Faculty Bibliography

Treat-to-target as a strategy for rheumatoid arthritis (RA) is now widely advocated based on strong evidence. Nonetheless, implementation of treat-to-target raises caveats, as is the case with all clinical care strategies. The target of remission or even low disease activity does not apply to all individual patients, some of whom are affected by concomitant fibromyalgia, other comorbidities, joint damage, and/or who simply prefer to maintain current status and avoid risks of more aggressive therapies. No single universal 'target' measure or index exists for all individual RA patients. An emphasis in most studies on radiographic progression, rather than physical function or mortality, as the most important outcome to document the value of treat-to-target may be inappropriate. Many reports imply that the only limitation to treating all RA patients with biological agents involves costs, ignoring effective results in most patients with methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs) and adverse events associated with biological agents. Indeed, the best outcomes in reported RA clinical trials result from tight control with DMARDs, rather than from biological agents, as does better overall status of RA patients at this time compared to previous decades. Pharmacoeconomic reports may ignore that RA patients are older, less educated, and have more comorbidities than the general population, as well as critical differences in patient status according to the gross domestic product of different countries. While treating to a target of remission or low disease activity, including with biological agents, is appropriate for many patients, awareness of these concerns could improve implementation of treat-to-target for optimal care of all RA patients.

Current approach to rheumatoid arthritis (RA) treatment combines early and aggressive therapy, with methotrexate as the anchor medication and monitoring disease activity to achieve the best possible outcome for patients. To recognise which patients are responding treatment and reaching low disease activity levels or remission, an objective outcome measure needs to be utilised in routine clinical care. DAS28, SDAI, CDAI and RAPID3 are all validated and similarly functioning measures that can be of use in everyday care, allowing rheumatologists to treat-to-target. The main challenge remains getting all rheumatologists to start using one of these measures as part of the care they provide.

OBJECTIVES: To determine the preferred treatment for patients with Behcet's syndrome. METHODS: A questionnaire was given to all participants of the 2010 meeting of the International Society for Behcet's Disease. RESULTS: Forty-one respondents from 6 different subspecialties. In the case of a patient with (severe) posterior uveitis or parenchymal central nervous system (CNS) disease no consensus was seen. A diffuse spectrum of different schedules were given. In both uveitis and CNS disease the majority of respondents preferred treatment options consisting of combination systemic therapy and systemic corticosteroids. TNF was preferred as first line drug in uveitis in 7.5% and in severe uveitis in 32.5% of respondents. In parenchymal CNS disease TNF blockage was given by 17% of the respondents. EULAR guidelines regarding uveitis were followed by 12/40 physicians. In patients with a new deep vein thrombosis, 90% of respondents would intensify immunosuppression. More than half would also anticoagulate. CONCLUSIONS: Although consensus about how to treat patients with Behcet syndrome in different clinical situations is far from present, treatment has become more intensive when compared to 10-20 years ago. More uniformity should be sought for in the decision process in individual patients with Behcet's syndrome, regarding their treatment, as well as adhering to evidence, as presented in the EULAR guidelines, when present.

ABSTRACT: In the absence of head-to-head trials, analysis of available data from randomized clinical trials allows for comparison of the efficacy of biologic agents for the treatment of rheumatoid arthritis. Methotrexate (MTX) inadequate responder trials provide data suggesting no major differences among any of the biologic agents, which is also confirmed in MTX naive population trials, when available, possibly a more reliable comparison group. The decision to pick one over the other should focus on safety, long-term survival of the drug and ease of use, which is for the most part influenced by patient preferences.

OBJECTIVE: To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed. METHODS: The rapid onset and systemic efficacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups. RESULTS: The primary efficacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were significantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Significant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were consistent with the known tocilizumab safety profile; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively. CONCLUSIONS: This study demonstrated the efficacy of tocilizumab in improving measures of disease activity in patients with RA who failed to respond adequately to DMARD therapy. Rapid improvement in clinical outcomes was demonstrated in a substudy as early as week 1 as shown by DAS28 scores, patient measures and C-reactive protein. Trial Registry no NCT00531817

ABSTRACT: OBJECTIVE: Behcet's is an idiopathic multi-organ syndrome, which may have onset during childhood. Vascular involvement is uncommon, with rarely reported coronary aneurysm formation. We present a case report of a teenager girl who developed recalcitrant life-threatening Behcet's vasculitis, involving both small and large venous and arterial systems including a giant coronary aneurysm. CASE REPORT: De-identified data were collected retrospectively in case report format. Although our sixteen year old female with Behcet's vasculitis had resolution of many arterial aneurysms, she had persistent venous thrombosis of large vessels, as well as persistent, giant arterial aneurysms requiring intra-arterial coiling of a lumbar artery and coronary bypass grafting despite intensive immunosuppression including glucocorticoids, cyclophosphamide, infliximab, methotrexate, azathioprine and intravenous immunoglobulin. CONCLUSIONS: Vascular manifestations may be seen in Behcet's syndrome, including asymptomatic coronary aneurysm, which may be refractory to immunosuppression and ultimately require surgical intervention. Increased awareness is essential for prompt diagnosis and management.