Patient safety is a big deal; and getting bigger. The last fifteen years have seen incredible improvements in the ability to treat a number of rheumatic diseases. These improvements have been due to the introduction of biologic therapies into common use throughout the world. Each of these biologic therapies works by blocking a specific receptor or eliminating a specific type of cell related to the immunologic function, or actually, at least in part, dysfunction in patients with a rheumatic disease. However, this specificity is deceptive as each of these receptors or cell types was chosen based on basic science research showing the relationship of the specific target of the biologic therapy to a broad network of inflammatory mechanisms. Our understanding of the impact of these biologic therapies, both good and bad, is incomplete but the focus of intense research. The depth of this research effort is supported by the submission of over 50 manuscripts for review for this safety-themed issue. The breadth of the research effort is demonstrated by the scope of approaches included in this issue — from investigation of drug-induced DNA damage and repair in individual cells to very large international population-based efforts to describe rates of very rare adverse events.
This drug safety–themed issue of Arthritis Care & Research is part of a large and multifaceted effort of the American College of Rheumatology (ACR) to provide timely, accurate, and comprehensive information related to treatment safety to those taking care of individuals with rheumatic diseases. This is a large and ongoing challenge. In a survey of a random sample of ACR members and all the nurses and physician assistant members of the Association of Rheumatology Health Professionals performed in 2008, 85% indicated that they were either “concerned” or “very concerned” about drug safety issues. However, only 12% of those responding felt “very well” informed about drug safety issues. This is in part an inevitable outcome of the relatively recent and ongoing introduction of a large number of unique treatment options for rheumatic and other inflammatory diseases. It is also a reflection on the incomplete information we currently have about these therapies. The articles included in this issue of Arthritis Care & Research provide much information that will be helpful in better understanding these complex issues.
The articles in this issue provide many perspectives on patient safety. Two articles provide information relevant to many different types of therapies. Hudson and Suissa used published studies to demonstrate several types of biases seen in observational studies, the effects of the biases on the results of the studies, and ways to avoid or minimize the effects of biases in future observational studies; and Nestoriuc et al showed that the attitude of patients prior to initiation of new therapies (i.e., those with negative attitudes about medications) was far more predictive of the occurrence of side effects than disease severity or medication-specific characteristics. This study by Nestoriuc and colleagues suggested that identifying and addressing patient concerns about medications prior to initiation of new therapies may be helpful in decreasing the occurrence of adverse events.
Several articles address the safety of anti–tumor necrosis factor (anti-TNF) agents. Caporali et al demonstrated that anti-TNF therapy did not seem to have any adverse effect on the hepatic status in individuals that had previously been infected with hepatitis B. They did not detect any evidence of reactivation of hepatitis B virus replication in patients receiving anti-TNF therapy. Hastings et al demonstrated that neutropenia was not uncommon in those receiving anti-TNF therapy and some of the individuals demonstrated serious infections due to neutropenia. In a novel case report, Racunica et al discussed the possibility that the reconstitution of the immune system after stopping anti-TNF therapy is associated with the development of new autoimmune disease manifestations. Dixon et al use data from a large British registry to address the safety of the use of anti-TNF therapies in rheumatoid arthritis patients who have had a prior malignancy. Their study provided reassuring but not definitive evidence that treatment of those with a prior malignancy was not associated with an increased risk of incident malignancy.
Several articles address issues of drug safety in children. In a prospective, interventional study, Lahdenne et al demonstrated that the use of pretreatment with acetaminophen and cetirizine (an antihistamine) did not decrease or prevent the frequency of infusion reactions to infliximab therapy. Smith et al described the work of a broad-based constituency to develop on an international basis a consolidated longitudinal registry of patients with juvenile idiopathic arthritis undergoing routine clinical care to provide a more robust assessment of current and new therapies in children. The development of such a consolidated registry was stimulated by a recent meeting organized by the Food and Drug Administration in May 2009, and work is ongoing at this time.
In the study by Wolfe and Marmor, the risk for developing retinal toxicity from one of the oldest rheumatic treatments, hydroxycholoroquine, was studied in almost 4,000 patients with rheumatoid arthritis or systemic lupus erythematosus. Retinal toxicity was found to be uncommon, especially in the first 5 to 7 years of therapy, but occurs in approximately 1% of those who remain on the therapy for longer than 5 years. The authors recommend that new screening guidelines be developed for those receiving hydroxychloroquine.
This issue of Arthritis Care & Research provides a wide variety of approaches and useful information on the safety of treatments in both adults and children with rheumatic diseases. In addition, new areas of research are suggested.