetic polymorphisms associated with disease, an animal model with over-expression of IL-23 that resembles human disease, and observations that cytokines in this pathway can be found at the site of disease in both humans and animal models. However, the most direct evidence has emerged from clinical trials of agents targeting cytokines in this pathway. Monoclonal antibodies targeting IL-17A have been shown to ameliorate signs and symptoms, as well as MRI inflammation in the spine and sacroiliac joints, in patients with radiographic and non-radiographic axial spondyloarthritis. This was evident in patients refractory to non-steroidal anti-inflammatory agents as well as patients failing treatment with tumor necrosis factor inhibitor therapies. Treatment with a bispecific antibody targeting both IL-17A and IL-17F was also effective in a phase II study. Post-hoc analyses have even suggested a potential disease-modifying effect in reducing development of spinal ankylosis. However, benefits for extra-articular manifestations were limited to psoriasis and did not extend to colitis and uveitis. Conversely, trials of therapies targeting IL-23 did not demonstrate any significant impact on signs, symptoms, and MRI inflammation in axial spondyloarthritis. These developments coincide with recent observations that expression of these cytokines is evident in many different cell types with roles in innate as well as adaptive immunity. Moreover, evidence has emerged for the existence of both IL-23-dependent and IL-23-independent pathways regulating expression of IL-17, potentially associated with different roles in intestinal and axial skeletal inflammation.

Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The present study was undertaken to investigate the effectiveness and safety of dose reduction of tumor necrosis factor inhibitor (TNFi) therapy in the treatment of axial spondyloarthritis (SpA) compared to usual care. We searched the Cochrane Central Register of Controlled Trials, Embase, Medline, and trial registries. We screened, extracted data, and assessed risk of bias in duplicate. Data were pooled using random-effects models; subgroup analyses were performed for type of TNFi, prior TNFi exposure, and follow-up duration. Outcomes of interest were Assessment of SpondyloArthritis international Society (ASAS) response and remission criteria, disease activity, relapse, and safety. We included 6 randomized trials with 747 participants (442 with ankylosing spondylitis and 305 with nonradiographic axial SpA). Compared to the standard dose, there were fewer events with the reduced dose for the ASAS criteria for 40% improvement (risk ratio [RR] 0.62 [95% confidence interval (95% CI) 0.49, 0.78]) and for ASAS partial remission (RR 0.17 [95% CI 0.06, 0.46]). There was a mean increase in the Bath Ankylosing Spondylitis Disease Activity Index score (mean difference [MD] 0.35 [95% CI 0.10, 0.60]) and no difference in C-reactive protein levels (MD 0.16 [95% CI -0.76, 1.07]) with the reduced dose. There were more disease flares/relapses (RR 1.73 [95% CI 1.32, 2.27]) with the reduced dose. There were no differences in infection rates (incidence rate ratio [IRR] 0.98 [95% CI 0.76, 1.25]) or injection/infusion reactions (IRR 0.71 [95% CI 0.42, 1.19]). Patients with axial SpA may experience little to no clinical benefit from reduction of TNFi therapy. Maintaining the standard dose probably improves the sustained effect on disease activity and helps to prevent disease flare.

POS1014 CENTRAL SENSITIZATION HAS MAJOR IMPACT ON QUALITY OF LIFE IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS

Background:Maintaining optimal health-related quality of life (QoL) is the ultimate goal of treatment in axial spondyloarthritis (axSpA). Chronic pain has a large potential impact on QoL. Central sensitization (CS) may explain part of the chronic pain in axSpA. However, the role of central sensitization (CS) herein has only been studied to a limited degree and current axSpA guidelines pay little attention to identification and treatment of CS.Objectives:To explore the relationship between CS and QoL in axSpA.Methods:Consecutive outpatients with axSpA from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included. CS was assessed with the Central Sensitization Inventory (CSI; 0-100), QoL with the AS Quality of Life questionnaire (ASQoL; 0-18) and disease activity with the AS Disease Activity Score (ASDASCRP). A high probability of CS was defined as CSI score ≥40 and active disease as ASDASCRP score ≥2.1. Patient characteristics and clinical assessments were compared between groups with CSI score <40 and ≥40.(1) Multivariable regression analysis was conducted to investigate the relationship between CSI and ASQoL scores, correcting for potential confounders.Results:Of the 178 axSpA patients with available CSI score, 149 completed the ASQoL. Mean age of the 178 included patients was 47.4 ± 14.1 years, 78 (44%) were female, mean symptom duration was 21.4 ± 13.6 years and 88 (52%) were using bDMARDS. Mean CSI score was 38.0 ± 14.1, mean ASQoL 6.0 ± 5.3 and mean ASDASCRP 2.1 ± 1.0. CSI score ≥40 was significantly associated with higher mean ASQoL (9.7 vs. 3.3), higher mean ASDASCRP (2.6 vs. 1.7), female gender (60% vs. 29%) and more often entheseal involvement (61% vs. 26%) (Table 1).Table 1.Selection of patient characteristics, disease activity and clinical outcome variables for patients with axSpA, divided in subgroups for CSI score with a cutoff point of 40.CharacteristicsAll patientsn = 178CSI<40n = 98 (55%)CSI≥40n = 80 (45%)Age (years)47.4 ± 14.148.7 ± 15.045.8 ± 12.7Female78 (44)27 (29)44 (60)*Symptom duration (years)21.4 ± 13.621.5 ± 13.521.2 ± 13.8HLA-B27+133 (79)70 (79)54 (79)Smoker45 (27)28 (32)15 (23)BMI (kg/m2)26.7 ± 5.026.2 ± 4.427.5 ± 5.8Completed higher education181 (71)48 (70)34 (76)Biological use88 (52)49 (52)39 (51)RDCI (0-9)0.0 (0.0 – 1.0)0.0 (0.0 – 1.0)0.0 (0.0 – 1.8)Peripheral arthritis210 (6)5 (6)5 (8)Entheseal involvement364 (40)23 (26)38 (61)*ASDASCRP2.1 ± 1.01.7 ± 0.92.6 ± 1.0*CRP (mg/ml)2.9 (1.1 – 6.8)2.6 (1.1-6.0)3.6 (1.4 – 7.0)ASQoL (0-18)6.0 ± 5.33.3 ± 3.69.7 ± 4.9*CSI (0-100)38.0 ± 14.128.0 (23 – 34)50.0 (43.0 –56.0)N/AValues are n (%), mean ± SD or median (IQR).1International Standard Classification of Education (ISCED) level >4; 2Swollen Joint Count >0; 3Maastricht Ankylosing Spondylitis Enthesitis Score >0. *p<0.001. ASDASCRP: Ankylosing Spondylitis Disease Activity Score; ASQoL: Ankylosing Spondylitis Quality of Life questionnaire; CRP: C-reactive protein; CSI: Central Sensitization Inventory; RDCI: Rheumatic Disease Comorbidity Index.Patients with low ASDASCRP (<2.1) and also low CSI score (<40) showed good QoL (median ASQoL 1.1). Patients with low ASDASCRP combined with high CSI score (≥40) and patients with high ASDASCRP (≥2.1) combined with low CSI score reported worse QoL (median ASQoL 5.6 and 4.1, respectively). Patients with high ASDASCRP and also high CSI score reported the worst QoL (median ASQoL 12.0). (Figure 1).Figure 1.ASQoL score in patients with axSpA with CSI score ≥40 and <40, divided for ASDASCRP (cutoff 2.1)Additionally, in univariable analysis, the CSI score explained a large proportion of the variation of the ASQoL (R2=0.46). This association remained significant after correction for ASDASCRP, gender, symptom duration, entheseal involvement, smoking status, BMI category, educational level and comorbidities in multivariable analysis (CSI p<0.001).Conclusion:In daily clinical practice, CS seems strongly related to patient-reported QoL in patients with long-term axSpA.

Twenty years of clinical trials in axial spondyloarthritis: what can we learn for the future?

We have now about 20 years of experience with the treatment of axial spondyloarthritis with biologics, which raises the question what we can learn from past experience, and which open questions should be addressed in future investigations. Many studies have shown that axSpA patients - both patients in their nonradiological and radiological stage - respond similarly well to biologic treatment and these patients should be seen as having the same disease at different stages. AxSpA respond best to TNF-blocker - and probably also to other biologics - if the disease duration is short and if objective parameters of inflammation, such as C-reactive protein or MRI are positive. Primary aim of treatment is to reach and maintain clinical remission. Once remission is achieved, it can be maintained by continuing treatment, and in a proportion of yet not well defined patients the drug dose can be reduced without inducing a flare. The recent demonstration of a good efficacy, in addition to TNF blockers, also of IL-17 inhibitors and JAK-inhibitors in axSpA patients raises the question how to select the best patients for the best treatment. Radiographic progression can best be stopped by effectively suppressing inflammation, whether different drugs have here a different effect has still to be defined. More sensitive measurements of radiographic progression are urgently needed. Reaching and maintaining clinical remission and preventing structural bony damage is the primary treatment target in patients with axSpA. How to reach this aim best has to be further explored in the future.

Anti-IL-17 Agents in the Treatment of Axial Spondyloarthritis.

Axial spondyloarthritis (axSpA) describes a group of chronic inflammatory rheumatic diseases primarily involving the axial skeleton. IL-17 is involved in the pathogenesis of numerous inflammatory diseases, including inflammatory arthritis. Until a few years ago, the only biological agents licensed for the treatment of axSpA and nr-axSpA were TNF inhibitors. However, as some patients did not respond to TNF inhibition or experienced secondary failure, the introduction of the first two IL-17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) has extended the treatment options, and there are now three others (bimekizumab, brodalumab and netakimab) in various stages of clinical development. The last ten years have seen the development of a number of therapeutic recommendations that aimed at improving the management of axSpA patients. The aim of this narrative review of the published literature concerning the role of IL-17 in the pathogenesis of SpA, and the role of IL-17 inhibitors in the treatment of axSpA, is to provide a comprehensive picture of the clinical efficacy and safety of the drugs themselves, and the treatment strategies recommended in the international guidelines.

The Role of Sacroiliac Joint Steroid Injections in the Treatment of Axial Spondyloarthritis.

Objectives This study aims to investigate the effects of fluoroscopy-guided sacroiliac joint steroid injection in patients with acute bilateral sacroiliitis diagnosed with axial spondyloarthritis (axSpA) and how those injections affect the current need for nonsteroidal anti-inflammatory drug (NSAID) usage.Patients and methods We retrospectively evaluated 43 patients (28 males, 15 females; mean age, 31.7±6.3 years; range, 18 to 44 years) fulfilling the Assessment of SpondyloArthritis international Society 2009 criteria for axSpA between June 2015 and May 2016. One group included 22 patients (injection group) treated with sacroiliac joint steroid injection (triamcinolone acetonide) and the other group included 21 patients (non-injection group) not receiving the injection. All 43 patients in both groups were treated with indomethacin peroral. Pre-treatment, first week and first, third and sixth month follow-up examinations were evaluated.Results A ≥50% reduction in the numeric rating scale score compared with the baseline was considered as significant pain relief. The mean pain relief rates in patients receiving injections were higher at all inspections. This difference was statistically significant at first week (p<0.05). When groups were compared, no difference was found in the Bath Ankylosing Spondylitis Disease Activity Index scores (p>0.05). There was no statistically significant difference between the two groups when indomethacin dose was evaluated cumulatively for six months (p>0.05).ConclusionFluoroscopy-guided sacroiliac joint steroid injections can be recommended in patients with active sacroiliitis, particularly in those with severe axial pain, for rapid analgesia in the initial term. It was concluded that steroid injections applied to the sacroiliac joint did not affect disease activity. It is noteworthy that there is a trend to reduce the use of NSAIDs in patients receiving these injections, although it does not make a statistically significant difference in the long term.

IL-23/IL-17炎症通路在中轴型脊柱关节炎发病机制及治疗中的研究进展

IL-23/IL-17炎症通路在中轴型脊柱关节炎发病机制及治疗中的研究进展

High-Intensity Exercise Improves Fatigue, Sleep, and Mood in Patients With Axial Spondyloarthritis: Secondary Analysis of a Randomized Controlled Trial.

ObjectiveAlthough exercise is recommended in the treatment of axial spondyloarthritis (axSpa), the focus has been on flexibility, and the effect of high-intensity exercises is unknown. The purpose of this study was to investigate the effect of high-intensity exercises on fatigue, sleep, and mood in patients with axSpA.MethodsIn this secondary analysis of a randomized controlled trial, participants were recruited from outpatient clinics at 4 hospitals in Scandinavia. A total of 100 patients with axSpA were randomized to either an exercise group (n = 50) or a control group (n = 50). High-intensity exercise was provided 3 times per week for 3 months and supervised by a physical therapist. The controls received no intervention. Measurements were self-reported at baseline, 3 months, and 12 months: fatigue, using the Fatigue Severity Scale (range = 0–7, 7 = worst, ≥5 = severe); vitality, using the RAND 36-item short-form health survey (SF-36, range = 0–100, 100 = best); sleep, using the Pittsburgh Sleep Quality Index (range = 0–21, 21 = worst, >5 = poor quality); mood, using the General Health Questionnaire 12 (range = 0–36, 36 = worst); and general health, using the EUROQoL (range = 0–100, 100 = best).ResultsA total of 38 participants (76%) in the exercise group followed ≥80% of the exercise protocol. At 3 months, there was a significant beneficial effect on fatigue (mean group differences = −0.4, 95% CI = −0.7 to −0.1), vitality (5.0, 95% CI = 1.1 to 10.5), mood (−2, 95% CI = −3.7 to −0.04), and general health (9.0, 95% CI = 3.3 to 14.7) but no effect on sleep (−1.1, 95% CI = −2.1 to 0.2). Compared with the control group, the exercise group had a reduced rate of severe fatigue and poor sleep. No differences were seen between the groups at 12 months.ConclusionsA 3-month exercise program had a beneficial effect on fatigue, sleep, mood, and general health in patients with axSpA at the end of the intervention; however, no long-term effects were seen.ImpactHigh-intensity cardiorespiratory and strength exercises should be considered as important in exercise programs for patients with axSpA.

Novel whole-body magnetic resonance imaging response and remission criteria document diminished inflammation during golimumab treatment in axial spondyloarthritis.

To investigate criteria for treatment response and remission in patients with axial SpA as assessed by whole-body magnetic resonance imaging (WB-MRI) of axial and peripheral joints and entheses during treatment with golimumab. We performed an investigator-initiated cohort study of 53 patients who underwent WB-MRI at weeks 0, 4, 16 and 52 after initiation of golimumab. Images were assessed according to the Spondyloarthritis Research Consortium of Canada MRI SI joint inflammation index, Canada-Denmark MRI spine inflammation score and the MRI peripheral joints and entheses inflammation index. At weeks 4, 16 and 52, WB-MRI demonstrated an at least 50% reduction of MRI inflammation of the sacroiliac joints in 16, 29 and 32 (30%, 55% and 60%) patients, of the spine in 20, 30 and 31 (38%, 57% and 58%) patients and of peripheral joints and entheses in 8, 17 and 15 (15%, 32% and 28%) patients, respectively. The BASDAI50 response was achieved by 29, 31 and 31 (55%, 58% and 58%) patients, while ASDAS clinically important improvement (ASDAS-CII) was achieved by 37, 40 and 34 (70%, 75% and 64%) patients. WB-MRI remission criteria for spine, sacroiliac joints and peripheral joints and entheses were explored; total WB-MRI remission was attained by 2, 6 and 3 (4%, 11% and 6%) patients. At week 16, among 35 patients with an at least 50% reduction in the MRI Axial Inflammation Index (sacroiliac joint and spine inflammation), 29 (83%) achieved BASDAI50 and 35 (100%) achieved ASDAS-CII; among 16 patients with MRI axial inflammation non-response, 14 (88%) were BASDAI50 non-responders and 11 (69%) did not achieve ASDAS-CII. WB-MRI demonstrated a significant reduction of inflammation in both the spine, sacroiliac joints and peripheral joints and entheses during golimumab treatment. Few patients achieved total WB-MRI remission. Combining spinal and sacroiliac joint inflammation in an MRI Axial Inflammation Index increased the ability to capture response. ClinicalTrials.gov, http://clinicaltrials.gov, NCT02011386.

RABBIT-SpA: anew disease register for axial spondyloarthritis and psoriatic arthritis

The treatment of axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) has changed enormously in recent years due to market authorization of anumber of new biologicals with different modes of action and the increasing use of biosimilars. Real-world data on long-term safety and efficacy under routine daily conditions is not yet sufficient. Therefore, the German Rheumatism Research Center has initiated anew cohort study covering axSpA and PsA. Presentation of initial results from the new register RABBIT-SpA, which was started in May 2017. This is a prospective longitudinal cohort study with asimilar study design to the German biologics register RABBIT. Patients can be included at the start of anew treatment either in the so-called index drug group or in the comparison group (conventional systemic treatment, including non-steroidal anti-inflammatory drugs, NSAID). Follow-up per patient should be at least 5years and preferably 10years. The RABBIT-SpA uses aweb-based documentation system. Up to mid-December 2018 a total of 514 axSpA patients had been documented in RABBIT-SpA, 410 with an index drug and 104 with conventional treatment. There are differences between these treatment groups, e. g. in the duration of the disease and in parameters of disease activity. It is also noticeable that in axSpA patients, approximately 5years lie between the onset of the symptoms and confirmation of the diagnosis. Of the 355 PsA patients, 265 were included with an index drug and 90 with conventional treatment. Of the PsA patients 86% have adominant peripheral manifestation. The average number of pressure tender joints is8 and the average number of swollen joints is4. The online register RABBIT-SpA is well-received by the participating rheumatological institutions. The electronic recording of patient data can be carried out in areasonable time. Participation in the RABBIT-SpA is open to new rheumatological institutions at any time.

Profiling Response to Tumor Necrosis Factor Inhibitor Treatment in Axial Spondyloarthritis.

Lack of response to tumor necrosis factor inhibitor (TNFi) agents is not uncommon, encountered during the treatment of axial spondyloarthritis (SpA) patients, and it can be classified as primary lack of response (PLR) or secondary lack of response (SLR). The primary aim of this study was to evaluate factors associated with TNFi failure types and their characteristics in axial SpA. Adult axial SpA patients who were TNFi naive at the time of baseline evaluation and started receiving their first biologics for active axial disease were identified. Based on the clinical response to the first TNFi, patients were then stratified into 3 groups: PLR, SLR, and responders. Clinical, demographic, and laboratory data were collected and analyzed. There was a total of 249 axial SpA patients in the study (70.7% male, mean ± SD age 37.3 ± 12.4 years), which included PLR (n = 62), SLR (n = 93), and responders (n = 94). PLR patients tended to be older, with a lower HLA-B27 rate, a higher percentage of nonresponder axial SpA patients, and a higher baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score compared to SLR patients or responders. In multiple regression analysis, increasing age, negative HLA-B27, higher baseline BASDAI, and treatment with the soluble TNF receptor protein were the independent predictors of PLR. PLR accounted for nearly 40% of the TNFi failures in axial SpA patients. Older age, negative HLA-B27, higher baseline disease activity, and treatment with soluble TNF receptors were the independent predictors of the primary nonresponse to TNFi.

Emerging treatment options for spondyloarthritis.

The management of spondyloarthritis (SpA) has substantially changed as a consequence of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). However, the treatment options in patients with axial SpA (axSpA) not responding to nonsteroidal anti-inflammatory drugs (NSAIDs) had been restricted to tumor necrosis factor alpha (TNFα) inhibitors for almost 15 years. With the approval of secukinumab, an interleukin (IL)-17A inhibitor, there is a new alternative in the treatment of axial SpA. In patients with psoriatic arthritis (PsA) not responding to conventional therapy with NSAIDs and conventional synthetic DMARDs, therapeutic options are more diverse. In addition to TNFα inhibitors and secukinumab, another IL-17A inhibitor ixekizumab, IL-12/23 blocker ustekinumab, phosphodiesterase-4 inhibitor apremilast, T-cell-mediated pathway inhibitor abatacept, and Janus kinase (JAK) inhibitor tofacitinib are the approved treatment. Nevertheless, there is still an unmet need for further treatment options in both axSpA and PsA. Further therapeutics, such as the dual IL-17A and F inhibitor bimekizumab, IL-17 receptor blocker brodalumab, and JAK inhibitors baricitinib, filgotinib and upadacitinib are in development for these indications. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab are further emerging drugs for PsA. Thus, the number of treatment options in SpA is likely to be increased over the next few years that make identification of optimal treatment strategies essential.

Ankylosing spondylitis and axial spondyloarthritis: recent insights and impact of new classification criteria.

Development of the Assessment in Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis (SpA) was one of the major breakthroughs in the field over the past decade. Despite some concerns related to the specificity of the criteria, they stimulated research into the early stage of the disease. This resulted in major advances in the understanding of the course of the disease, revealing predictors of progression, improvement in early diagnosis and treatment in axial SpA. In this review, we summarize the recent developments resulting from the introduction of the ASAS classification criteria for axial SpA and the implications for research and clinical practice.

Spotlight on certolizumab pegol in the treatment of axial spondyloarthritis: efficacy, safety and place in therapy.

Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of ankylosing spondylitis (AS) in the USA and for AS and non-radiographic axial spondyloarthritis (nr-axSpA) in Europe and in some Latin American countries. CZP lacks Fc region, preventing complement fixation and cytotoxicity mediated by antibody; CZP does not actively cross the placenta, unlike other TNFi. RAPID-axSpA study is a Phase III trial conducted in patients with AS and nr-axSpA as double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Of a total of 325 patients recruited, 107 patients were assigned to placebo and 218 patients to CZP (111 to CZP 200 mg Q2W, 107 to CZP 400 mg Q4W). Improvements in axial involvement, joint involvement, enthesitis and quality of life were reported in patients treated with CZP. Safety profile was like that reported for other TNFi in axSpA patients. In this article, we summarized the pharmacology and we reviewed the efficacy and tolerability of this drug for the treatment of axSpA. Some special considerations of CZP during pregnancy are included. CZP, the latest TNFi to be approved, showed efficacy in all manifestations of AS and nr-axSpA.

Improvements in workplace and household productivity with certolizumab pegol treatment in axial spondyloarthritis: results to week 96 of a phase III study

ObjectivesTo evaluate the effect of certolizumab pegol (CZP) on work and household productivity, and on participation in family, social and leisure activities in patients with axial spondyloarthritis (axSpA), including ankylosing...

188 Real-world data on the use of certolizumab pegol for the treatment of axial spondyloarthritis in clinical practice in Europe: 24-week interim results from a prospective non-interventional cohort study

188 Real-world data on the use of certolizumab pegol for the treatment of axial spondyloarthritis in clinical practice in Europe: 24-week interim results from a prospective non-interventional cohort study

New advances in the understanding and treatment of axial spondyloarthritis: from chance to choice.

Axial spondyloarthritis (axSpA) is a chronic inflammatory condition that encompasses ankylosing spondylitis (AS) as well as non-radiographic axial disease (nr-axSpA) and can lead to chronic pain, structural damage and disability. The introduction of tumour necrosis factor inhibitor (TNFi) drugs for AS heralded a new era of drug therapeutics for what was previously a largely untreatable disease. This has now been expanded with the licensing of secukinumab, an interleukin 17A (IL-17A) inhibitor for the treatment of AS. Although biologic disease modifying antirheumatic drugs (bDMARDs) are not a first line treatment option in AS or axSpA, they are highly effective following incomplete or no response to physiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs). Current research strategies aim to test whether the desired treatment goal of disease remission may now be achievable with early and stratified use of bDMARDs in both AS and nr-axSpA. This review summarizes the current literature on axSpA including pathophysiology, treatment indications, radiographic progression and the evidence for new developments in the treatment of both AS and nr-axSpA.

Disease activity in axial spondyloarthritis after discontinuation of TNF inhibitors therapy.

ObjectiveUse of tumour necrosis factor inhibitors (TNFi) has proved to be an important step forward in the treatment of axial spondyloarthritis (axSpA), but the duration of the therapy as well as the management in case of low disease activity (LDA) or remission are not clearly established. Currently, the identification of potential predictors associated with the treatment discontinuation is the basic purpose of many clinical studies. The aim of this study was to analyze the influence of the discontinuation of TNFi therapy on the disease activity in patients with low disease activity.Material and methodsThe study included 65 patients; 47 of patients (72%) were treated with etanercept, 16 (2%) with adalimumab and 2 (3%) with infliximab.ResultsThe mean age of the patients was 45 years, the mean BASDAI score was 6.8 and VAS for low back pain was 76 mm at baseline. 54 patients with axSpA (83%) achieved LDA after 9 months of anti-TNF therapy. During follow-up 40 patients (74% of patients with LDA) had an increase of the disease activity after mean 14 weeks and needed to restart the treatment with TNFi. After restart of the therapy LDA was regained in all patients after mean 7 weeks. 11 patients (17%) have never achieved LDA and 14 patients (22%) had LDA longer than 6 months without relapse. At baseline higher levels of CRP and ESR were observed in patients with relapse of the disease at the end of treatment and with LDA shorter than 6 months.ConclusionsChanges in the values of disease activity indicators (CRP, ESR) correlated with more stable response to TNFi therapy. Over 50% of patients who were treated with TNFi needed to restart the therapy. Treatment resumption allowed to regain a good clinical effect among affected patients.

Switching tumor necrosis factor inhibitors in the treatment of axial spondyloarthritis.

To assess the impact of switching tumor necrosis factor (TNF)-alpha inhibitors on patients with axial spondyloarthritis (axSpA). PubMed literature searches were conducted using combinations of search terms including ankylosing spondylitis, spondyloarthropathy, spondyloarthritis, switch/switching, drug survival, and TNF/tumor necrosis factor to identify published articles with data on outcomes related to switching biologic therapies in patients with axSpA. Of the 134 studies screened, 21 were identified as reporting data on switching TNF inhibitors in patients carrying a diagnosis of axSpA or ankylosing spondylitis. The most common reasons for switching from the first TNF inhibitor were lack of efficacy (14-68%), loss of efficacy (13-61%), and adverse events/poor tolerability (13-57%). Switching TNF inhibitors was beneficial for a substantial proportion of patients with axSpA who failed to respond to initial or even second TNF inhibitor therapy and adverse effects were not enhanced. Drug survival rates were generally lower for the second (47-72% at 2 years) or third TNF inhibitor (49% at 2 years) than for the first TNF inhibitor (58-75% at 2 years). Predictors of responses in TNF-naïve patients included HLA-B27 positivity, absence of enthesitis, age ≤40 years, elevated C-reactive protein level, good functional status, and shorter disease duration. Predictors of drug survival included male sex and peripheral arthritis. Common characteristics of patients who switched TNF inhibitors included female sex, older age, more severe disease, greater symptom burden, higher erythrocyte sedimentation rate, complete ankyloses, and enthesitis. When the first or even the second TNF inhibitor fails, switching to an alternate one is not an unreasonable clinical therapeutic decision.

Golimumab for the treatment of axial spondyloarthritis

ABSTRACTIntroduction: Anti-TNF drugs have represented an epochal revolution in the treatment of rheumatoid arthritis and spondyloarthritis. In the field of axial spondyloarthritis, golimumab, a fully human monoclonal anti-TNFα administered subcutaneously every 4 weeks, has shown significant efficacy and good safety in patients with ankylosing spondylitis. More recently, it was also indicated as an effective treatment for patients suffering from non-radiographic axial spondyloarthitits.Areas covered: A systematic literature search was completed, using the largest electronic databases (Medline, Embase and Cochrane), with the aim to review all data concerning the administration of golimumab in patients suffering from axial spondyloartritis.Expert opinion: In the 16-week GO-AHEAD study, golimumab was effective in patients with non-radiographic spondyloarthritis with high levels of CRP and/or positive MRI findings, but not in subjects with both negative CRP and MRI. This finding allows for the addressing the of anti-TNF treatment more specifically. Preliminary data concerning an open-label extension of the GO-AHEAD study outlined the high retention-rate of the drug at 52 weeks. The production of antibodies against golimumab is rare and it seems to exert scarce influence on the drug performances. In conclusion, golimumab appears as a very useful and well tolerated anti-TNF agent.