Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Risk of Cancer in RA Patients Treated with Disease-Modifying Drugs

Source: Lopez-Olivo MA, et al. Risk of malignancies in patients with rheumatoid arthritis treated with biologic therapy: A meta-analysis. JAMA 2012;308:898-908.

IN THE EARLY YEARS OF TREATMENT EXPERIence with biologic response modifiers (BRMs) for rheumatoid arthritis (RA), concern was raised that the immune-modulating effects responsible for dramatic symptomatic improvement might also lead to increased risk for cancer. Indeed, based on excess cases of lymphoma reported in the Adverse Event Reporting System database among children and adolescents treated with BRMs, the FDA recommended a warning label for all TNF-inhibitors. Should we be worried about cancer risk in patients treated with BRMs?

Lopez-Olivo et al performed a data analysis on randomized, controlled trials (n = 63 trials) of BRM treatment in RA patients in which a BRM was compared with placebo or another traditional therapy such as methotrexate (n = 29,423). A wide variety of BRMs was included in the analysis (e.g., abatacept, adalimumab, anakinra).

This dataset was restricted to trials with at least 6 months’ duration. No signal for increased risk of cancer was discerned. Although a trend for increased risk of lymphoma was found, the numbers did not achieve statistical significance. It is not possible to determine whether longer-term outcomes in relation to BRMs will be impacted by cancer risk, since this dataset is comprised of studies of 3 years’ duration or less. Additionally, whether RA patients who have already suffered a cancer are at greater risk of recurrence subsequent to BRM treatment is unknown. The dramatic RA disease remission we have come to commonly see thanks to treatment with BRMs appears to be safe from an increased risk for cancer.


A Different Kind of Fish Story

Source: Rizos EC, et al. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: A systematic review and meta-analysis. JAMA 2012;308:1024-1033.

THE IDEA THAT OMEGA-3 POLYUNSATUrated fatty acids — a.k.a. fish oil — are beneficial stems from some positive randomized clinical trials. But the word “some” is limiting in the previous sentence, since some other trials do not report benefit. Rizos et al performed a systematic review and meta-analysis based on 28 studies (n = 68,680) in which adults were treated with omega-3 fatty acids for primary or secondary prevention of cardiovascular disease.

Studies were reported between 1999-2010, and averaged 2 years of follow-up, although some data went as long as 6.2 years. The majority of trials were secondary prevention trials, which — because they represent a higher risk group — might be anticipated to more readily demonstrate risk reduction.

Contrary to popular opinion, this meta-analysis was unable to confirm any positive effects of omega-3 fatty acids, whether the metric was all-cause mortality, cardiac death, sudden death, MI, or stroke. Most of the trials used combinations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), leaving open the possibility that an EPA or DHA individually might have produced different results. The authors conclude that their data support neither the routine inclusion of omega-3 fatty acids in clinical practice nor guideline recommendations that advocate their use.


Antidepressants and Auto Accidents

Source: Orriols L, et al. Risk of injurious road traffic crash after prescription of antidepressants. J Clin Psychiatry 2012;73:1088-1094.

DRIVING SIMULATION TESTS PERFORMED with healthy, non-depressed volunteers indicate varying degrees of deleterious effect on driving skills with tricyclics (TCA) and mirtazapine, but less so with selective serotonin reuptake inhibitors (SSRIs) and venlafaxine. In direct contrast, but perhaps more pertinent to clinical medicine, trials of driving performance in depressed patients on antidepressants suggest better driving skills on SSRIs or mirtazapine than TCAs or venlafaxine. To gain more insight into the effects of antidepressant treatments on auto crashes, Orriols et al reviewed the database of accidents accrued by the French police force from 2005-2008 (n = 210,818).

Being on an antidepressant increased the odds ratio of being the at-fault driver by 34% compared with persons not on antidepressants. The immediate time period around initiation or change of treatment was particularly high risk. Subgroup analysis found the greatest risk among persons receiving serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine) and the least risk among TCA recipients (e.g., amitriptyline). Even though driving simulation tests suggest that depressed patients who are being treated perform better than untreated patients, clinicians must still exercise vigilance and should consider informing patients — especially upon initiation of or change in treatment — about driving risks.