Treatment Of Active Ankylosing Spondylitis Research Articles

Clinical and Economic Benefit of Advanced Therapies for the Treatment of Active Ankylosing Spondylitis.

Recent changes to treatment guidelines for ankylosing spondylitis (AS) have listed first-line advanced therapies as tumor necrosis factor (TNF), interleukin (IL)-17, and Janus kinase (JAK) inhibitors. This study sought to assess the comparative clinical and economic benefit of advanced therapies approved for AS. A systematic literature review was conducted to identify randomized clinical trials for JAK inhibitors (upadacitinib [UPA], tofacitinib [TOF]), anti-IL-17 therapies (secukinumab [SEC], ixekizumab [IXE]), and TNF inhibitors (adalimumab [ADA], etanercept [ETN], golimumab [GOL]) used for the treatment of active AS. Clinical efficacy was evaluated by Assessment of Spondyloarthritis International Society40 (ASAS40) criteria and treatment discontinuation due to adverse events (AEs) was used to generate response rates synthesized via a Bayesian network meta-analysis. Number needed to treat (NNT) was calculated as the reciprocal of incremental response rate of each treatment versus placebo. Cost per ASAS40 responder (CPR) was calculated as the 12-week treatment costs divided by ASAS40 response rates. Data were stratified by biologic treatment status (i.e., biologic naïve [bio-naïve] or inadequate response or intolerance to biologics [bio-IR]) for efficacy and CPR analyses. Among bio-naïve patients, the response rate for ASAS40 was 53.6% for UPA-treated patients, whereas most other treatments had response rates between 41% and 49%. NNTs were lowest for UPA-treated patients at 2.8 (other therapies 3.2-4.8). Estimated CPR among UPA-treated patients was lowest (UPA $39.5k vs others $44.2k-102.5k). Efficacy and CPR trends were similar among bio-IR and TNF-IR patients. Among bio-naïve and bio-IR patients, the rate of AEs leading to discontinuation was lowest among UPA and SEC-treated patients (0.0, others 0.6-3.7%). Relative to other treatments assessed in this study, UPA demonstrated numerically greater clinical and economic benefit for the treatment of AS. Head-to-head or real-world comparisons of these therapies are warranted and may inform clinical decision-making.

Efficacy and safety of Janus kinase inhibitors in patients with ankylosing spondylitis: A systematic review and meta-analysis

ObjectivesTo assess the efficacy and safety of janus kinase (JAK) inhibitors in the treatment of ankylosing spondylitis (AS). MethodsWe searched the PubMed and Cochrane Central Register of Controlled Trials to Nov 1, 2021. We included all randomized controlled trials (RCTs) evaluating JAK inhibitors in the treatment of AS. Two reviewers independently selected studies, extracted data and assessed the risk of bias. ResultsFour RCT studies with 779 participants were included in the meta-analysis. Compared with placebo group, percentages of participants achieving responses of Assessment of spondyloarthritis international society(ASAS) 20, ASAS 40, ASAS 5/6, Bath AS disease activity index (BASDAI) 50 were significantly higher in JAK inhibitor group respectively; changes from baseline in AS disease activity score using C-reactive protein(ASDAS-CRP), Maastricht AS enthesitis score (MASES), AS Quality of Life (ASQoL) score, short-form-36 health survey physical component summary (SF-36 PCS) score, BASDAI, Bath AS functional index (BASFI), Bath AS metrology index (BASMI), Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) score, SPARCC joint score and Work Productivity and Activity Impairment (WPAI) Overall Work Impairment score showed significant improvements in JAK inhibitor group. The incidence of adverse events (AEs) and severe adverse events (SAEs) showed no significant differences between the JAK inhibitor and placebo groups. ConclusionsJAK inhibitors showed a satisfactory and promising efficacy in the treatment of active AS not only in mitigating disease activity, but also substantially improving patient's physical function, emotional well-being and social participation. The results of this meta-analysis provide solid evidence for JAK inhibitor as a novel therapeutic strategy for patients with active AS.

PMS49 - The Cost Effectiveness of Tumour Necrosis Factor-α Inhibitors For Ankylosing Spondylitis And Non-Radiographic Axial Spondyloarthritis

Tumour necrosis factor (TNF)-α inhibitors (anti-TNFs) are used when ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-AxSpA) have not responded to conventional therapy. This research aimed to conduct a systematic review and develop an economic model to determine the clinical and cost-effectiveness of adalimumab, certolizumab pegol, etanercept, golimumab and infliximab, for the treatment of active AS or severe nr-AxSpA. Data from randomised controlled trials (RCTs) were synthesised using Bayesian network meta-analysis. A decision model was developed with a generalised evidence synthesis framework that pooled change in disease activity (BASDAI) and simultaneously synthesised information on function (BASFI) to determine the burden of disease in the economic model. The model had a lifetime horizon and considered costs from an NHS perspective. Health effects were expressed in quality-adjusted life-years. 28 eligible RCTs were identified. In both AS and nr-AxSpA, anti-TNFs produced clinically important benefits in improving function and reducing disease activity. Efficacy estimates were consistently slightly smaller for nr-AxSpA, most noticeably for BASFI and BASDAI 50. Statistical (and clinical) heterogeneity was more apparent in nr-AxSpA, making the reliability of the nr-AxSpA meta-analysis results questionable. In AS, anti-TNFs were approximately equally effective. Importantly, evidence on the effect of anti-TNFs in delaying disease progression was limited; ongoing long-term studies should help inform this. The model, which addressed many of the issues of earlier evaluations, generated incremental cost-effectiveness ratios ranging from £19,240 to £66,529 depending on anti-TNF therapy used and modelling assumptions. In both AS and nr-axSpA, anti-TNFs produce benefits to patients in terms of improving function and reducing disease activity. Anti-TNFs may be an effective use of NHS resources depending on which assumptions are considered appropriate in terms of the patient trajectory following treatment discontinuation, the long-term effect of treatments on function and disease activity and the utility model used.

Network Meta-Analysis and Cost Per Responder of Tumor Necrosis Factor-α and Interleukin Inhibitors in the Treatment of Active Ankylosing Spondylitis.

IntroductionBiologic therapies have improved the clinical management of ankylosing spondylitis (AS). Few head-to-head studies have directly compared the efficacy of these agents. This study was conducted to indirectly compare the efficacy of biologic agents for treatment of active AS.MethodsA targeted literature review was conducted to identify randomized clinical trials for adalimumab, infliximab, golimumab, certolizumab pegol, etanercept, and secukinumab for the treatment of active AS. The clinical efficacy was evaluated using ASAS20 and ASAS40 and synthesized via a Bayesian network meta-analysis. Number needed to treat (NNT) was calculated as the reciprocal of incremental response rate of each biologic versus placebo. Comparisons were also made in terms of cost per incremental ASAS20 or ASAS40 responder.ResultsFifteen studies were identified, which included ASAS20 and/or ASAS40 response rates at Week 12 to Week 16. Patients with AS treated with infliximab had the lowest NNT for ASAS20 of 2.3, followed by those treated with adalimumab (2.8) and etanercept (2.9). Adalimumab had the lowest 12-week cost per additional ASAS20 responder at $26,888, followed by infliximab at $28,175 and golimumab at $28,199. Patients treated with infliximab also had the lowest NNT for ASAS40 (2.6), followed by those treated with adalimumab (2.8) and secukinumab (3.5). Adalimumab had the lowest cost per additional ASAS40 responder at $26,898, followed by infliximab at $32,508 and etanercept at $34,406.ConclusionInfliximab had the lowest NNT to achieve an additional ASAS20/40 response, and adalimumab had the lowest cost per ASAS20/40 responder among biologic agents for the treatment of active AS.FundingAbbVie.

Clinical observation and effect of stains collapse of traditional Chinese medicine in combination with tumor necrosis factor antagonist in treating ankylosing spondylitis

Objective To study the clinical effect, safety of stains collapse of traditional Chinese medicine (TCM) combined with tumor necrosis factor-alpha (TNF-α) antagonist-a recombinant human tumor necrosis factor receptor:Fc fusion protein (rhTNF:Fc) and sulfasalazine (SSZ) in treatment of active ankylosing spondylitis (AS). Methods A total of 98 patients of AS of Gansu Provincial Hospital were divided into two groups in random, the western medicine group (rhTNF:Fc and SSZ, n=46) and the combining group (stains collapse of TCM, rhTNF:Fc and SSZ, n=52). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), Patient Global Assessment (PGA), Visual Analogue Scale (VAS) of night pain, VAS of total pain, time of morning stiffness, TCM symptom score, distance between occipital and wall, distance between finger and ground, thoracic activity, Schober test, and erythrocyte sedimentation rate (ESR), C reactive protein (CRP), adverse reactions before and after treatment were observed and the clinical effect was evaluated in two groups. Results A total of 86 patients achieved the study finally, 45 patients in the combining group and 41 patients in the western medicine group. The effective rate of ASAS20 was better in the combining group than that in the western medicine group(χ2=4.814, P=0.028), the Bath ankylosing spondylitis disease activity index (BASDAI) 50 showed no significant difference between the two group (χ2=0.100, P=0.752). The total effective rate in the combining group than that in the western medicine group(χ2=3.873, P= 0.049). In comparison with the same group before treatment, the above indicators were improved after treatment (P 0.05). The adverse reactions showed no significant difference (P > 0.05). Conclusions Stains collapse of TCM combined with rhTNF:Fc was more effective than single method in treatment of AS, it can alleviated the symptoms, body signs and body function, decrease indexes of inflammation, which has dramatic effect and good safety in clinic. Key words: Spondylitis, ankylosing; Observation; Nursing care; Tumor necrosis factor-α; Stains collapse of traditional Chinese medicine

Psychometric characteristics of the short form 36 health survey and functional assessment of chronic illness Therapy-Fatigue subscale for patients with ankylosing spondylitis.

BackgroundWe evaluated the psychometric characteristics of the Short Form 36 (SF-36) Health Survey and the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale in patients with ankylosing spondylitis (AS).MethodsWe analyzed clinical and patient-reported outcome (PRO) data collected during 12-week, double-blind, placebo-controlled periods of two randomized controlled trials comparing adalimumab and placebo for the treatment of active AS. The Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and other clinical measures were collected during the clinical trial. We evaluated internal consistency/reliability, construct validity, and responsiveness to change for the SF-36 and FACIT-Fatigue.ResultsThe SF-36 (Cronbach alpha, 0.74-0.92) and FACIT-Fatigue (Cronbach alpha, 0.82-0.86) both had good internal consistency/reliability. At baseline, SF-36 and FACIT-Fatigue scores correlated significantly with Ankylosing Spondylitis Quality of Life scores (r = -0.36 to -0.66 and r = -0.70, respectively; all p < 0.0001). SF-36 scores varied by indicators of clinical severity, with greater impairment observed for more severe degrees of clinical activity (all p < 0.0001). FACIT-Fatigue scores correlated significantly with SF-36 scores (r = 0.42 to 0.74; all p < 0.0001) and varied by clinical severity (p < 0.05 to p < 0.0001).ConclusionsThe SF-36 is a reliable, valid, and responsive measure of health-related quality of life and the FACIT-Fatigue is a brief and psychometrically sound measure of the effects of fatigue on patients with AS. These PROs may be useful in evaluating effectiveness of new treatments for AS.Trial RegistrationClinicalTrials.gov: NCT00085644 and NCT00195819

Dramatic efficacy of infliximab in cauda equina syndrome complicating ankylosing spondylitis

Cauda equina syndrome is an uncommon complication of ankylosing spondylitis (AS) characterized by the slow and insidious development of severe neurologic impairment. Imaging studies usually show a wide lumbar canal with dural ectasia. No medical or surgical treatment has been proven effective. We managed the care of a 66-year-old man who had longstanding AS and clinical features of cauda equina syndrome, including anal incontinence and buttock hypoesthesia. Magnetic resonance imaging demonstrated no cause for these symptoms other than AS. The patient was treated with infliximab, a monoclonal antibody to tumor necrosis factor alpha that is used for the treatment of active AS. After 3 infliximab infusions, sphincter control and sensation were normal. The treatment was continued, and he was still doing well 1 year later. This is the first report of an effective treatment for cauda equina syndrome complicating AS. Our case report strongly supports an inflammatory mechanism to this condition.