Editorial; April 28, 2015; from: The Genetics of Rheumatoid Arthritis

New Insights and Implications

David T. Felson, MD, MPH1,2; Lars Klareskog, MD, PhD3

[+] Author Affiliations

JAMA. 2015;313(16):1623-1624. doi:10.1001/jama.2015.1710. 

Rheumatoid arthritis (RA) is a common disabling systemic inflammatory disorder that causes chronic joint destruction. However, by most assessments, the consequences of treated disease have become less severe during the past 20 years. An armamentarium of second-line drugs, including methotrexate and biologic agents such as tumor necrosis factor (TNF) inhibitors, in combination with widely accepted treatment strategies, which include early treatment and treatment that targets low disease activity,1 has led to a reduction in disease activity for patients with RA throughout much of the developed world.2 Despite highly effective treatments, approximately 20% of patients continue to experience pain, disability, and joint destruction. In addition, even with effective treatment, RA has been linked to increased cardiovascular mortality,3 perhaps because of long-standing high levels of systemic inflammation. The residual disease activity among patients whose disease is difficult to manage and the associated cardiovascular mortality remain important management challenges.

Opioid Analgesics for Rheumatoid Arthritis Pain

Samuel L. Whittle, MBBS, MClinEpi; Bethan L. Richards, MBBS, MClinEpi; Rachelle Buchbinder, MBBS, PhD

JAMA. 2013;309(5):485-486. doi:10.1001/jama.2012.193412.

Clinical Question Do the benefits of opioid analgesics outweigh the risks in patients with persistent pain due to rheumatoid arthritis?

Bottom Line Weak opioids (such as codeine, dextropropoxyphene, and tramadol) may be effective in the short-term management of rheumatoid arthritis pain, but adverse effects are common and may outweigh the benefits; alternative analgesics should be considered first.

Risk of Malignancies in Patients With Rheumatoid Arthritis Treated With Biologic Therapy: A Meta-analysis

Maria A. Lopez-Olivo, MD, PhD; Jean H. Tayar, MD; Juan A. Martinez-Lopez, MD; Eduardo N. Pollono, MD; Jose Polo Cueto, MD; M. Rosa Gonzales-Crespo, MD; Stephanie Fulton, MSIS; Maria E. Suarez-Almazor, MD, PhD

JAMA. 2012;308(9):898-908. doi:10.1001/2012.jama.10857.

Context Concerns exist regarding the potential development of malignancies in patients with rheumatoid arthritis (RA) who are receiving biologic response modifiers (BRMs).

Objective To assess the risk of malignancy in patients with RA enrolled in randomized controlled trials (RCTs) of BRMs.

Data Sources Electronic databases, conference proceedings, and websites of regulatory agencies were searched for RCTs evaluating abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab in RA from inception through July 9, 2012.

Study Selection Independent selection of studies included RCTs that compared the safety of any BRMs used in RA patients with placebo and/or any traditional disease-modifying antirheumatic drugs with a minimum of 24 weeks of follow-up.

Data Extraction Independent reviewers selected studies and extracted data on quality and outcomes. Pooled estimates and 95% confidence intervals were calculated for each BRM.

Results Sixty-three RCTs with 29 423 patients were analyzed. No statistically significant increased risk of developing malignancy was observed. Of the 29 423 patients, 211 developed a malignancy during the trial (118 solid tumors, 48 skin cancers, 14 lymphomas, 5 hematologic nonlymphomas, and 26 not specified). The incidence rate for any malignancy during the first year of therapy was very low in the BRM plus methotrexate group (0.77%; 95% CI, 0.65%-0.92%), the BRM monotherapy group (0.64%; 95% CI, 0.42%-0.95%), and the controls (0.66%; 95% CI, 0.52%-0.84%). Anakinra plus methotrexate showed lower odds compared with methotrexate alone (Peto odds ratio, 0.11; 95% CI, 0.03-0.45). No statistically significant risk was observed for specific cancer sites, although the Peto odds ratio for lymphoma was 2.1 (95% CI, 0.55-8.4) in patients receiving tumor necrosis factor inhibitors compared with controls.

Conclusion The use of BRMs among patients with RA included in RCTs of at least 6 months' duration was not significantly associated with an increased risk of malignancy compared with other disease-modifying antirheumatic drugs or with placebo.

News From the Centers for Disease Control and Prevention; December 25, 2013

Limitations From Arthritis Pain Exceed Previous Estimate

JAMA. 2013;310(24):2607. doi:10.1001/jama.2013.284155.

Arthritis pain is keeping more US adults from pursuing everyday activities, sports, or hobbies than earlier projections had estimated, according to recent data from the National Health Interview Survey (NHIS).

Researchers used NHIS data for 2010 to 2012 to determine the prevalence of arthritis and arthritis-related activity limitations among US adults and compare those figures with previous estimates. Currently, 52.5 million US adults—22.7% of men and women aged 18 years or older—report having arthritis that was diagnosed by a physician. Of them, 22.7 million, or 43.2%, said arthritis pain has restricted their activities.

News From the Centers for Disease Control and Prevention; January 20, 2015

Veterans Have Higher Arthritis Rates Than Civilians

JAMA. 2015;313(3):236. doi:10.1001/jama.2014.17592.

Arthritis affects at least a quarter of military veterans, according to a new study that for the first time included both women and men in the US armed services (Murphy LB et al. MMWR Morb Mortal Wkly Rep. 2014;63[44]:999-1003).

The investigators analyzed Behavioral Risk Factor Surveillance System data from nearly 1.3 million civilians and about 112 000 veterans who participated in the surveys in 2011 through 2013. They found that 25.6% of veterans reported having arthritis compared with 23.6% of adults who had not served in the military. Female veterans had a higher incidence of arthritis—31.3%—than male veterans, 25%. Although men with a history of military service had more arthritis at every age compared with civilian men, arthritis rates were higher among young (aged 18-44 years) and middle-aged (aged 44-64 years) female veterans compared with civilian women.


To Vegan Diet, Rheumatoid Arthritis and Gut Flora

J Kjeldsen-Kragh. Rheumatoid arthritis treated with vegetarian diets. Am J Clin Nutr. 1999 Sep;70(3 Suppl):594S-600S.

R Peltonen, WH Ling, O Hänninen, E Eerola. An uncooked vegan diet shifts the profile of human fecal microflora: computerized analysis of direct stool sample gas-liquid chromatography profiles of bacterial cellular fatty acids. Appl Environ Microbiol. 1992 Nov;58(11):3660-6.

J Kjeldsen-Kragh, T Rashid, A Dybwad, M Sioud, M Haugen, O Førre, A Ebringer. Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet. Ann Rheum Dis. 1995 Mar;54(3):221-4.

A Ebringer, T Rashid. Rheumatoid arthritis is caused by a Proteus urinary tract infection. APMIS. 2014 May;122(5):363-8.

A Ebringer, T Rashid. Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper. Front Biosci (Elite Ed). 2009 Jun 1;1:577-86.

MT Nenonen, TA Helve, AL Rauma, OO Hänninen. Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. Br J Rheumatol. 1998 Mar;37(3):274-81.

R Peltonen, M Nenonen, T Helve, O Hänninen, P Toivanen, E Eerola. Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet. Br J Rheumatol. 1997 Jan;36(1):64-8.

R Peltonen, J Kjeldsen-Kragh, M Haugen, J Tuominen, P Toivanen, O Førre, E Eerola. Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet. Br J Rheumatol. 1994 Jul;33(7):638-43.

C Wilson, H Tiwana, A Ebringer. Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity. Microbes Infect. 2000 Oct;2(12):1489-96.

A Ebringer, T Rashid. Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection. Clin Dev Immunol. 2006 Mar;13(1):41-8.

A Ebringer, T Rashid. Rheumatoid arthritis is linked to Proteus--the evidence. Clin Rheumatol. 2007 Jul;26(7):1036-43.

H Adlercreutz, T Fotsis, C Bannwart, K Wähälä, T Mäkelä, G Brunow, T Hase. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J Steroid Biochem. 1986 Nov;25(5B):791-7.

BW Senior, GA Anderson, KD Morley, MA Kerr. Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Proteus mirabilis bacteriuria more frequently than healthy controls. J Infect. 1999 Mar;38(2):99-106.

L Guilherme, J Kalil. Rheumatic fever: from sore throat to autoimmune heart lesions. Int Arch Allergy Immunol. 2004 May;134(1):56-64.

L Guilherme, J Kalil, M Cunningham. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. 2006 Feb;39(1):31-9.

G Furneri, LG Mantovani, A Belisari, M Mosca, M Cristiani, S Bellelli, PA Cortesi, G Turchetti. Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis. Clin Exp Rheumatol. 2012 Jul-Aug;30(4 Suppl 73):S72-84.

M Saleem, HJ Kim, MS Ali, YS Lee. An update on bioactive plant lignans. Nat Prod Rep. 2005 Dec;22(6):696-716.

Content from across the British Medical Journal (BMJ) to celebrate World Lupus Day 

We've selected a number of our products to showcase in celebration of World Lupus Day, 10 May 2014. Read on for free articles from our world-renowned journals and free access to a lupus module from BMJ Learning, as well as an exclusive offer from Lupus Science & Medicine, the first Open Access lupus journal. Please share this with friends and colleagues to help spread awareness of lupus.

Lupus Science & Medicine: the first lupus-specific Open Access journal in the world

Lupus Science & Medicine is a global, peer reviewed, Open Access journal providing a central point for publication of basic, clinical, translational and epidemiological studies of all aspects of lupus and related diseases. It is an official journal of the Lupus Foundation of America (LFA), which is dedicated to advancing the science and medicine of lupus while offering support to patients and their caregivers.

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