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EULAR 2015 Annual European Congress of Rheumatology Rome, Italy, 10-13 June

Triple DMARD induction regimen is ‘more effective’ than MTX monotherapy in early RA

Starting rheumatoid arthritis (RA) patients with early RA on triple-combination therapy with disease-modifying anti-rheumatic drugs (DMARDs), rather than escalating therapy with a step-wise approach, significantly improves disease activity and functional ability over two years, a Dutch study presented at the 2015 European League Against Rheumatism (EULAR 2015) Congress in Rome, Italy, suggests.

Results of the treatment in the Rotterdam Early Arthritis CoHort (tREACH) trial also suggest that an initial regimen of methotrexate (MTX), sulfasalazine and hydroxychloroquine, as well as a ‘bridging’ glucocorticoid, provides substantial and earlier benefits than MTX monotherapy (with glucocorticoid).

Moreover, the study shows that patients starting out on combination DMARD therapy “reach their targets earlier… and could taper their medications earlier than those on monotherapy,” said lead author Dr Angelique Weel, Department of Rheumatology, Maasstad Hospital in the Netherlands.

Such early and intensive treatment is not widely used in RA due to worries about side-effects, according to Dr Weel. “But we have already showed within our study, and in other studies, that the side-effects are not higher in the combination therapy compared to monotherapy with MTX.” The incidence of RA flares was also similar.

In the tREACH trial, 281 patients with early RA (68 per cent female) were randomised to the triple DMARD therapy or to MTX monotherapy.

The endpoint was a disease activity in 44 joints (DAS44) score of less than 1.6 at two consecutive time points.

DMARDs, either synthetic and/or biologic, were tapered in a stepwise fashion after a median of nine months if DAS44 was below 1.6 at two consecutive time points, according to the study abstract.

After just three months, the triple-therapy group achieved greater improvements in functional ability, seen in Health Assessment Questionnaire (HAQ) scores, than the MTX group. Results remained significant throughout the two years, irrespective of disease activity.

Similar percentages in both groups (51 per cent vs 47 per cent) achieved sustained remission and were able to taper their medications at six or 24 months, displaying minimal progression of joint damage on x-rays; 11 per cent of patients had drug-free remission at two years.

Exacerbation of symptoms (prevalence of flares) after tapering medication was similar between the combination and monotherapy groups.

NSAIDs significantly inhibit ovulation in women with mild musculoskeletal pain after just 10 days

The results of a study presented at EULAR 2015 show that diclofenac, naproxen and etoricoxib significantly inhibit ovulation in women with mild musculoskeletal pain. Of the studied women receiving NSAIDs, only 6.3 per cent (diclofenac), 25 per cent (naproxen) and 27.3 per cent (etoricoxib) ovulated, compared with 100 per cent of the control group.

“After just 10 days of treatment we saw a significant decrease in progesterone, a hormone essential for ovulation, across all treatment groups, as well as functional cysts in one-third of patients,” said study investigator Prof Sami Salman, Department of Rheumatology, University of Baghdad, Iraq. “These findings show that even short-term use of these popular, over-the-counter drugs could have a significant impact on a woman’s ability to have children. This needs to be better communicated to patients with rheumatic diseases, who may take these drugs on a regular basis with little awareness of the impact.”

Thirty-nine women of childbearing age who experienced back pain took part in the study, and received diclofenac (100mg once daily), naproxen (500mg twice daily) and etoricoxib (90mg once daily) or placebo. Treatment was given for 10 days from day 10 of the onset of the menstrual cycle; hormonal analysis (progesterone level) and follicle diameter were conducted via blood sample and ultrasonography, respectively.

At the end of the NSAID treatment period, the dominant follicle remained unruptured in 75 per cent, 25 per cent and 33 per cent of patients receiving diclofenac, naproxen and etoricoxib, respectively. Rupturing of the dominant follicle, and subsequent release of an oocyte, is essential for ovulation to occur.

NSAIDs are among the most commonly-used drugs worldwide and are taken by more than 30 million people every day.

Physical trauma is associated with the onset of psoriatic arthritis among psoriasis patients

The results of a large population study presented at EULAR 2015 showed an increased risk of developing psoriatic arthritis (PsA) among psoriasis patients exposed to physical trauma, particularly when the trauma involved bone and/or joints.

Psoriasis occurs in 1-to-3 per cent of the population, with PsA occurring in up to 30 per cent of those cases. Trauma had previously been found to be associated with PsA in smaller studies, which in turn had led to the idea of a ‘deep Koebner’ phenomenon playing a role in PsA, mirroring the superficial Koebner phenomenon seen in skin psoriasis. Koebner found that when an area of skin in people with psoriasis became traumatised following injury, a psoriatic lesion often appeared in the same location.

Using data collected between 1995 and 2013, 15,416 psoriasis patients exposed to trauma and 55,230 unexposed controls were identified by the Icelandic study and followed-up, with 1,010 PsA cases recorded.

The incidence rate of PsA among psoriasis patients not exposed to trauma was 22 per 10,000 person-years, compared to 30 per 10,000 person-years in the exposed group.

Following adjustments for age, gender, date of entry into the patient database, duration of psoriasis, BMI, smoking, alcohol consumption and number of visits to the GP, psoriasis patients exposed to trauma were shown to have an increased risk of PsA compared to controls (hazard ratio, 1.32).

A subset analysis showed that while bone and joint traumas were associated with increased PsA risk (hazard ratios, 1.46 vs 1.50 respectively), nerve trauma and skin trauma were not. Patients without psoriasis exposed to trauma did not have an increased risk of developing RA (hazard ratio, 1.04).

“This is the first sizable, population-based cohort study to determine the risk of PsA following trauma in psoriasis patients,” said Dr Thorvardur Love, senior author, from Landspitali University Hospital, Iceland.

“Our findings highlight the importance of further study into the complex factors that lead to arthritis in psoriasis patients, as we may find ways to modify the risk once we fully understand it,” he added.

Childhood infections and low birth weight shown to predict risk of ankylosing spondylitis

A diagnosis of ankylosing spondylitis (AS) can be predicted by low birth weight, having older siblings and hospitalisation for infection between the ages of five-to-16 years, a new Swedish study, presented at EULAR 2015, has found.

Statistically significant increased risks were observed for birth weight under 3,000g (18 per cent vs 15 per cent), having older siblings (63 per cent vs 58 per cent) and for hospitalisation due to infections at age 5-to-12 (5 per cent vs 3 per cent) and age 13-to-16 (2 per cent vs 1 per cent). These factors have been implicated in other associated disease; the triggering effect of infections in reactive arthritis has been established, birth weight has been shown to predict development of autoimmune disease (diabetes and RA), and a link between older siblings and disease risk has been demonstrated in asthma.

The study suggests that these factors play an important role in the pathogenesis of the disease, the cause of which is unknown. Although AS is strongly associated with the genotype HLA-B27, not everyone testing positive for the marker goes on to develop the disease.

“A link between AS and the HLA-B27 genotype was established more than three decades ago, yet studies on the environmental risk factors are few,” said study investigator Dr Ulf Lindström, Institute of Medicine, Rheumatology and Inflammation Research, Sahlgrenska Academy, Sweden. “Our research has identified three factors associated with significantly increased risk of the disease in later life. These data strengthen our understanding of the interplay between genetics and environment in AS, and bring us closer to pinpointing the underlying cause of the disease.”

Data from several Swedish national registers were used for this study, with five matched controls identified for each case of AS. Exposures assessed were birth weight, gestational age, type of birth (single/multiple), number of older siblings and exposure to infections.

Anti-TNFs cost could be reduced

A good clinical response to anti-TNF maintenance treatment in RA patients was maintained, even when the dose was reduced by one-third, which could mean significant savings, the results of a study presented at EULAR 2015 showed.

However, reducing the anti-TNF dose by two-thirds resulted in more flares but these subsided when the higher dose of anti-TNF was restarted, and did not adversely affect subsequent progression of any disability. In some cases, patients maintained a clinical response after stopping the anti-TNF altogether.

The OPTTIRA study is a 12-month, multicentre, randomised, controlled trial designed to evaluate if reducing anti-TNF doses (of either etanercept or adalimumab) caused a loss of response in RA patients who were also receiving a synthetic DMARD. To be eligible, patients had to demonstrate stable low disease activity (DAS28 less than 3.2) for over three months. Patients with serious concomitant illness or those taking high-dose steroids (more than 10mg prednisolone daily) were excluded.

Over the first six months of the study, flares (exacerbations of symptoms and signs) occurred in 14 per cent of patients who stayed on the same anti-TNF dose, compared to a similar figure of 13 per cent in those patients for whom the dose was reduced by one-third.

A two-thirds dose reduction increased the odds of a flare occurring by four times, compared with a one-third dose reduction, with flares occurring in 37 per cent of patients. Post-dose reduction flares resolved when the original anti-TNF dose was restarted. There were no significant differences in self-reported measures of disability (HAQ score) with either dose reduction strategy at six months.

Of the 47 patients who reduced, then stopped their anti-TNF after six months, 45 per cent (21/47) succeeded without flaring, and their final mean DAS28 score after stopping treatment was 2.2, demonstrating low disease activity.

“The optimal management of RA involves achieving the lowest possible disease activity — ideally remission and then maintaining this level of control,” said lead author Dr James Galloway, Department of Rheumatology, King’s College Hospital NHS Foundation Trust, UK.

“Findings from our study have shown that adopting an anti-TNF dose reduction strategy can still meet this objective, with no compromise on symptom control for the patient and offering a more cost-effective option by substantially reducing the high drug costs associated with anti-TNF maintenance therapy.”

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