Rheumatoid Arthritis: Kiely P

Maddison P, Kiely P, Kirkham B, Lawson T, Moots R, Proudfoot D, Reece R, Scott D, Sword R, Taggart A, Thwaites C, Williams E. · Department of Rheumatology, Ysbyty Gwynedd Hospital, University of Wales, Bangor LL57 2PW, UK. · Rheumatology (Oxford). · Pubmed #15657072 links to  free full text

Abstract: OBJECTIVES: To determine, by consensus, the optimal use of leflunomide in rheumatoid arthritis (RA), using a multidisciplinary panel of experts and performing meta-analyses of available data. METHODS: A multidisciplinary panel of experts in RA was convened. Important questions, pertinent to the use of leflunomide in the treatment of RA, were defined by consensus at an initial meeting. Each question was allocated to subgroups of two or three members, who worked separately to prepare a balanced opinion, based on published literature, data from individual patients taking part in phase II and phase III clinical trials provided by Aventis, and data from a USA-based medical claims database (AETNA). The full group then reconvened to agree on an overall consensus statement. Recommendations concerning efficacy and tolerability versus comparator drugs and placebo were derived from two new meta-analyses. RESULTS: Leflunomide was at least as effective as sulphasalazine and methotrexate, and equally well tolerated on meta-analysis of trial data. Overall withdrawal rates for all adverse events were similar for all three drugs. Avoidance of the loading dose reduces 'nuisance' side-effects (e.g. nausea), but probably delays the onset of action. Adverse events could usually be managed by dose reduction and/or symptomatic therapy. CONCLUSIONS: On the basis of efficacy, safety and cost, leflunomide should be considered in patients with RA who have failed first-line DMARD drug therapy. In refractory cases, leflunomide may be used in combination with, for example, methotrexate before biological agents. Therapy should be initiated by a specialist, but repeat prescribing in general practice on a shared care basis is acceptable using agreed protocols. Clear mechanisms are required to monitor toxicity, with good communication between the patient and rheumatologist to manage nuisance side-effects and avoid unnecessary discontinuation of leflunomide.

Kiely P, Williams R, Walsh D, Young A, Anonymous00023. · Department of Rheumatology, St George's Healthcare NHS Trust, London, UK. · Rheumatology (Oxford). · Pubmed #18984608 No free full text.

Abstract: OBJECTIVES: To report from the Early Rheumatoid Arthritis Network (ERAN), time from symptom onset to start of therapy, treatment choices and disease outcome in early RA. METHODS: Patients with newly diagnosed RA were prospectively enrolled from 19 centres in the UK and Eire. Standardized information was collected on case report forms at first presentation, 3-6 months, 1 yr and annually thereafter. The choice and intensity of drug treatment was left to the discretion of individual centres. RESULTS: A total of 808 patients were recruited between 2002 and 2007, with a mean follow-up of 16 (0-60) months. Of them, 62% fulfilled four or more ACR criteria for RA at first visit. The median time from onset of symptoms to referral to secondary care was 4 months [interquartile range (IQR) 2-9, n = 655] and to start of first DMARD 8 months (IQR 4-13, n = 638). DMARDs were prescribed in 97% of the patients, initially as monotherapy in 91%, and as combination therapy in 9%. The second DMARD (n = 220) was a switch to another as monotherapy in 52% and step-up to combination therapy in 48%. The proportions with a 28-joint disease activity score >5.1 at baseline and 3 yrs were 46 and 19%, >3.2 were 84 and 54% and <2.6 were 6 and 33%, respectively. CONCLUSIONS: Patients presenting with RA in ERAN do not receive DMARDs promptly, largely due to delays in referral to secondary care. Contemporary treatment practice is to start with DMARD monotherapy, and to use combination DMARDs as second-line therapy in approximately half of them. Over 3 yrs the proportion of patients continuing to have active disease remains high.