Diagnosis and management of axial spondyloarthritis (axSpA) has vastly improved over the past two decades. With advances in the discernment of immunopathogenesis of this disease, new therapies have ...become available, which are associated with substantial improvement in symptoms, signs and quality of life. The four broad categories of approved treatment options are physical therapy and exercise (which have been known to be beneficial for millennia), NSAIDs (since the 1950s), TNF inhibitors (first FDA approval in 2003) and IL-17 inhibitors (first FDA approval in 2016). In addition, there have been a host of new developments in the axSpA field, including new treatment guidelines, the FDA approval of three biologic DMARDs to treat non-radiographic axSpA, the FDA and EMA approval of Janus kinase (JAK) inhibitors for ankylosing spondylitis, new data on the effect of biologic DMARDs on structural progression in ankylosing spondylitis, strategy trials on tapering or stopping TNF inhibitors in patients in remission, trials of treat-to-target strategy in axSpA, and several new molecules in phase III studies. This Review explores the developments in the management of axSpA.
Majority of patients with axial spondyloarthritis (axSpA) report use of complementary and alternative medicine (CAM) therapies before and even after the diagnosis, due to perceived efficacy and ...wide-spread belief that these modalities lack side effects. In this review, we describe the available scientific evidence for the CAM therapies in axSpA.
Clinical trials of the CAM therapies in axSpA are generally hampered by small sample size, short duration, difficulties in blinding, lack of control groups and strong placebo effect. Nonetheless, exercise programs like Pilates and mind-body techniques such as Tai Chi may have favorable effect on the disease activity and function. Although not yet confirmed, the modulation of the microbiome with the help of probiotics or fecal transplant has face validity given the evolving scientific rationale. Diet has only limited role in the management of axSpA. Deep tissue massage, omega-3 fatty acids and Stanger bath were found to be useful in small studies. CAM therapies are not always entirely well tolerated, particularly the manipulative techniques like chiropractic and Tui-na in patients with advanced disease and osteoporosis. There are no trials of yoga in axSpA despite the wider acceptance and use of yoga as an effective mind-body technique.
Larger and better quality clinical trials of CAM therapies are needed to confirm their efficacy and safety in the management of axSpA and to include them in the 'mainstream' medicine.
Early differentiation between different types of inflammatory arthritis and subsequent initiation of modern treatments can improve patient outcomes by reducing disease activity and preventing joint ...damage. Routine clinical evaluation, laboratory testing, and radiographs are typically sufficient for differentiating between inflammatory and predominantly degenerative arthritis (e.g., osteoarthritis). However, in some patients with inflammatory arthritis, these techniques fail to accurately identify the type of early-stage disease. Further evaluation by ultrasound imaging can delineate the inflammatory arthritis phenotype present. Ultrasound is a noninvasive, cost-effective method that enables the evaluation of several joints at the same time, including functional assessments. Further, ultrasound can visualize pathophysiological changes such as synovitis, tenosynovitis, enthesitis, bone erosions, and crystal deposits at a subclinical level, which makes it an effective technique to identify and differentiate most common types of inflammatory arthritis. Limitations associated with ultrasound imaging should be considered for its use in the differentiation and diagnosis of inflammatory arthritides.
Secukinumab is an anti-interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in ...patients with active ankylosing spondylitis.
In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16.
In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn's disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.
Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.).
Abstract Objective To assess the impact of switching tumor necrosis factor (TNF)-alpha inhibitors on patients with axial spondyloarthritis (axSpA). Methods 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. Results 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% to 68%), loss of efficacy (13% to 61%), and adverse events/poor tolerability (13% to 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% to 72% at 2 years) or third TNF inhibitor (49% at 2 years) than for the first TNF inhibitor (58% to 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. Conclusion When the first or even the second TNF inhibitor fails, switching to an alternate one is not an unreasonable clinical therapeutic decision.
Optimal treatment of nonradiographic axial spondyloarthritis depends on accurate and timely diagnosis of the underlying disease; however, patients present with common symptoms that, in the absence of ...radiographic changes, may confound diagnosis.
In this narrative review, a PubMed literature search was conducted through January 2021, with no date limits, to identify English-language publications discussing classification of nonradiographic axial spondyloarthritis, with an emphasis on clinical features and presentation, differential diagnoses, and mimics of disease. This review describes the epidemiology, clinical features, and burden of disease of nonradiographic axial spondyloarthritis as it relates to the overall axial spondyloarthritis spectrum and discusses mimics and differential diagnoses of nonradiographic axial spondyloarthritis that should be considered when evaluating patients with suspected nonradiographic axial spondyloarthritis in clinical practice.
Recognition of clinical features of nonradiographic axial spondyloarthritis, along with an understanding of comorbid conditions such as fibromyalgia, allows for differentiation from its mimics. Appropriate diagnosis of nonradiographic axial spondyloarthritis is important for aggressive management of disease to reduce pain, avoid loss of function, and improve quality of life.
Objective
To update evidence‐based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).
Methods
We conducted updated ...systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat‐to‐target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel.
Results
Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co‐administration of low‐dose methotrexate with TNFi is not recommended, nor is a strict treat‐to‐target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended.
Conclusion
These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.
The Assessment of Spondyloarthritis International Society (ASAS) axial spondyloarthritis (axSpA) classification criteria marked a major step forward in SpA research, distinguishing axial from ...peripheral disease, and allowing earlier identification through MRI. This facilitated all aspects of research including epidemiology, therapeutics and patient outcomes.
The ASAS axSpA classification criteria have been applied broadly in research, and were validated in a recent meta-analysis of international studies. Concerns arose because of clinical differences between the clinical and imaging arms, which imply different risk for radiographic progression, and perform differently in validation studies. Low specificity of the MRI finding of sacroiliac joint bone marrow edema may lead to misclassification in populations with low axSpA prevalence. We suggest methodology to improve upon the criteria, including rigorous assessment of potential candidate criteria sets, discrete choice experiments to allow consideration of feature weights, and validation. Separately, assessment of structural and inflammatory MRI abnormalities should be performed to refine the MRI definition of sacroiliitis.
The debate regarding the validation and modification of the ASAS axSpA classification criteria should lead to international efforts to build upon the gains made by these criteria, to further refine the axSpA population definitions for research and ultimately improve patient outcomes.
Here, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing ...spondylitis (AS), in a pooled analysis of 21 clinical trials.
Data from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication. Crohn's disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) events were analysed using exposure-adjusted incidence rates (patient incidence rates per 100 patient-years (PY)).
A total of 7355 patients with a cumulative exposure of 16 226.9 PY were included in the pooled analysis. Among 5181 patients with PsO, there were 14 cases of UC, 5 cases of CD and 1 case of IBDU, with exposure adjusted incidence rates (EAIRs) of 0.13, 0.05 and 0.01, respectively. Of these 20 cases, 14 were new-onset. In 1380 patients with PsA, there were 3 cases of UC, 3 cases of CD and 2 cases of IBDU (EAIRs 0.08, 0.08 and 0.05); 7 of these represented new-onset cases. Among 794 patients with AS, there were 4 cases of UC, 8 cases of CD and 1 case of IBDU (EAIRs 0.2, 0.4 and 0.1); 9 were new-onset cases. In the per year analysis, the EAIRs for each indication did not increase over time with secukinumab treatment.
In this pooled secukinumab safety analysis of 7355 patients across 21 clinical trials, cases of IBD events (including CD, UC and IBDU) were uncommon.
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