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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
New guidelines for management of gout (February 2017)
Several professional organizations have recently published guidelines for the management of gout, including the European League Against Rheumatism (EULAR) , an international task force , and the American College of Physicians (ACP) . The ACP guidelines depart from recommendations of the American College of Rheumatology (ACR), EULAR, the international task force, and others by suggesting a treat-to-avoid-symptoms approach (ie, monitoring the adequacy of urate-lowering drug dosing based on the frequency and severity of acute attacks) rather than a treat-to-target approach based on serum urate levels. We concur with the ACR, EULAR, and international guidelines groups, based upon the available clinical evidence and an understanding of the pathophysiology of gout, and we continue to recommend monitoring serum urate levels and using such data to make treatment choices and titrate dosing. (See "Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Recommendations of major groups'.)
Relative cardiovascular safety of celecoxib, naproxen, and ibuprofen (December 2016)
The cardiovascular (CV) safety of celecoxib, the COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), compared with other NSAIDs, is a matter of debate. In a randomized trial (PRECISION) involving over 24,000 patients with arthritis and either known CV disease or CV risk factors, the CV safety of celecoxib was noninferior to both naproxen and ibuprofen, two nonselective NSAIDs . Depending upon the analysis, about 2 to 5 percent of subjects experienced a CV event during follow-up, which was slightly lower than the expected event rate. Despite some limitations, this trial suggests that celecoxib in moderate doses can be administered, when indicated, without concern about increased CV risk compared with the nonselective nonsteroidal agents naproxen and ibuprofen. (See "COX-2 selective inhibitors: Adverse cardiovascular effects", section on 'Celecoxib' and "Nonselective NSAIDs: Adverse cardiovascular effects", section on 'Risk of myocardial infarction, stroke, and death'.)
ORTHOPEDICS, SPINE, AND SOFT TISSUE RHEUMATIC DISORDERS
Investigational autologous nasal chondrocyte grafts for articular cartilage defects (November 2016)
Replacing localized regions of degenerated cartilage with autologous chondrocytes grafts may be beneficial for selected patients with less severe, localized articular cartilage defects. There is an interest in using alternative sources of autologous chondrocytes with superior cartilage-forming capacity compared with articular chondrocytes. In a proof-of-concept, first-in-human trial, 10 patients with symptomatic, post-traumatic, full-thickness cartilage lesions on the femoral condyle or trochlea were treated with engineered tissue from autologous nasal cartilage . Significant improvements in pain, knee function, and quality of life were found during the 24-month follow-up period. These early data will need further validation to establish efficacy and appropriateness of this approach for treating articular cartilage defects. (See "Overview of surgical therapy of knee and hip osteoarthritis", section on 'Autologous chondrocyte implantation'.)
Vertebroplasty for osteoporotic compression fractures (November 2016)
The indications for and timing of vertebroplasty for the treatment of osteoporotic compression fractures are controversial. In a trial comparing vertebroplasty or simulated vertebroplasty (sham) in 120 patients with acute (less than six weeks) vertebral fracture and back pain, more patients in the vertebroplasty group achieved clinically significant lower pain scores at 14 days . Two previous sham-controlled trials, however, did not show a significant reduction in pain with vertebroplasty, likely due to differences in study design, including different sham procedures for the control arm and varying definitions of acute vertebral fracture. (See "Osteoporotic thoracolumbar vertebral compression fractures: Clinical manifestations and treatment", section on 'Vertebroplasty'.)
Treatment of degenerative meniscal tears (September 2016)
Acute meniscal tears often benefit from surgical treatment, but the appropriate management of chronic, degenerative tears, particularly in middle-aged adults, has been a source of debate. A recent trial randomly assigned 140 middle-aged adults (mean age 49.5) with a degenerative meniscal tear (and no evidence of osteoarthritis on magnetic resonance imaging [MRI]) to receive exercise therapy or partial meniscectomy . The trial found no clinically significant difference in knee function or pain at two years of follow-up. This finding is consistent with several other small randomized trials that have reported no clinically significant benefit from arthroscopic surgery in such patients. In the absence of persistent joint effusions or mechanical dysfunction, we suggest physical therapy as the initial management for middle-aged patients with degenerative meniscal tears. (See "Meniscal injury of the knee", section on 'Chronic degenerative meniscal injury'.)
Internet-delivered therapy for chronic knee pain (February 2017)
Nonpharmacologic interventions are known to be effective in the treatment of chronic knee pain and osteoarthritis (OA), but implementation of such therapies is often limited. In a trial of 148 adults with chronic knee pain and disability, patients were randomized to either a novel internet-based intervention or a control group . Both groups had access to internet-based educational material, but the intervention group also received interactive online training in pain-coping skills as well as videoconferencing sessions with a physiotherapist for home exercise. At three months, the intervention group reported improved pain and function compared with the control group, which was sustained for at least six months. More data are needed to evaluate internet-based strategies as a practical way to deliver care for OA patients. (See "Nonpharmacologic therapy of osteoarthritis", section on 'Patient education and psychosocial support'.)
Lack of benefit of chondroitin and glucosamine for knee osteoarthritis (January 2017)
The use of glucosamine and chondroitin for osteoarthritis (OA) has been controversial, with most studies showing little to no evidence of clinically meaningful benefit. In a multicenter randomized trial, 164 patients with moderate to severe knee osteoarthritis were treated with either placebo or chondroitin sulfate plus glucosamine . At six months' follow-up, the mean reduction in the global pain score was greater in the placebo group, and there were no between-group differences in patient-reported function or other outcomes. Although the study was limited by the small size and potentially inadequate dosing of chondroitin and glucosamine, it is likely that the combination of glucosamine and chondroitin is no better than placebo in patients with knee osteoarthritis. (See "Initial pharmacologic therapy of osteoarthritis", section on 'Glucosamine and chondroitin'.)
Effect of antihypertensive drug class on fracture rates (January 2017)
Thiazide diuretics stimulate distal tubular reabsorption of calcium, leading to a decrease in urinary calcium excretion and a possible benefit on bone mineral density. The rates of hip or pelvic fractures among patients treated with thiazide-like diuretics, angiotensin converting enzyme (ACE) inhibitors, or calcium channel blockers were compared in a post-hoc analysis of the ALLHAT trial . At approximately five years, those randomly assigned chlorthalidone had fewer hip or pelvic fractures as compared with those assigned to either lisinopril or amlodipine. Thus, if monotherapy is appropriate in a patient with hypertension and osteoporosis, thiazide-like diuretics may have advantages over ACE inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Thiazide diuretics'.)
Investigational parathyroid hormone-related peptide analog for postmenopausal osteoporosis (October 2016)
Abaloparatide is an investigational synthetic analog of parathyroid hormone-related peptide (PTHrP) that binds more selectively than parathyroid hormone 1-34 (teriparatide) to the PTH1 receptor, conferring a more transient response favoring bone formation and minimizing bone resorption and hypercalcemia. In a phase III trial, nearly 2500 postmenopausal women with osteoporosis were randomly assigned to abaloparatide, placebo, or open-label teriparatide . Compared with placebo, new radiographic vertebral fractures occurred less frequently in the abaloparatide and teriparatide groups. The incidence of hypercalcemia was lower with abaloparatide than teriparatide. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Emerging therapies'.)
Investigational monoclonal anti-sclerostin antibody for postmenopausal osteoporosis (September 2016)
Sclerostin is secreted by osteocytes and inhibits bone formation. Romosozumab, a monoclonal anti-sclerostin antibody under investigation for the treatment of osteoporosis, has been shown to improve bone density in postmenopausal women. In a trial specifically designed to assess radiographic vertebral fracture outcomes, 7180 postmenopausal women with osteoporosis were randomly assigned to romosozumab (210 mg subcutaneously once monthly) or placebo for 12 months . Thereafter, all women received denosumab (60 mg subcutaneously every six months) for an additional 12 months. The incidence of radiographic vertebral fracture was lower in the romosozumab group at 12 months (0.5 versus 1.8 percent) and 24 months (0.6 versus 2.5 percent). There was an increased frequency of injection site reactions in the romosozumab group. Ongoing trials should provide more information about safety and efficacy, including nonvertebral fracture reduction. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Emerging therapies'.)
Methotrexate for moderate oligoarticular juvenile idiopathic arthritis (February 2017)
Methotrexate is used as part of initial therapy in oligoarticular juvenile idiopathic arthritis (JIA) for those with severe disease activity and poor prognostic risk factors, but it is not clear if it should be used in patients with moderate disease. In a randomized, open-label trial of over 200 children with moderate oligoarticular JIA, the addition of oral methotrexate to glucocorticoid injections did not improve the proportion of children who achieved inactive disease or clinical remission at 12 months, although it did increase the time to flare (by approximately four months) . Further study is needed to determine if methotrexate should be used for the initial therapy of children with moderate-risk JIA, including whether oral methotrexate is as effective as subcutaneous administration in this setting. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Initial therapy'.)
Adjuvant glucocorticoids for initial treatment of Kawasaki disease (January 2017)
The use of glucocorticoids to treat children with Kawasaki disease has been a subject of debate. In a meta-analysis of comparative studies examining initial treatment with glucocorticoids plus intravenous immune globulin (IVIG) compared with IVIG alone, combination therapy was associated with a lower rate of coronary artery abnormalities, with the greatest benefit in patients predicted to be at high risk for IVIG resistance at baseline . The Kobayashi criteria can be used to determine this risk status in Japanese children but are not reliable in other populations. When increased risk for IVIG resistance cannot be determined, we do not recommend routine use of glucocorticoids for initial therapy. (See "Kawasaki disease: Initial treatment and prognosis", section on 'Glucocorticoids'.)
Adalimumab versus certolizumab pegol in rheumatoid arthritis with inadequate methotrexate response (March 2017)
The relative efficacy of the five available tumor necrosis factor (TNF) inhibitors has not been well studied in patients with rheumatoid arthritis (RA). Now, a randomized trial involving over 900 patients with active RA and an inadequate response to methotrexate (MTX) alone has directly compared the combination of MTX with either of two TNF inhibitors (adalimumab and certolizumab pegol) and found neither combination superior to the other . There was no difference between the groups in the proportion of patients achieving a clinical response at week 12, the number with low disease activity at week 104, other major clinical outcome measures, or adverse effects. We continue to suggest choosing a TNF inhibitor based on factors such as patient preferences regarding route of administration and frequency of treatment, comorbidities, and local regulatory and coverage constraints. (See "Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy", section on 'MTX plus TNF inhibitor'.)
SCLERODERMA AND OTHER SYSTEMIC RHEUMATIC DISEASES
Management of microvascular damage in systemic sclerosis (December 2016)
Vasoactive drugs are used for systemic sclerosis (SSc) patients with severe Raynaud phenomenon (RP) and digital ulcers. For prevention of recurrent digital ulcers, there may be a benefit from combination therapy with intravenous iloprost and bosentan. In a prospective observational study with 30 SSc patients receiving intravenous iloprost for severe secondary RP, half of the patients were also given bosentan following the development of digital ulcers or pulmonary arterial hypertension . After four years of follow-up, the iloprost plus bosentan group showed evidence of a significant improvement in digital microvasculature structure and function, which also corresponded with a significant reduction in the incidence of new digital ulcers. This limited study needs confirmation but suggests that combination therapy may be helpful in complex SSc patients with recurrent digital ulcers. (See "Treatment of the Raynaud phenomenon resistant to initial therapy", section on 'Recurrent digital ulcers in systemic sclerosis'.)
Mycophenolate mofetil for scleroderma lung disease (October 2016)
Cyclophosphamide has been the suggested treatment for moderate-to-severe interstitial lung disease complicating systemic sclerosis (SSc-ILD) but has well-known toxicity. A recent randomized trial compared mycophenolate mofetil (MMF) with oral cyclophosphamide in 142 patients with SSc-ILD, exertional dyspnea, and features of progressive disease . Pulmonary function and dyspnea improved in both groups, without a significant difference between groups. MMF was better tolerated than cyclophosphamide based on a longer time to patient withdrawal and lower incidence of leukopenia and thrombocytopenia. We now suggest initiating treatment for symptomatic progressive SSc-ILD with mycophenolate, rather than cyclophosphamide, due to comparable efficacy, better safety profile, and the option for longer-term therapy. (See "Treatment and prognosis of interstitial lung disease in systemic sclerosis (scleroderma)", section on 'Choice of an agent'.)
Guidelines for the treatment of systemic sclerosis (October 2016)
The British Society for Rheumatology (BSR) and the British Health Professionals in Rheumatology (BHSR) have published a comprehensive set of guidelines for the management of systemic sclerosis (SSc) . Some of the key points include the importance of making an early diagnosis and considering treatment with an immunosuppressive agent in patients with diffuse cutaneous SSc of less than three years' duration. They also review the major therapies for treating organ-based disease and emphasize the importance of referring patients to specialty centers with access to multidisciplinary care. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'General principles of management'.)
SYSTEMIC LUPUS ERYTHEMATOSUS AND SJOGREN'S SYNDROME
Accuracy of the spot urine protein to creatinine ratio in patients with kidney disease (October 2016)
A spot urine protein to creatinine ratio (UPCR) is frequently used to estimate 24-hour proteinuria and to follow the effects of treatment in patients with proteinuric kidney diseases. However, a longitudinal study of patients with biopsy-proven glomerular disease  and a systematic review of studies of patients with lupus nephritis  have demonstrated that a spot UPCR may not accurately predict the result of a 24-hour urine, particularly in patients with lower degrees (<1 g/day) of proteinuria. These findings support our recommendation that a 24-hour urine collection should be the method of choice for initial quantification of proteinuria and for verification of changes in proteinuria before therapy is altered in patients with kidney disease. (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults", section on 'Accuracy of spot urine estimates'.)
Anakinra for familial Mediterranean fever (January 2017)
Anti-interleukin (IL)-1 therapy has been the preferred second-line therapy for patients with familial Mediterranean fever (FMF) based on data from case reports and case series. In the first randomized trial to evaluate anti-IL-1 therapy in colchicine-resistant FMF, 24 patients from a single center received daily injections of either anakinra or placebo and were followed for four months . Patients in the anakinra group had fewer attacks per month, significant improvement in quality of life, and no severe adverse events. Thus, anakinra appears to be a safe and effective alternative for patients who do not respond to or cannot tolerate colchicine. (See "Management of familial Mediterranean fever", section on 'Interleukin-1 inhibition'.)
Adalimumab for noninfectious uveitis (November 2016)
Patients with noninfectious uveitis can benefit from effective and safe glucocorticoid-sparing therapy. Two well-designed, randomized trials showed that adalimumab was effective in the treatment of noninfectious intermediate, posterior, and pan-uveitis [22,23]. In these trials, adalimumab improved the time-to-treatment failure in patients with uveitis who followed a tapering schedule for oral glucocorticoids. Both the European Medicines Agency and the US Food and Drug Administration recommended approval of adalimumab for adults with these forms of uveitis. (See "Uveitis: Treatment", section on 'Anti-tumor necrosis factor-alpha'.)
- Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017; 76:29.
- Kiltz U, Smolen J, Bardin T, et al. Treat-to-target (T2T) recommendations for gout. Ann Rheum Dis 2016.
- Qaseem A, Harris RP, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2017; 166:58.
- Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med 2016; 375:2519.
- Mumme M, Barbero A, Miot S, et al. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. Lancet 2016; 388:1985.
- Clark W, Bird P, Gonski P, et al. Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2016; 388:1408.
- Kise NJ, Risberg MA, Stensrud S, et al. Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients: randomised controlled trial with two year follow-up. BMJ 2016; 354:i3740.
- Bennell KL, Nelligan R, Dobson F, et al. Effectiveness of an Internet-Delivered Exercise and Pain-Coping Skills Training Intervention for Persons With Chronic Knee Pain: A Randomized Trial. Ann Intern Med 2017.
- Roman-Blas JA, Castañeda S, Sánchez-Pernaute O, et al. Combined Treatment With Chondroitin Sulfate and Glucosamine Sulfate Shows No Superiority Over Placebo for Reduction of Joint Pain and Functional Impairment in Patients With Knee Osteoarthritis: A Six-Month Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Arthritis Rheumatol 2017; 69:77.
- Puttnam R, Davis BR, Pressel SL, et al. Association of 3 Different Antihypertensive Medications With Hip and Pelvic Fracture Risk in Older Adults: Secondary Analysis of a Randomized Clinical Trial. JAMA Intern Med 2017; 177:67.
- Miller PD, Hattersley G, Riis BJ, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA 2016; 316:722.
- Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med 2016; 375:1532.
- Ravelli A, Davì S, Bracciolini G, et al. Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial. Lancet 2017.
- Chen S, Dong Y, Kiuchi MG, et al. Coronary Artery Complication in Kawasaki Disease and the Importance of Early Intervention : A Systematic Review and Meta-analysis. JAMA Pediatr 2016; 170:1156.
- Smolen JS, Burmester GR, Combe B, et al. Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study. Lancet 2016; 388:2763.
- Trombetta AC, Pizzorni C, Ruaro B, et al. Effects of Longterm Treatment with Bosentan and Iloprost on Nailfold Absolute Capillary Number, Fingertip Blood Perfusion, and Clinical Status in Systemic Sclerosis. J Rheumatol 2016; 43:2033.
- Tashkin DP, Roth MD, Clements PJ, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 2016; 4:708.
- Denton CP, Hughes M, Gak N, et al. BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford) 2016; 55:1906.
- Hogan MC, Reich HN, Nelson PJ, et al. The relatively poor correlation between random and 24-hour urine protein excretion in patients with biopsy-proven glomerular diseases. Kidney Int 2016; 90:1080.
- Medina-Rosas J, Yap KS, Anderson M, et al. Utility of Urinary Protein-Creatinine Ratio and Protein Content in a 24-Hour Urine Collection in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis. Arthritis Care Res (Hoboken) 2016; 68:1310.
- Ben-Zvi I, Kukuy O, Giat E, et al. Anakinra for colchicine resistant familial Mediterranean fever - A randomized, double blind, placebo-controlled trial. Arthritis Rheumatol 2016.
- Jaffe GJ, Dick AD, Brézin AP, et al. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med 2016; 375:932.
- Nguyen QD, Merrill PT, Jaffe GJ, et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet 2016; 388:1183.