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2014 ACR/AHRP Annual Meeting November 15-19, Boston, USA

Choice of contraception may influence rheumatoid arthritis autoimmunity risk

Women using intrauterine devices (IUDs) may be at increased risk for producing autoantibodies related to the risk of developing rheumatoid arthritis (RA), according to new research findings presented this week at the 2014 American College of Rheumatology (ACR) Annual Meeting in Boston, US.

The disease typically affects women three times as often as men.

In research from the ‘Studies of the Etiology of RA (SERA)’ project, researchers in Colorado, Nebraska, California, New York and Washington looked at the potential effects of different contraceptive use on blood levels of RA-related autoantibodies to citrullinated protein antigens (ACPA). In this study, ACPA testing included the anti-cyclic citrullinated peptide (anti-CCP) test. Elevated levels of anti-CCP can be found in the blood several years before joint symptoms develop in RA.

Having elevated anti-CCP levels strongly predicts future development of joint disease and a diagnosis of RA, and recent data suggest that ACPA may be directly pathogenic. Prior research suggests that hormonal factors may make women more susceptible to RA development than men.

From the SERA project, the researchers studied 976 women who had a first-degree relative with RA and who are therefore at increased risk for future RA, based on family history of RA. The researchers found that women who were currently using an IUD had a statistically significantly increased risk for anti-CCP positivity. There was also a trend toward a decreased risk of anti-CCP positivity in women who used oral contraceptive pills (OCPs), either currently or in the past. The researchers found no significant association between anti-CCP positivity and pregnancy or breastfeeding.

“We think these findings are very exciting and will lead to future studies that improve our understanding of RA development in women,” said Dr Kristen Demourelle of the University of Colorado Denver and a lead author of the study. “However, it is important to remember that this study was performed in a group of women already known to be at increased risk for RA. These findings may not apply to the general population and additional studies of women over a longer period of time are needed to confirm and extend these findings.

“Furthermore, not all women who were anti-CCP positive had used IUDs, so there are likely other factors related to the generation of these autoantibodies and this will also need to be explored.”

Further study is needed to determine which mechanisms may play a role in OCP use protecting against RA-related autoimmunity, the authors said.

Dose reduction of TNF inhibitors described as safe and effective for treating some RA patients

Carefully employing a TNF inhibitor dose-reduction strategy can be just as effective at safely treating rheumatoid arthritis (RA) patients as regular dosing methods, while also saving money, new research findings presented at the 2014 ACR Annual Meeting found.

In an 18-month study called DRESS (Dose Reduction Strategies of Subcutaneous TNF inhibitors), researchers in the Netherlands studied 180 RA patients who had low disease activity and were using either adalimumab or etanercept. The study’s primary goal was to assess whether a strategy — including carefully reducing the dose until stopping it and increasing treatment again when the RA became more active — produces results that are as effective/non-inferior as continuing the regular dosing of TNF inhibitors.

“If this approach to individualised dose optimisation could be proven to be as effective and safe as regular continuation of the drug, this would have a large impact on adverse drug reactions and costs in the millions of patients currently using these drugs,” said Dr Noortje van Herwaarden of Sint Maartenskliniek in the Netherlands and a lead author on the study.

In the study, the patients were randomised (two-to-one) to either a dose-reduction strategy or usual care, both in tight control settings.

The dose-reduction strategy consisted of increasing the interval between injections every three months until the patient flared or the drug was discontinued. If a patient had a flare, TNF inhibitors were either restarted or escalated, and no further dose optimisation attempts were made. A flare was defined as a DAS28-CRP increase >1.2, or DAS28-CRP increase >0.6 and current DAS28-CRP ≥3.2, compared to baseline. A persistent flare (the primary outcome) was defined as a flare lasting 12 weeks or more.

During the 18 months of follow-up, data were collected on DAS28-CRP scores, physical function, health-related quality of life, RA medication use and costs (including work loss, outpatient visits and travel costs).

The primary outcome was the difference in proportions of patients with persistent flare between the two groups, with a difference of less than 20 per cent defined as ‘non-inferiority’.

In the dose reduction group, the researchers found that TNF inhibitors could successfully be stopped in 20 per cent of the patients. They also found that the interval could be successfully increased in 43 per cent of the patients. In 37 per cent of the patients, no dose reduction was possible. Incidence and nature of serious adverse events were similar between groups. Costs were significantly lower in the dose-reduction group (mean difference per patient was estimated at €9,000 for the 18-month period).

The study’s authors concluded that a simple, tight-control TNF inhibitor dose-reduction strategy is non-inferior to usual care in maintaining disease control, function and quality of life and radiological disease control in RA patients with low disease activity. This strategy may help reduce healthcare costs in this population.

“The results from the DRESS study can have a tremendous impact on optimising RA TNF inhibitor treatment, as it has now been demonstrated that the same treatment results can be obtained with nearly 50 per cent reduction in medication exposure and costs. As the yearly revenues for adalimumab and etanercept alone (not taking into account the other biologics used in rheumatic diseases) exceeds US$20 billion (€16.1 billion) and is still growing, implementation of the DRESS findings could result in improved cost-effectiveness of the use of these biologics,” said Dr van Herwaarden.

Antibiotic use is associated with an increased risk of JIA

Use of antibiotics is associated with an increased risk of children developing juvenile idiopathic arthritis (JIA), according to new research findings presented at the 2014 ACR Annual Scientific Meeting in Boston.

Researchers at the University of Pennsylvania in Philadelphia, Nemours AI duPont Hospital for Children in Wilmington, Delaware, and Rutgers Biomedical and Health Sciences in Newark, New Jersey, conducted a case-control study using data from The Health Improvement Network, a UK population-based medical records database with comprehensive diagnostic and outpatient prescription data.

The research team identified 153 children diagnosed with JIA. Antibiotic exposure was associated with an increased risk of developing JIA after adjusting for confounders (adjusted odds ratio 2.6, 95 per cent CI 1.5, 4.6). This risk increased with each additional prescription. These results did not significantly change when adjusting for the number or type of infections. Age of exposure did not significantly modify this association.

The researchers found a relationship between antibiotics and newly diagnosed JIA that was similar across different antibiotic classes, although notably, use of non-bacterial antimicrobial agents (such as antifungal or antiviral drugs) was not associated with JIA. In order to ensure that the main finding was not just due to early symptoms of JIA, sensitivity analyses excluding data up to 12 months before the index date, the association between antibiotics and new diagnosis of JIA did not substantively change.

The study’s authors concluded that antibiotic exposure was associated with the development of JIA in a large population of children. This association was stronger for children exposed to multiple courses of antibiotics and appeared specific to antibacterial drugs alone. This study suggests that there is a role for antibiotic exposure in JIA disease pathogenesis, perhaps mediated through alteration in the microbiome.

“This study adds to a growing literature on the potential harms of antibiotic use in children. While antibiotics are certainly essential to treating some infections, these drugs are also over-prescribed for other infections (frequently respiratory) that will usually resolve without treatment,” said Dr Daniel Horton of Nemours and a lead author of the study. “If the link between antibiotics and JIA can be confirmed, antibiotic avoidance (in the right clinical situation) might be one of the few ways we have to prevent this life-changing disease. We still need to understand more about the biology that connects antibiotics, infections, the microbiome, genetics and chronic arthritis in children.

“Additional research in this area may also lead to novel ways of preventing and treating juvenile arthritis, similar to what is emerging now for inflammatory bowel disease.”

Exercise and manual therapy may improve pain and function in OA

Patients with hip and knee osteoarthritis (OA) may improve their pain, stiffness and physical function with sustained physical exercise, manual therapy or both, data presented at the 2014 ACR Annual Meeting revealed.

Existing evidence supports the effectiveness of exercise and manual therapy for easing hip and knee OA symptoms and improving physical function. However, no data existed to compare the addition of these treatment approaches to usual medical care for OA or for the long-term efficacy of this holistic approach. Researchers in New Zealand studied 206 OA patients for two years to measure the efficacy of adding regular physical exercise, manual therapy, or a combination of both therapies to standard care, versus continuing usual medical care for OA alone.

The participants’ progress was measured using the Western Ontario and McMaster (WOMAC) OA index, which calculates scores on a scale of 0-240. Lower WOMAC scores indicate improvements in pain, stiffness and physical function. Participants were also given several physical performance tests — ‘timed up-and-go’, 40-metre fast-paced walk and a 30-second sit-to-stand. At baseline, the mean age of the OA patients in the study was 66 years, with a mean WOMAC score of 100.8.

After two years, all the participants who engaged in either regular exercise, manual therapy or a combination of both showed improved WOMAC scores that were superior to those who had only the usual medical care for OA. Participants receiving exercise therapy in addition to their usual care showed improvement of 31.7 WOMAC points compared to usual care alone. Participants receiving manual therapy in addition to their usual care showed a relative improvement of 30.1 WOMAC points.

While the difference in WOMAC improvement for participants receiving combined exercise therapy and manual therapy in addition to usual care did not meet the a priori threshold for clinical significance (28 points), there was a trend towards benefit, with this group improving 26.2 WOMAC points more than usual care only. Those participants in the exercise therapy group showed greater mean changes on most physical performance tests than anyone in the other groups.

Adding either exercise therapy or manual therapy to usual medical care is beneficial for people with hip and knee OA, the study’s authors concluded: “This study showed that benefits imparted by a comprehensive programme of exercise therapy or manual therapy, provided by physical therapists, remain significant to at least two years follow-up,” said J Haxby Abbott, lead author.

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