American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015: recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.(AU)

Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). Treatment with TNFalpha inhibitors reduces disease activity and improves outcomes for patients with RA. This study evaluated the efficacy and safety of certolizumab pegol 400 mg, a novel, poly-(ethylene glycol) (PEG)ylated, Fc-free TNFalpha inhibitor, as monotherapy in patients with active RA. METHODS: In this 24-week, multicentre, randomised, double-blind, placebo-controlled study, 220 patients previously failing > or =1 disease-modifying antirheumatic drug (DMARD) were randomised 1:1 to receive subcutaneous certolizumab pegol 400 mg (n = 111) or placebo (n = 109) every 4 weeks. The primary endpoint was 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 24. Secondary endpoints included ACR50/70 response, ACR component scores, 28-joint Disease Activity Score Erythrocyte Sedimentation Rate 3 (DAS28(ESR)3), patient-reported outcomes (including physical function, health-related quality of life (HRQoL), pain and fatigue) and safety. RESULTS: At week 24, the ACR20 response rates were 45.5% for certolizumab pegol 400 mg every 4 weeks vs 9.3% for placebo (p<0.001). Differences for certolizumab pegol vs placebo in the ACR20 response were statistically significant as early as week 1 through to week 24 (p<0.001). Significant improvements in ACR50, ACR components, DAS28(ESR)3 and all patient-reported outcomes were also observed early with certolizumab pegol and were sustained throughout the study. Most adverse events were mild or moderate and no deaths or cases of tuberculosis were reported. CONCLUSIONS: Treatment with certolizumab pegol 400 mg monotherapy every 4 weeks effectively reduced the signs and symptoms of active RA in patients previously failing > or =1 DMARD compared with placebo, and demonstrated an acceptable safety profile. TRIAL REGISTRATION NUMBER: NCT00548834.

The value of magnetic resonance imaging of the lumbar spine to predict low-back pain in asymptomatic subjects : a seven-year follow-up study.

BACKGROUND: In 1989, a group of sixty-seven asymptomatic individuals with no history of back pain underwent magnetic resonance imaging of the lumbar spine. Twenty-one subjects (31%) had an identifiable abnormality of a disc or of the spinal canal. In the current study, we investigated whether the findings on the scans of the lumbar spine that had been made in 1989 predicted the development of low-back pain in these asymptomatic subjects. METHODS: A questionnaire concerning the development and duration of low-back pain over a seven-year period was sent to the sixty-seven asymptomatic individuals from the 1989 study. A total of fifty subjects completed and returned the questionnaire. A repeat magnetic resonance scan was made for thirty-one of these subjects. Two neuroradiologists and one orthopaedic spine surgeon interpreted the original and repeat scans in a blinded fashion, independent of clinical information. At each disc level, any radiographic abnormality, including bulging or degeneration of the disc, was identified. Radiographic progression was defined as increasing severity of an abnormality at a specific disc level or the involvement of additional levels. RESULTS: Of the fifty subjects who returned the questionnaire, twenty-nine (58%) had no back pain. Low-back pain developed in twenty-one subjects during the seven-year study period. The 1989 scans of these subjects demonstrated normal findings in twelve, a herniated disc in five, stenosis in three, and moderate disc degeneration in one. Eight individuals had radiating leg pain; four of them had had normal findings on the original scans, two had had spinal stenosis, one had had a disc protrusion, and one had had a disc extrusion. In general, repeat magnetic resonance imaging scans revealed a greater frequency of disc herniation, bulging, degeneration, and spinal stenosis than did the original scans. CONCLUSIONS: The findings on magnetic resonance scans were not predictive of the development or duration of low-back pain. Individuals with the longest duration of low-back pain did not have the greatest degree of anatomical abnormality on the original, 1989 scans. Clinical correlation is essential to determine the importance of abnormalities on magnetic resonance images.

Celecoxib versus diclofenac in the management of osteoarthritis of the knee.

OBJECTIVE: A clinical trial was conducted in 600 patients with OA of the knee to test the hypothesis that the specific COX-2 inhibitor, celecoxib, has equivalent efficacy and a superior tolerability/safety profile when compared to diclofenac, the current worldwide standard of care. METHODS: Patients were administered celecoxib 100 mg BID, diclofenac 50 mg TID or placebo for 6 weeks in a multicentre, double-blind. placebo-controlled trial. RESULTS: Primary efficacy measures (index joint pain by VAS, WOMAC index) indicated statistically significant improvement versus placebo for both celecoxib and diclofenac and no statistically significant differences between celecoxib and diclofenac. American Pain Society (APS) measures to assess the rapidity of onset of action showed statistically significant and comparable pain relief versus placebo within 24 h for both celecoxib and diclofenac. More diclofenac patients reported GI side effects than patients treated with either placebo or celecoxib. Diclofenac-treated patients experienced statistically significant elevations in mean hepatic transaminases and serum creatinine and reductions in haemoglobin concentration when compared to placebo, events not observed with celecoxib. CONCLUSION: Celecoxib 200 mg daily is as effective as diclofenac 150 mg daily for relieving signs and symptoms of OA of the knee, including pain, and has a rapid onset of action. However, celecoxib appears to have a superior safety and tolerability profile.

Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.

Low back pain affects a minority of individuals over 65 years of age. Four years after the onset of sciatica, the number of individuals working is independent of their workers' compensation status. A complex interaction of metalloproteinases, cytokines, chondrocytes, and macrophages are necessary for the resorption of herniated intervertebral discs. Positional magnetic resonance imaging in the seated extended posture identifies foraminal narrowing that is not visualized with conventional magnetic resonance studies. Compression associated with cauda equina syndrome must be reversed within 48 hours to preserve neurologic function. The gene for transforming growth factor can be transferred to intervertebral discs, resulting in increased proteogylcan production in a rabbit animal model. An aerobic exercise program is as effective as more expensive exercise programs in the treatment of chronic low back pain. Complementary therapies, willow bark and magnets, have marginal benefit for low back pain. Surgical intervention results in improved function for spinal stenosis patients.

Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.

Low back pain is a common medical problem but has decreased in frequency in the occupational setting over the past decade. The weather affects low back pain but to a minor degree. Physical factors, as well as job satisfaction, play a role in the development and perpetuation of low back pain. In contradistinction to previous measurements, intradiscal pressure has been determined in vivo to be greater in the standing than the sitting position. Adenovirus-mediated gene transfer to nucleus pulposus cells may be the initial stage of a new form of therapy for degenerative disc disease. Bed rest is not more helpful than activity as tolerated for the treatment of sciatica. The outcome of spinal stenosis surgery is more closely associated with the patient's perception of improvement than with the degree of canal narrowing.

Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.

Low back pain continues to affect a significant proportion of the younger, working population between 35 and 45 years of age. An important study has correlated macroscopic and microscopic intervertebral disc alterations starting in the second decade of life with oxidative stress manifested by the presence of N-(carboxylmethyl)lysine. Job satisfaction remains a strong predictive factor for the identification of individuals with acute back pain who will develop chronic pain. Patients with pyogenic vertebral osteomyelitis may have an increase in their erythrocyte sedimentation rate during the first 2 weeks of antibiotic therapy without requiring surgical intervention. Magnetic resonance imaging enhancement of migrated disc fragments identifies individuals who are likely to resolve sciatica without surgical intervention. As many as 25% of individuals with low back pain are symptomatic at 12 months, in contradistinction to the dictum of resolution of pain in 2 months. Nonsteroidal anti-inflammatory drugs and muscle relaxants are a very effective combination for the effective treatment of acute low back pain. A majority of chiropractic manipulations are performed for inappropriate indications.

Management of neck pain: a primary care approach.

Among the many disorders that cause neck pain, biomechanical stress is the most common. Nonoperative therapies offer relief in most patients within three months. Those with chronic or radicular pain require additional evaluation and multiple therapies for effective relief. Systemic illness and spinal compression require prompt intervention to prevent serious complications.

How to recognize and treat specific low back pain?

A wide variety of mechanical and non-mechanical disorders are associated with the clinical symptom of low back pain. Mechanical disorders are the cause of the vast majority of low back pain. Despite this frequency, the specific cause of mechanical low back pain can not be elucidated in spite of extensive diagnostic evaluation in a majority of individuals. Specific causes of low back pain are associated with less frequently occurring systemic illnesses including rheumatic, infectious, neoplastic, gynaecological and vascular disorders. The diagnostic process is more successful in identifying systemic disorders as the specific cause of low back pain. Non-surgical management is effective therapy with most patients with mechanical disorders of any form. Systemic illnesses require interventions directed specifically at healing the affected organ system.

Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.

Low-income populations have a lower prevalence of low back pain than high-income populations. Pathologic processes affecting the intervertebral disc are affected by genetic factors and degeneration of annular fibers. Historical and physical findings are not helpful in identifying damaged tissues in patients with nonspecific low back pain. Agency for Health Care Policy and Research guidelines for plain radiographs in the evaluation of low back pain are too sensitive and expose patients unnecessarily to ionizing radiation. Clinical entities reviewed in the literature include septic sacroiliitis, prognosis of metastatic spinal tumors, and low back pain in health care professionals. Epidural corticosteroid injections are useful for leg pain and sensory deficits early in the course of sciatica secondary to a herniated nucleus pulposus. Poor nutritional state increases the risk for postoperative infections for spinal fusion patients.

Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study.

OBJECTIVES: The CarboMedics, Duromedics, Sorin Bicarbon and the St. Jude Medical valves are bileaflet mechanical prostheses of modern but different design. Choosing a valve with the best hemodynamic profile is of clinical importance in patients with small ventricles and a small mitral annulus. METHODS: The hemodynamic performance of these valves in the mitral position was compared in 76 asymptomatic, ambulatory patients with normally functioning prosthesis and left ventricle, using Doppler echocardiography. Of the 76 patients studied, 22 had the CarboMedics, 16 had the Duromedics, 17 had the Sorin Bicarbon and 21 had the St. Jude prosthesis. The patients ages ranged from 18 to 81 years. There were 44 women and 32 men. The time from implantation to echocardiographic study ranged from 1 to 55 months. RESULTS: The echocardiographic study was performed earlier after surgery in the Sorin Bicarbon group. There was no significant difference in women/man ratio, incidence of atrial fibrillation, left ventricular or left atrial diameters between the four groups. The mean prosthesis size was significantly smaller for Sorin Bicarbon and Duromedics valves compared to the CarboMedics and the St. Jude valves (mean+/-SD, 27.2+/-1.3, 27.1+/-1.1 and 30.0+/-1.9 and 30.0+/-2.7 mm, respectively, P<0.001). Despite its smaller size the Sorin Bicarbon valve had significantly larger effective valve area by Doppler compared to the CarboMedics valve (290+/-40 vs 250+/-60 mm2, respectively, P=0.014). The ratio of effective valve area to prosthesis size was significantly larger for the Sorin Bicarbon valve when compared with any other type of prosthesis. CONCLUSIONS: (1) The Sorin Bicarbon bileaflet valve offered the best hemodynamic results that may be explained by the valve's large leaflet opening angle and small thickness of the leaflets. (2) Since the Sorin Bicarbon is the newest bileaflet valve, durability of this valve remains uncertain.

Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.

Epidemiologic studies report the prevalence of low back pain to vary from 7.6% to 37% in different populations. Genetic factors play an important role in the development of back pain and intervertebral disk degeneration in adults. An animal model of spinal fusion using osteoinductive growth factors has important implications for surgical spinal fusions in humans. Physical findings have significance in identifying patients with radiculopathy, spinal stenosis, and malingering. Magnetic resonance imaging differentiates metastatic spinal fractures from osteoporotic lesions. Clinical entities reviewed in the literature this year include herniated intervertebral disk-associated radiculopathy, facet joint syndrome, back pain during pregnancy, and spontaneous infectious diskitis. Primary care physicians do not follow published guidelines for treatment of low back pain. Surgical decompression of spinal stenosis is most successful for patients with severe disease.

A clinician's approach to acute low back pain.

Two important goals in treating acute low back pain are to return the patient to regular activity as quickly as possible and to do so in a manner that is cost-effective. By following a logical treatment protocol, the clinician is often able to provide the treatment necessary to provide the patient with relief. Referral to an orthopedist or neurosurgeon may be appropriate in only a minority of cases. Thus, after the initial history and physical examination, ruling out (or in) conditions that require urgent or emergent care is essential. These conditions include cauda equina syndrome, circulatory collapse due to expanding abdominal aortic aneurysm, and tumor, infection, and other underlying disorders as a cause of low back pain. Patients without these conditions can be started on conservative therapy-without radiographic or laboratory tests-regardless of the specific diagnosis. Conservative therapy consists of passage of time, controlled physical activity, physical modalities (e.g., cryotherapy or thermotherapy), local injections, nonsteroidal anti-inflammatory drugs, and muscle relaxants. Because low back pain is so common, even the small proportion of patients who do not improve after 6 weeks of conservative therapy represents a sizable number. The location and radiation of pain are used as initial guides to classifying these patients into four groups: those with localized pain, sciatica, anterior thigh pain, or posterior thigh pain. Each follows a different diagnostic path, which will be described herein.

Prevalence of spinal disc disease among interventional cardiologists.

A suspected, but undocumented, excess of axial skeletal disease among interventional cardiologists (possibly a consequence of lead apron use) was investigated by comparing questionnaire responses from cardiologists, orthopedic surgeons, and rheumatologists (n = 714). Cardiologists reported more neck and back pain, more subsequent time lost from work, and a higher incidence of cervical disc herniations, as well as multiple level disc disease (all p <0.01): "interventionalist's disc disease" is a confirmed entity.

Does managed care permit appropriate use of psychotherapy?

The author reviews the history of the development of managed care, the restrictions it has placed on psychiatric treatments, including psychotherapy, and the concerns it has raised about access to and quality of care. He discusses research studies documenting that psychotherapy is a fundamental component of psychiatric treatment and that it must be included in all health plans and organized systems of care. Several false beliefs about the use and cost of psychotherapy are considered, such as that dyadic psychotherapy is based on abreaction, a technique that Freud abandoned, and that costs for psychotherapy will skyrocket if it becomes universally accessible. Research has indicated that inappropriate limitations on psychotherapy in prepaid settings lead to poor mental health outcomes. The author emphasizes that cost-based constraints on established psychiatric treatments are not acceptable until carefully constructed scientific outcome studies demonstrate that the use of such constraints does not lead to adverse consequences.

Chronic low back pain.

Most episodes of low back pain are mechanical in origin and resolve within a 12-week period. These acute episodes of back pain are associated with muscle strain and intervertebral disc herniation with radiculopathy. A smaller proportion of individuals have back pain with a duration greater than 12 weeks. These patients have back pain secondary to a wide variety of mechanical and nonmechanical disorders. The mechanical disorders associated with chronic low back pain include osteoarthritis and lumbar spinal stenosis; the nonmechanical disorders include infectious, neoplastic, rheumatologic, endocrinologic, vascular, and gynecologic. The clinical symptoms associated with each variety of disorder helps guide the appropriate diagnostic evaluation. Plain roentgenograms are useful in documenting the presence of spinal stenosis, benign or malignant tumors, osteoporosis, sacroiliitis, and spondylitis. CT scan is helpful in defining the bony alterations associated with malignant tumors and the vascular abnormalities associated with aneurysms. MR imaging is the technique of choice to document the extent of malignant processes and the presence of endometriosis in the pelvis. The therapy of these entities are specific for the disease entity causing the chronic low back pain. Although most of the disorders that cause chronic low back pain cannot be cured, therapy can decrease pain and improve function of the symptomatic patient.

Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain.

Epidemiologic studies found mechanical low back pain to be the fifth most common reason for visiting a physician. Proteoglycan production is altered with the age of the host and may explain the development of degenerative disk disease. Important clinical low back pain entities reviewed in the literature include exercise-associated degenerative disk disease, sciatica in adults less than 21 years of age, fibromyalgia, apophyseal and sacroiliac joint pain, and sacral insufficiency fractures. No consensus exists among physicians concerning appropriate therapy for low back pain. Return to usual activity is the most effective therapy, according to a recent study. The first decompression operation for spinal stenosis has the best opportunity for a good outcome. Chiropractors are the most expensive health care providers for low back pain patients.