Abstract
Background: Serious adverse events may occur from the use of disease modifying antirheumatic drugs (DMARDs) used to treat rheumatoid arthritis. We describe preliminary data from a regional surveillance scheme. Our aims were to identify a broad range of potential adverse events, to identify deficiencies in care and examine the management of common events in order to improve care.
Methods: Adverse events were sought by regular postcards to clinicians in the West Midlands region of the UK. Each reported case was carefully described and the opinions of at least three peer-reviewers were sought on cause-effect relationships, the potential for prevention and the appropriateness of management.
Results: Forty-four serious adverse events associated with DMARD use were reported between December 1999 and October 2001. Events included eight patients with malignancies, two with pancytopenia taking methotrexate, three with septic arthritis, and two with septicaemias. Fifteen cases have been peer-reviewed in detail, so far. At least two reviewers thought that eight events were related to DMARD use and that two were preventable. Agreement between pairs of reviewers was fair or moderate (weighted kappa 0.23–0.5).
Discussion: We have successfully implemented a regional system for identifying potential drug-related serious adverse events. A diverse range of potential drug-related events has been seen. Early analyses have highlighted the difficulties of determining cause-effect relationships between a drug and an event.
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References
Scottish Intercollegiate Guidelines Network (SIGN). Management of early rheumatoid arthritis [online]. Available from URL: http://www.sign.ac.uk [Accessed 2001 Feb 25]
Jobanputra P, Hunter M, Clark D, et al. An audit of methotrexate and folic acid for rheumatoid arthritis: experience from a teaching centre. Br J Rheumatol 1995; 34: 971–5
American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis Rheum 2002; 46: 328–46
Comer M, Scott DL, Doyle DV, et al. Are slow-acting antirheumatic drugs monitored too often? An audit of current clinical practice. Br J Rheumatol 1995; 34: 966–70
Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. JAMA 1995; 274: 29–34
Andrew LB, Stocking C, Krizek T, et al. An alternative strategy for studying adverse events in medical care. Lancet 1997; 349: 309–13
Hayward RA, Hofer TP. Estimating hospital deaths due to medical errors: preventability is in the eye of the reviewer. JAMA 2001; 286: 415–20
Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 356: 1255–9
Jobanputra P, Homer D. Adverse drug reactions [letter]. Lancet 2001; 357: 561
Gruchalla RS. Clinical assessment of drug-induced disease. Lancet 2000; 356: 1505–11
Figueiras A, Tato F, Fontaiñas J, et al. Influence of physicians attitudes on reporting adverse drug events: a case-control study. Med Care 1999; 37: 809–14
Eland IA, Belton KJ, van Grootheest AC, et al. Attitudinal survey of voluntary reporting of adverse drug reactions. Br J Clin Pharmacol 1999; 48: 623–7
Brewer T, Colditz GA. Postmarketing surveillance and adverse drug reactions: current perspectives and future needs. JAMA 1999; 281: 824–9
Callum KG, Gray AJG, Hoile RW, et al. Extremes of age. The 1999 report of the National Confidential Enquiry into Perioperative Deaths [online]. Available from URL: http://www.ncepod.org.uk/99intro.pdf [Accessed 2002 Oct 7]
US Food and Drug Administration. Guideline for industry: clinical safety data management: definitions and standards for expedited reporting [online]. Available from URL: http://www.fda.gov/medwatch/report/iche2a.pdf [Accessed 2001 Nov 27]
Medicines Control Agency. The yellow card scheme: the updated yellow card [online]. Available from URL: http://www.mca.gov/ [Accessed 2001 Nov 27]
US Food and Drug Administration. MedWatch: the FDA safety information and adverse event reporting program [online]. Available from URL: http://www.fda.gov/medwatch/getforms.htm [Accessed 2001 Nov 27]
Armitage P, Berry G. Statistical methods in medical research. 3rd ed. Oxford: Blackwell Science Ltd, 1994
Li Wan Po A, Kendall MJ. Causality assessment of adverse events. Drug Saf 2001; 24: 793–9
Hutchinson TA, Flegel KM, HoPingKong H, et al. Reasons for disagreement in the standardized assessment of suspected adverse drug reactions. Clin Pharm Ther 1983; 34: 421–6
Goldman RL. The reliability of peer assessments of quality of care. JAMA 1992; 267: 958–60
Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239–45
Leape LL, Bates DW, Cullen DJ, et al. Systems analysis of adverse drugs events. JAMA 1995; 274: 35–43
Acknowledgements
This report is presented on behalf of Rheumatology Units from six National Health Service (NHS) Hospital Trusts. All of the rheumatologists shown below have either contributed cases or peer reviewed cases. We acknowledge their help and the help of secretarial staff at their NHS institutions. Drs David Carruthers, Caroline Gordon, Christopher Buckley, and Deva Situnayake, at City Hospital NHS Trust, Birmingham; Drs George Kitas, Andrew Whallett, John Delamere, Guest Hospital, Dudley; Drs Ian Rowe and Ashok Rai, Worcestershire Royal Infirmary NHS Trust; Drs Simon Bowman, Mark Pugh, and Nuton Faisal, Heartlands Hospital NHS Trust; Drs Diarmuid Mulherin and Tom Sheeran, Cannock Hospital NHS Trust; Drs Ronald Jubb, Elizabeth Rankin, Bijoya Roychaudury and Jonathan Packham, Selly Oak Hospital, University Hospital Birmingham NHS Trust.
No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.
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Jobanputra, P., Maggs, F., Homer, D. et al. Monitoring and Assessing the Safety of Disease-Modifying Antirheumatic Drugs. Drug-Safety 25, 1099–1105 (2002). https://doi.org/10.2165/00002018-200225150-00004
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DOI: https://doi.org/10.2165/00002018-200225150-00004