Impact of Janus Kinase Inhibition on the Treatment of Axial Spondyloarthropathies.

Many immune cells and effector molecules (e.g. cytokines, Interferons, growth factors) utilize different combinations of Janus kinase (JAK) and signal transducer and activator of transcription (STAT) molecules to transduce signals from the cell surface to the nucleus, where they regulate transcription. This pathway is basically involved in almost all inflammatory diseases and also in the interleukin (IL)-23/IL-17 cascade, which is an essential part of the pathogenesis of spondyloarthropathies (SpA). Upon evidence from in vitro and in vivo experiments indicating disease-modifying effects of JAK inhibition in inflammatory joint disease, numerous inhibitors of the JAK/STAT pathway (= JAKinibs) with different selectivity against the four members of the JAK family [JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2)] were developed. Trials in rheumatoid arthritis were successful with respect to efficacy and safety, and currently, three JAKinibs are approved for the treatment of rheumatoid arthritis in the European Union. Although new treatment options (anti-IL-23, anti-IL-17, and phosphodiesterase 4 inhibitors) have become available for spondyloarthritis and especially psoriatic arthritis (PsA) within the last years, most of them are biologics and do not address all disease manifestations equally. Therefore, multiple trials were initiated to evaluate JAKinibs in PsA and axial spondyloarthritis (axSpA). A trial of Tofacitinib (OPAL) was successful in PsA and has led to the inclusion of JAKinibs into the treatment algorithm. Currently many trials with JAKinibs are ongoing for PsA and axSpA, with one phase III trial of upadacitinib (selective JAK1 inhibitor) showing good therapeutic response in active radiographic axSpA.

Traditional Chinese medicine (TCM) collaborative care for patients with axial spondyloarthritis (AcuSpA): protocol for a pragmatic randomized controlled trial.

BACKGROUND: Axial spondyloarthritis (AxSpA) is a chronic disease which results in fatigue, pain, and reduced quality of life (QoL). Traditional Chinese medicine (TCM), especially acupuncture, has shown promise in managing pain. Although a TCM collaborative model of care (TCMCMC) has been studied in cancer, there are no randomized controlled trials investigating TCM in AxSpA. Therefore, we will conduct a pragmatic trial to determine the clinical effectiveness, safety, and cost-effectiveness of TCMCMC for patients with AxSpA. We define TCMCMC as standard TCM history taking and physical examination, acupuncture, and TCM non-pharmacological advice and communications with rheumatologists in addition to usual rheumatologic care. The purpose of this paper is to describe the rationale for and methodology of this trial. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 160 patients who are diagnosed with AxSpA and have inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs). Simple randomization to usual rheumatologic care or the intervention (TCMCMC) with a 1:1 allocation ratio will be used. Ten 30-min acupuncture sessions will be provided to patients assigned to the TCMCMC arm. All participants will continue to receive usual rheumatologic care. The primary endpoint - spinal pain - will be evaluated at week 6. Secondary endpoints include clinical, quality of life, and economic outcome measures. Patients will be followed up for up to 52 weeks, and adverse events will be documented. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of a TCMCMC for patients with AxSpA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03420404 . Registered on 14 February 2018.

Axial spondyloarthritis in the USA: diagnostic challenges and missed opportunities.

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that primarily affects the sacroiliac joints and spine. Delayed or inadequate treatment may decrease quality of life and lead to poor long-term outcomes, including irreversible loss of spinal function. In this review, we discuss clinical practice related to axSpA within the USA, including prevalence, diagnosis, reasons for delayed/missed diagnosis, and suggestions for making early diagnosis. The US population prevalence of axSpA (0.9-1.4%) is higher than the diagnostic prevalence (0.2-0.7%). Although the estimated diagnostic delay for axSpA is 14 years in the USA, the disease can be identified earlier if appropriately preselected patients are quickly referred to rheumatologists. Only 37% of patients with ankylosing spondylitis in the USA are diagnosed by rheumatologists; the remaining 63% are diagnosed by primary care (26%), chiropractic/physical therapy (7%), orthopedic surgery (4%), pain clinics (4%), acute care (3%), and other settings (19%). To help reduce diagnostic delay, non-rheumatologist-healthcare professionals are urged to refer patients with back pain and ≥ 1 of 3 SpA features (HLA-B27 positivity, current inflammatory back pain, or x-ray/MRI evidence of sacroiliitis) to a rheumatologist. Prevalence and diagnosis rates of axSpA are disparate in the USA due to the lack of awareness and knowledge among non-rheumatologists. Progress has been made in identifying hurdles causing diagnostic delays. Public health initiatives are needed to guide primary care physicians, physical therapists, chiropractors, and other specialists seeing patients with chronic back pain on methods for suspecting or identifying axSpA and early referral to rheumatologists.

The Efficacy of Tai Chi and Yoga in Rheumatoid Arthritis and Spondyloarthropathies: A narrative biomedical review.

Rheumatoid arthritis (RA) and spondyloarthropathies (SpA) are among the most common inflammatory rheumatic diseases, which might induce chronic pain for their sufferers. Mind-body interventions like Tai Chi and yoga are among the many alternative therapies for combatting chronic pain. This review aims to overview the articles about their effectiveness in RA and SpA. We searched PubMed/MEDLINE, Scopus, and Web of Science for English-language sources from their inception through September 2017. Case-control studies, interventional studies, and case series that included more than three cases and randomized crossover studies were included. The literature search retrieved 133 non-duplicate records, and 15 of them were eligible and were included in this review. The influence of Tai Chi remains debatable in RA, while there is only one study that investigated its efficacy in SpA. Yoga seems effective in decreasing pain and inflammation while increasing quality of life. There are no data available about its effect on SpA. Even after a thorough research, the number of articles is quite limited on the effectiveness of Tai Chi and yoga in RA and SpA. While these complementary approaches still show some promise as alternative therapies in RA and SpA, the literature lacks long-term studies with larger patient groups.

Spine Conditions: Mechanical and Inflammatory Low Back Pain.

Mechanical low back pain (LBP) is an injury or derangement of an anatomic structure in the low back. When evaluating patients with LBP, clinicians should maintain clinical suspicion for vertebral fracture, cancer, and cauda equina syndrome. Management includes patient education focused on exercise, massage, and behavioral approaches such as cognitive behavioral therapy. Acupuncture can be an effective alternative and specific herbal supplements may provide short-term pain relief. The prognosis for patients with mechanical LBP is good. Inflammatory LBP is pain resulting from a systemic inflammatory condition, often referred to as axial spondyloarthritis. Ankylosing spondylitis is chronic inflammatory LBP characterized by early onset (mean age 24 years), with a higher prevalence in men. Five clinical parameters can help identify inflammatory LBP: improvement with exercise, pain at night, insidious onset, onset at younger than 40 years, and no improvement with rest. Management of inflammatory LBP typically includes nonsteroidal anti-inflammatory drugs and structured exercise programs, with emphasis on the involvement of a rheumatology subspecialist. Spondyloarthritis is associated with other rheumatic or autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. These should be considered when evaluating patients with inflammatory LBP.

Renal osteodystrophy: neurosurgical considerations and challenges.

BACKGROUND: Dialysis-associated destructive spondyloarthropathy (DSA) is the major bony complication of end-stage renal disease, most commonly found in the lower cervical region. The risk factors for developing dialysis-associated DSA include duration of hemodialysis and patient age. Patients with DSA have a higher incidence of osteoporosis and poor bone mineral density, which may place them at greater risk of atraumatic fractures, instrumentation failure, and neurologic compromise. METHODS: We describe a case of cervical radiculopathy due to dialysis-associated DSA atraumatic vertebral body fractures with a postoperative course that was complicated by instrumentation failure. We reviewed the literature regarding all 138 published cases, presenting the complications, surgical treatment options, and outcomes. RESULTS: A 44-year-old dialysis-dependent man presented with acute neck pain, radiculopathy, and weakness due to atraumatic fracture of C5 and C6 vertebral bodies. He underwent anterior C5 and C6 corpectomies, reconstruction with mesh cage and plate, and supplemental posterior instrumentation (C4-T1). Six weeks later, a computed tomography scan revealed anterior translation across the instrumented area with failure of the posterior instrumentation. He subsequently underwent traction, revision reinstrumentation from C2 to T5, and placement of external halo ring/jacket for 6 months. At 18 months later, he remains ambulatory without evidence of construct failure. CONCLUSIONS: Patients with renal osteodystrophy present a challenge for the spine surgeon due to compromised bone density. Hardware failure at the bone-construct interface is common in these patients, with revision surgery needed in 22% of published cases. Longer constructs with circumferential instrumentation and halo immobilization may minimize the risk of pseudoarthrosis and construct pull-out.

[Spondyloarthropathies--clinical evaluation and physical therapy]. / Fizikalna terapija i klinicka evalucija uspjesnosti lijecenja bolesnika sa spondiloartropatijama.

Spondyloarthropathy is a group of chronic autoimmune disorders including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, acute anterior uveitis and undifferentiated spondyloarthropathies. The spondyloarthropathies share common clinical, radiological, and genetic features that are clearly distinct from other inflammatory rheumatic diseases. The major goal in the management of patients with rheumatic disorders is to control or cure the disease and to preserve and control function and health status. To measure treatments' efficacy standardized assessment of organ morphology, function, and of health status are required. The instruments for measuring health status or quality of life cover a variety of dimensions of health, including physical, social, and emotional functioning. Measurements used to evaluate the efficacy of treatments in ankylosing spondylitis include spinal and chest movement, duration and severity of morning stiffness, and quality of sleep. Health status indices such as the HAQ or AIMS are not readily applicable to spondyloarthropaties. It is reason to use some others: 1. Functional status measure S-HAQ for patients with spondylitis by adding five items to the HAQ, to cover the activities identified as most problematic; 2. Functional index for the assessment of ankylosing spondylitis (Dougados Functional Index - DFI) - it is valid and reliable and shows sufficient responsiveness; S-HAQ appears at least as sensitive to change as the Dougados Index; 3. The Leeds Disability Questionnaire assesses disability in ankylosing spondylitis, inquiring about four areas of function: mobility, bending down, reaching up and neck movements, and postures; 4. The Bath Ankylosing Spondylitis Functional Index (BASFI) 10 item self-administered questionnaire to assess function and activities of daily living in patients with ankylosing spondylitis. Physical therapy is one of the most important way to restore function and health status in patients with spondyloarthropathies, esspecially individual kinesitherapy. We use and many other procedures combine them with kinesitherapy (ultrasound, cryotherapy, electrotherapy, laser ...).

Recent advances in the treatment of the seronegative spondyloarthropathies.

The observation that anti-tumor necrosis factor (anti-TNF) therapies dramatically reduce joint pain and inflammation and retard radiographic progression in rheumatoid arthritis (RA) has created a considerable amount of enthusiasm among rheumatologists and has set new treatment standards for patients with inflammatory joint disease. A central question that has emerged is whether these agents are effective in treating the seronegative spondyloarthropathies (SpA). A related question is whether second-line agents such as methotrexate (MTX) can improve axial inflammation and functional measures if administered early in disease. The SpA are a cluster of inflammatory arthridites encompassing ankylosing spondylitis (AS), psoriatic arthritis (PsA), Reiter's syndrome/reactive arthritis (ReA), and the arthritis associated with inflammatory bowel disease. These disorders share similar clinical and immunogenetic features including axial arthritis and enthesopathy, a general predilection for males and patients positive for the MHC class I alleles, the absence of rheumatoid factor, and association with infections of the intestinal and genitourinary tracts. Reclassification of SpA based on axial or peripheral involvement may be more relevant from a pathophysiologic and therapeutic perspective than the current stratification, given the strong association between axial disease and the HLAB27 allele and the relative resistance of axial disease to conventional anti-inflammatory therapy.