The effectiveness of biological agents, e.g. tumour necrosis factor antagonists, for treating inflammatory arthritis is well established. However, the risk of adverse effects has not been well defined. It is known that treatment with biological agents is associated with serious infections, lymphoma and tuberculosis (TB) reactivation. A systematic review and network meta-analysis published in the Cochrane Library
has attempted to estimate the risk of adverse events during treatment with this class of drugs across a range of indications (excluding human immunodeficiency disease – HIV/AIDS). 1
The reviewers identified 163 randomised controlled trials (RCTs) and 46 extension studies yielding a total of 61,964 patients. The duration of the studies was short – median 6 months for RCTs and 13 months for extension studies. First the good news: the rates of serious adverse events, serious infections, lymphoma and congestive heart failure were not statistically significantly different between biological agents and placebo. And now for the bad news: as a group, in the short term, biological agents were associated with significantly higher rates of total adverse events, withdrawals from studies due to adverse events, and TB reactivation compared with placebo. Some agents were associated with increased specific adverse outcomes but the numbers of adverse events were small and there was no consistency across the outcomes, so it was difficult to draw firm conclusions from these results. Further studies are clearly needed to assess long-term outcomes of treatment with biological agents.
Cardiovascular effects of non-steroidal anti-inflammatory agents
Another network meta-analysis
has tried to provide answers to the question, ‘Which non-steroidal anti-inflammatory drug (NSAID) is safest for patients with cardiovascular risk factors?’ This is important as so many patients with musculoskeletal pain are elderly and have significant cardiac risk. The reviewers identified 31 trials yielding over 115,000 patient-years of follow-up. They used the data to calculate the risk profiles of 7 different NSAIDs and COX-2s. Outcomes were myocardial infarction (MI), stroke and death from cardiovascular disease (CVD). The study found that rofecoxib was associated with the highest rate of MI and ibuprofen with the highest risk of stroke. Etoricoxib and diclofenac were associated with the highest rates of death from CVD. Naproxen seemed to be the least harmful but the authors cautioned that none of these drugs could really be considered safe in CVD. 2