British Society For Rheumatology Guidelines Research Articles

Discussion of the 2007 British Society for Rheumatology guidelines for management of ANCA-associated vasculitis

Discussion of the 2007 British Society for Rheumatology guidelines for management of ANCA-associated vasculitis

Real life experience confirms sustained response to long-term biologics and switching in ankylosing spondylitis

To investigate the long-term response to biological therapies in AS in a real life clinical setting and to quantify non-response and response to 'switching' therapies in these cases. All patients prescribed TNF-blocking therapies for AS between 1999 and 2006 were studied. Response was evaluated using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and CRP results. A total of 113 patients (84 males: 29 females, mean age 45 yrs, median disease duration 16 yrs, 87% HLA-B27 positive) were identified. At baseline they had a mean BASDAI of 6.57, BASFI 6.57 and CRP of 31 g/dl. At the end of follow-up, these values had reduced to mean BASDAI of 3.12, BASFI 4.16 and CRP of 7 g/dl. Improvements were sustained for 24 months and beyond with no loss of effect. Only nine patients (8%) suffered side-effects leading to cessation or switching of first-line therapy and non-response occurred in 15 patients (13%) in the long term. Fifteen patients (13%) switched to a second drug and 14 of these (93%) had a significant and sustained response. Outcomes were similar regardless of drug used, duration of disease and HLA-B27 status. Treatment of active AS with TNF blockers according to the British Society of Rheumatology guidelines leads to a sustained response for over 2 yrs with most patients tolerating the drugs well. The rate of non-response is significantly lower than that seen in RA and nearly all of these patients respond well to a second-line agent.

Disseminated tuberculosis after anti-TNFα treatment

A 74-year-old white woman with rheumatoid arthritis since 1993 presented to us in September, 2005, with a 2-month history of progressive shortness of breath, fatigue, and dry cough which had worsened over the preceding 3 weeks, with no associated fever, night sweats, or weight loss. Her medical history included ischaemic heart disease, hypertension, chronic renal impairment, and diabetes mellitus. She was taking meloxicam, aspirin, gliclazide, rosuvastatin, lansoprazole, furosemide, insulin, prednisolone (10 mg/day), and adalimumab. She had tried various disease modifying drugs, including hydroxychloroquine, sulfasalazine, methotrexate (15 mg/week for over a year) and lefl unomide (20 mg/day) for her arthritis; all had to be stopped because of side-eff ects or ineffi cacy. In October, 2003, her disease activity score (DAS) was 9·3 (25 swollen joints, 28 tender joints, ESR 106 mm/h, visual analogue scale [VAS] 100). She was assessed according to the British Society for Rheumatology guidelines to receive anti-TNFα therapy. She had no history of tuberculosis, although her sister did. The screening chest radiograph was normal and tuberculin skin test was negative. She was started on adalimumab in November, 2003, but did not receive concomitant methotrexate because it had been stopped previously owing to shortness of breath. Her arthritis responded well with a DAS of 3·52 in March, 2004 (1 swollen joint, 5 tender joints, ESR 17 mm/h, VAS 0). On admission, she was apyrexial, blood pressure 131/53 mm Hg, pulse 97 beats per min, respiratory rate 20 breaths per min, and oxygen saturation 96% on air. She had a right-sided pleural eff usion confi rmed on chest radiograph. Full blood count, urea and electrolytes, and liver function were normal. Pleural fl uid for acid-fast bacilli, tuberculosis culture and PCR, and cytology was negative. CT of the thorax and abdomen confi rmed right pleural eff usion, lower lobe collapse, mediastinal lymphadeno pathy, and lung infi ltrates with numerous masses in the liver. While awaiting liver biopsy she deteriorated rapidly and died in October, 2005. Post-mortem examination showed multiple caseating granulomas with Langhan’s-type giant cells in the lungs, liver, lymph nodes (fi gure), and spleen; tissue specimens were negative for acid fast bacilli, and tuberculosis culture and PCR. A postmortem diagnosis of disseminated miliary tuberculosis was made on the basis of histology. There is a fi ve-fold increased risk of tuberculosis associated with anti-TNFα therapy in rheumatoid arthritis. Most cases are due to reactivation of latent tuberculosis and usually occur in the early phase of treatment, although cases have been reported after 2 years. The presentation is often atypical with extra pulmonary or disseminated disease. Our patient presented nearly 2 years into her treatment—her screening tests for tuberculosis before initiation of adalmimuab were negative, although her tuberculin skin test might have been falsely negative due to steroids. Before starting adalimumab, her tuberculosis risk was assessed and it was felt that the risk of tuberculosis prophylaxis outweighed the risk of disease (she had had abnormal liver function tests on lefl unomide). There was considerable diffi culty in arriving at the diagnosis of tuberculosis in our patient because she presented with atypical symptoms and all the microbiological tests to diagnose tuberculosis were negative. Our case highlights three important points. Firstly, current screening tests can miss latent tuberculosis especially in immunosuppressed patients; newer blood tests, which detect γ-interferon, are promising. Secondly, it can be diffi cult to diagnose tuberculosis with PCR and culture; histopathology is important in diagnosing diffi cult cases and should be requested early on, the results of which are available within days. Thirdly, patients on anti-TNFα therapy who present with persistent respiratory symptoms with any suspicion of tuberculosis should be considered for empirical anti-tuberculosis treatment despite the lack of microbiological evidence and while awaiting tissue diagnosis.

Updating the British Society for Rheumatology guidelines for anti-tumour necrosis factor therapy in adult rheumatoid arthritis (again)

Updating the British Society for Rheumatology guidelines for anti-tumour necrosis factor therapy in adult rheumatoid arthritis (again)

The updated BSR guidelines for anti‐TNF in adults with RA: What has changed and why?

In 2001 the British Society for Rheumatology (BSR) published guidelines for prescribing TNF-alphablockers in adults with rheumatoid arthritis (RA). In an unusual move, the National Institute of Clinical Excellence (NICE) accepted the BSR guidelines and published them unchanged and included them in their own Technology Appraisal (National Institute of Clinical Excellence, 2002). The field of anti-TNF in RA is rapidly changing, and the BSR Standards, Guidelines and Audit Working Group decided in 2004 to update the guidelines. These were published in February 2005 (Ledingham and Deighton, 2005). This article summarizes the key changes, and attempts to justify them, using further data that has emerged since the updated guidelines were produced, and audit data from the Derby Rheumatology department.

Update on the British Society for Rheumatology guidelines for prescribing TNF blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001)

These guidelines have been developed for use by prescribing secondary-care rheumatologists. They are intended to indicate which adult patients with rheumatoid arthritis (RA) may benefit from the anti-tumour necrosis factor (anti-TNF) therapies, precautions that need to be taken in their use and to highlight potential side-effects from these therapies. The previous guidelines applied to the then available anti-TNF therapies (etanercept and infliximab) [1]. These current guidelines would apply to these two products together with adalimumab, which is a newly licensed anti-TNF therapy for RA. This is a rapidly changing field with new data emerging each month, so that it is vital that clinicians keep up to date with this area of practice. These guidelines can only incorporate information that was available to the authors at the time of their completion. The guidelines have been drawn up by the above working party and have been approved by the British Society for Rheumatology (BSR) Standards, Guidelines and Audit Working Group (SGAWG). National Institute of Clinical Excellence (NICE) guidelines, Medline literature searches for published data on the anti-TNF drugs and data from the pharmaceutical companies producing anti-TNF agents have been used to draw together the updated guidelines. The guidelines were subject to a consultation process at the BSR Annual Meeting 2004 and feedback was received from BSR members, allied health professionals, patient representatives and members of the pharmaceutical industry. The BSR SGAWG will be responsible for initiating a further update of these guidelines in the future and for auditing their use. The anti-TNF therapies are not necessarily the only treatment option available to patients who are eligible for treatment according to these guidelines—the potential risks versus the benefits need to be considered for each individual case. There will be circumstances in which rheumatologists will feel that there are other drugs that may be equally likely to produce a good clinical response. In the UK all patients commenced on the following anti-TNF therapies need to be registered on the BSR biologics register (BSRBR): etanercept, infliximab, adalimumbab and anakinra. It is currently intended that data be collected on 4000 patients per antiTNF therapy. Thereafter the BSR would recommend continued data collection, in the same format as for the BSRBR, at a local level. These guidelines will be updated as other anti-TNF treatments are included in the register. For further clarification before registration, please contact Dr Kath Watson, BSRBR Study Co-ordinator, arc Epidemiology Unit, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT, UK (Tel: 0161 275 1613, E-mail: biologics.register@ man.ac.uk). Adverse incidents/serious side-effects arising whilst on antiTNF therapy should be notified immediately via the yellow card system, but also to the BSRBR via the 6-monthly review sheets. Rheumatologists have responsibility for supplying updated information to the BSRBR as required and as requested. Written consent will be sought from patients for their participation in this study via the BSRBR.