Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events.

BACKGROUND: Spontaneous reporting systems for adverse drug reactions (ADRs) are handicapped by under-reporting and limited detail on individual cases. We report an investigation from a local surveillance for serious adverse drug reactions associated with disease modifying anti-rheumatic drugs that was triggered by the occurrence of liver failure in two of our patients. METHODS: Serious ADR reports have been solicited from local clinicians by regular postcards over the past seven years. Patients', who had hepatotoxicity on sulfasalazine and met a definition of a serious ADR, were identified. Two clinicians reviewed structured case reports and assessed causality by consensus and by using a causality assessment instrument. The likely frequency of hepatotoxicity with sulfasalazine was estimated by making a series of conservative assumptions. RESULTS: Ten cases were identified: eight occurred during surveillance. Eight patients were hospitalised, two in hepatic failure - one died after a liver transplant. All but one event occurred within 6 weeks of treatment. Seven patients had a skin rash, three eosinophilia and one interstitial nephritis. Five patients were of Black British of African or Caribbean descent. Liver enzymes showed a hepatocellular pattern in four cases and a mixed pattern in six. Drug-related hepatotoxicity was judged probable or highly probable in 8 patients. The likely frequency of serious hepatotoxicity with sulfasalazine was estimated at 0.4% of treated patients. CONCLUSION: Serious hepatotoxicity associated with sulfasalazine appears to be under-appreciated and intensive monitoring and vigilance in the first 6 weeks of treatment is especially important.

Benchmarking the nurse consultant role in rheumatology.

This article demonstrates how the four core standards for the nurse consultant role have been developed and applied in the field of rheumatology. The authors suggest that the standards: expert practice, leadership and service redesign, research and education, are relevant for consultant nurses in all specialties. The standards can be used by other nurse consultants to benchmark their practice.

Monitoring and assessing the safety of disease-modifying antirheumatic drugs: a West Midlands experience.

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.

Providing patients with information about disease-modifying anti-rheumatic drugs: Individually or in groups? A pilot randomized controlled trial comparing adherence and satisfaction.

BACKGROUND: Communicating information about disease-modifying anti-rheumatic drugs (DMARDs) before patients start treatment is a key role for some rheumatology clinical nurse specialists. This is done in our unit to promote understanding of the risks and benefits of drug therapy and encourage timely and reliable use of DMARDs. Information is routinely provided individually but this can lead to delays in starting treatment because of limited nursing resources. In this randomized trial we tested the feasibility of giving patients, who were about to start on a DMARD, information about the drug in groups and compared this with information given individually. METHODS: Adults with a clinical diagnosis of rheumatoid arthritis or psoriatic arthritis who were referred to the nursing team for counselling about starting on methotrexate, sulfasalazine or leflunomide were included. Patients who had previously taken a DMARD were not excluded and those consenting were randomized to receive drug information individually or in groups (of three to six patients). We provided all patients with written materials about the relevant drug and discussed the risks and benefits of drug use verbally. Patients allocated to group counselling received this intervention in a teaching room, with a slide presentation. The primary outcome was adherence with medication use, ascertained by pill counts, self-report diaries and prescription dispensation. Secondary outcomes included satisfaction with information about medicines (SIMS) by questionnaire; time taken to provide information; adherence to scheduled hospital appointments and blood monitoring schedules; and DMARD continuation rates at four and twelve months. RESULTS: Of 127 eligible patients referred for counselling about DMARDs, 62 consented to take part: 32 were randomized to receive drug information individually and 30 to receiving it in groups. Patients allocated to the two different interventions were comparable for age and diagnoses at baseline but more patients allocated individual counselling had not taken a DMARD previously: 56% (18/32) versus 20% (6/30). More patients counselled in groups were adherent (27/30; 90%) compared with patients counselled individually (22/32; 69%; p = 0.06) by pill counts. However, on self-report diaries, similar proportions were adherent (group counselling 97% (29/30) versus individual 94% (30/32); p = 1.0). All but two prescriptions were dispensed. More patients allocated to individual counselling missed at least one blood monitoring visit (25% versus 17%; p = 0.54) and at least one scheduled clinic visit (19% versus 3%; p = 0.10). SIMS scores indicated high levels of patient satisfaction and were similar for both groups. The time taken to run group and individual counselling sessions were similar (median of 35 minutes versus 33 minutes, respectively). Nursing time per individual patient in those allocated group counselling was 11.6 minutes. Drug continuation rates were higher for those counselled in groups compared with those counselled individually: at four months, 73% versus 63 %; p = 0.42; at twelve months, 47% versus 38%; p = 0.61). CONCLUSIONS: Our pilot study demonstrated the feasibility of providing counselling on DMARDs to groups of patients with important time savings for specialist nurses and while maintaining high levels of patient satisfaction. There was a trend for better outcomes in terms of adherence and drug continuation rates for patients counselled in groups, indicating potential benefits from group interactions. However, these findings need to be investigated further in a larger, fully powered trial.

Patient self-injection of methotrexate for inflammatory arthritis: a study evaluating the introduction of a new type of syringe and exploring patients' sense of empowerment.

OBJECTIVES: To evaluate the introduction of a new type of syringe for patients on a self-injection of methotrexate (MTX) programme and explore patients' sense of empowerment relating to the self-injection of MTX. METHODS: Data were collected using a postal questionnaire, which yielded quantitative and qualitative data. The questionnaire was sent to all eligible patients in the primary care setting who self-injected MTX (n=24). RESULTS: The response rate was 88% (n=21). Patients' responses illustrated numerous disadvantages of using the syringe, particularly difficulties with the syringe stopper, syringe handling and leakage potential of the mildly cytotoxic drug MTX. The advantages included the ease of syringe storage and longer use by date. Difficulties in using the syringe, and the amount of support and training from hospital staff were among the factors affecting patients' sense of empowerment. CONCLUSIONS: Although a small study, this work indicates that there may be benefits in a collaboration between hospital staff and the syringe manufacturer, to modify the new syringe to address the problems noted. The potential of cytotoxic MTX spillage being minimized is recognized, making the new syringe more suitable for use by patients with inflammatory arthritis. Patient training may help to alleviate difficulties in using a new syringe, which, in turn, may also increase patients' sense of empowerment.

A study of parenteral use of methotrexate in rheumatic conditions.

1. This paper reports the findings of a small pragmatic study to compare the safety and efficacy of methotrexate administered by intramuscular and subcutaneous injection, and to teach patients to self-administer methotrexate by the subcutaneous route. 2. Eight patients with rheumatic conditions, already receiving a stable weekly dose of methotrexate by intramuscular injection, were entered into this 13-week study. 3. Serum levels of methotrexate were measured on six consecutive occasions: three whilst patients received intramuscular methotrexate and then three after switching to the subcutaneous route. 4. Patients were taught to self-administer their methotrexate subcutaneously and were then discharged to perform this task at home. 5. Levels of disease activity and psychological scores were measured at the start and end of the study. Satisfaction with self-administration and teaching of injection techniques were assessed at 13 weeks. 6. Serum methotrexate levels were not significantly affected by the route of administration. All patients were able to perform self-injection safely and seven out of eight preferred self-administration at home. 7. This small study demonstrates that there is no difference in the safety and efficacy of methotrexate given by either parenteral route. Patients were able to administer safely methotrexate subcutaneously. Self-administration reduced hospital visits, was more convenient for patients and improved patient satisfaction.