Doctor's Review: Medicine on the Move

December 11, 2017

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2013 Annual Meeting of the ACR and ARHP

Boning up

About 16,000 rheumatologists and associated professionals converged upon Washington, DC's Walter E. Washington Convention Center this past November for the 2012 meeting of the American College of Rheumatology (ACR) and the Association of Rheumatology Health Professionals (ARHP).

Keeping up with the pace of change in rheumatology takes effort. Rheumatologists already refer to everything that happened more than a decade ago as the “pre-biologic era.” The biologic tumour necrosis inhibitors (anti-TNF drugs) have revolutionized treatment, raising both hopes of lasting remission and fears of lethal long-term side effects. Some of these lingering questions were settled at ACR 2012 and not a moment too soon; a new slew of drugs are entering the field, notably the Janus kinase (JAK) inhibitors.

Biologics acquitted on all charges

Following the real-world progress of the TNF inhibitors has been a worldwide effort and the assembled rheumatologists heard reassuring data pouring in from Ireland, Britain and Canada.

Anti-TNF therapy does not, contrary to long-held suspicions, increase the risk of lymphoma. Dr Louise Mercer of the University of Manchester reported, "there is no evidence that anti-TNF therapy increases the risk of lymphoma over the background risk associated with rheumatoid arthritis." Her British prospective study, based on 80,000 patient-years of follow-up in the UK, confirms findings from three previous observational studies. It strongly suggests that the warning label that comes with these drugs is actually wrong.1

In a separate study, Dr Mercer and colleagues from the Arthritis Research UK Epidemiology Unit also sought to measure the effect of biologics on ischemic stroke, another risk that weighs especially heavily on RA patients. This confounding factor was eliminated by comparing patients taking anti-TNF drugs to patients taking DMARDs (disease-modifying antirheumatic drugs). Previous studies have been all over the map on this question, finding anywhere from a 60% increase to a 30% reduction in ischemic stroke risk from anti-TNF drugs. This large, well-designed prospective study found no significant effect either way.2

Researchers from St. Vincent's University Hospital in Dublin found that inpatient days and musculoskeletal surgical procedures in RA patients declined in step with increased use of TNF inhibitors between 2000 and 2010. Annual prescriptions rose from 2389 to 116,747 during this period, while the number of major musculoskeletal surgeries fell by 47% — enough to more than offset the cost of the drugs. Other factors may have played a role in improved outcomes, conceded study author Dr Oliver FitzGerald, including more rheumatologists, shorter wait times and better methotrexate use, but "the data are nonetheless compelling; the advent of the biologic era has improved health-related outcomes in patients with RA."3

The most dramatic findings on the safety of biologics came from Canada, where a population-based study of 4312 RA patients using Health Canada data found that use of biologics was associated with a sharply reduced risk of early death. Dr Diane Lacaille of the Arthritis Research Centre of Canada in Vancouver said the effect was consistent across all biologic therapies, not just anti-TNF drugs. The reduction in early death was significant, a hazard ratio of just 0.26, though Dr Lacaille was quick to note that “it wouldn’t be accurate from an epidemiological point of view to say that biologics lead to a 75% reduction” in the risk of premature death.4

The next wave

With impeccable timing, the US FDA approved tofacitinib (Xeljanz) just four days before the conference got underway. Offering both a novel mechanism (JAK3 inhibition) and oral dosing, much is expected of this drug, the first new DMARD in a decade. For now, tofacitinib is approved for patients with poor response to methotrexate, but the ACR conference heard that it also helps patients who have failed to benefit from biologic treatment and even from two biologics. "Low disease activity, as measured by the disease activity score, was reached in about 40% of these difficult-to-treat patients," said lead investigator Dr Gerd Burmester from Berlin's Charité University Hospital. "This is remarkable from a clinical standpoint."5

As has become usual, the outpouring of new knowledge on rheumatoid arthritis was accompanied by mostly awkward silence on RA's poor cousin osteoarthritis, the disease that nobody seems to really understand. But there were a few rays of hope. The investigational agent odanacatib appears effective at improving BMD in women refractory to long-term alendronate. It was also generally well tolerated, reported Dr Roland Chapurlat from Hôpital Edouard Herriot in Lyon, France.6

Dr Chapurlat also participated in the large European SEKOIA trial, which found strontium ranelate effective both at preserving joint structure and controlling symptoms in knee osteoarthritis. This drug has been approved for years in Europe, but seems to get no love from North American regulators. There are sound theoretical reasons — as there were with anti-TNF drugs — for approaching strontium ranelate with caution. But the European data seem to show a mild side-effect profile.7

Conferees look for the window

The debate over early aggressive treatment in RA is over, and early treatment has won. But the question remains: how early? When is the window of treatment where early RA can really be stopped in its tracks? A presentation by New York-based Canadian rheumatologist Dr Vivian Bykerk left little doubt that the earlier, the better, and don't wait too long before starting combination therapy. She pointed to research published last year showing that four in five patients treated with methotrexate and etanercept within four months of diagnosis showed no radiographic progression at one year.8 Future studies must start earlier in the disease course, she urged, "so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?"

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