Paresh Jobanputra

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

BackgroundSpontaneous 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.MethodsSerious 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.ResultsTen 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.ConclusionSerious hepatotoxicity associated with sulfasalazine appears to be under-appreciated and intensive monitoring and vigilance in the first 6 weeks of treatment is especially important.

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

BACKGROUNDnCommunicating 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.nnnMETHODSnAdults 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.nnnRESULTSnOf 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).nnnCONCLUSIONSnOur 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.

A randomised efficacy and discontinuation study of etanercept versus adalimumab (RED SEA) for rheumatoid arthritis: a pragmatic, unblinded, non-inferiority study of first TNF inhibitor use: outcomes over 2 years

Objective To compare adalimumab versus etanercept in patients with active rheumatoid arthritis (RA) to test the hypothesis that adalimumab was not inferior to etanercept in terms of drug continuation by a margin of 15% after 52u2005weeks of treatment. Design Pragmatic, randomised, parallel group, multicentre, unblinded and non-inferiority trial. Randomisation stratified by baseline use of methotrexate. Participants 125 adults with active RA despite treatment with two disease-modifying drugs (DMARDs), including methotrexate randomised (1u2009:u20091) to adalimumab 40u2005mg alternate weeks or etanercept 50u2005mg weekly, added to existing medication. Measurements The primary outcome was proportion of patients continuing treatment after 52u2005weeks. Secondary outcomes included: disease activity score using 28 joints (DAS28), treatment satisfaction (TSQM V.2), health status (Euroqol-5D), drug toxicity and persistence with therapy after 2u2005years. Results Persistence with therapy was 65% for adalimumab versus 56.7% for etanercept (one-sided 95% CI for proportion still taking adalimumab minus proportion on etanercept ≥−7.9%); demonstrating non-inferiority at the 15% margin. After 2u2005years these figures were: adalimumab 58.3% and etanecept 43.3% (CI ≥−1.7%). The proportion of good, moderate and non-responders based on DAS28-C reactive protein, after 52u2005weeks, were 26.3%, 33.3% and 40.4%, respectively, for adalimumab versus 16.7%, 31.7% and 51.7%, respectively, for etanercept (p=0.158). Baseline median EQ-5D scores improved from 0.52 to 0.69 for adalimumab and from 0.52 to 0.64 for etanercept (p=0.046) after 52u2005weeks. Global satisfaction, effectiveness, side effects and convenience scores based on the TSQM were similar for both drugs. Fourteen serious adverse events occurred including two deaths from myocardial infarction, one patient with ovarian cancer and one with acute myeloid leukaemia. Conclusions Clinicians choosing a first tumour necrosis factor inhibitor for active RA, despite trying two DMARDs including methotrexate, may choose either adalimumab or etanercept in the knowledge that these drugs are similarly effective. Clinical trial registration number EU Clinical Trials Register 2006-006275-21/GB.

Patterns of analgesic use, pain and self-efficacy: a cross-sectional study of patients attending a hospital rheumatology clinic

BackgroundMany people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors.MethodsConsecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as I always take my tablets every day. Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests.Results218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain.Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003).ConclusionOur study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain.

A clinician’s critique of rheumatoid arthritis health economic models

Modelling cost-effectiveness of new drugs for RA has become increasingly prevalent and sophisticated. This situation has arisen largely because regulatory agencies, such as the National Institute for Health and Clinical Excellence, have demanded models from industry and have commissioned independent models. Many technical aspects of health economic models have converged-yet the results of models differ greatly. These differences can be accounted for in large part by differences in assumptions about the nature of patients likely to be treated; likely treatment sequences; likely responses to treatment; likely continuation on drug and likely disease progression, in particular. Such parameters cannot be fixed and evolve with changing practice and are ideally captured by contemporary data. Importantly, data from the local setting to which a health economic problem is applied are necessary, but in the absence of ideal sources, for the many contributions needed, considerable differences in opinion and biases are commonplace. In the final analysis, all models are just that, models, and as such an approximation of real life. Thus, although considerable heat is generated during debates about model parameters, model outputs may just yield sufficient light for regulatory agencies allocating resources.