Leflunomide in Takayasu arteritis – A long term observational study

Souza, Alexandre Wagner Silva de; Agustinelli, Renan de Almeida; Almeida, Hemerli de Cinque; Oliveira, Patrícia Bermudes; Pinheiro, Frederico Augusto Gurgel; Oliveira, Ana Cecília Diniz; Sato, Emília Inoue

doi:10.1016/j.rbre.2016.02.003

Cited by 32 publications

(33 citation statements)

References 13 publications

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“…In contrast to the positive trends observed in GCA, the RCT of abatacept did not show any signs of efficacy in TAK 67. Lower quality evidence from uncontrolled prospective and retrospective case series exists for the use of conventional immunosuppressive agents such as MTX, leflunomide, mycophenolate mofetil, azathioprine and cyclophosphamide in TAK 112–117. Since TAK targets primarily women with childbearing potential and is a chronic and usually not acutely life threatening disease (unlike AAV), the use of cyclophosphamide should be limited to patients where other treatments have failed or are not tolerated.…”

Section: Resultsmentioning

confidence: 91%

2018 Update of the EULAR recommendations for the management of large vessel vasculitis

et al. 2019

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BackgroundSince the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.MethodsUsing EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.ResultsThree overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40–60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.ConclusionsWe have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.

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Section: Resultsmentioning

confidence: 91%

2018 Update of the EULAR recommendations for the management of large vessel vasculitis

et al. 2019

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“…Leflunomide that has been shown to be effective and safe not only in rheumatoid arthritis, but also in systemic vasculitides, e.g. granulomatosis with polyangiitis and Takayasu arteritis, was never formally studied in GCA [11][12][13][14]. It has shown promise in two case series of relapsing or persistently active GCA or polymyalgia rheumatica [15,16].…”

Section: Introductionmentioning

confidence: 99%

Does leflunomide have a role in giant cell arteritis? An open-label study

et al. 2018

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Glucocorticoid monotherapy has been the mainstay treatment of giant cell arteritis (GCA) for decades. We aimed to evaluate the role of leflunomide as a steroid-sparing agent in GCA. This open-label study included incipient GCA patients followed for at least 48 weeks at a single secondary/tertiary rheumatology centre. At the time of diagnosis, patients received glucocorticoids. At week 12 of follow-up, leflunomide 10 mg qd was recommended as an adjunctive therapy to all patients without contraindications. The decision to start the leflunomide was patient-dependent. The number of relapses, a cumulative glucocorticoid dose during follow-up and treatment-related adverse events (AE) were recorded and compared between glucocorticoid-only and leflunomide groups. Seventy-six patients (65.8% female, median (IQR) age 73.7 (66.1-78.8) years) were followed for a median (IQR) 96 (86-96) weeks. Thirty out of 76 (39.5%) patients received leflunomide at week 12 (leflunomide group); the others continued treatment with glucocorticoid (glucocorticoid-only group). During the first 48 weeks of follow-up, 22 patients relapsed, 4 (13.3%) in leflunomide group and 18 (39.1%) in glucocorticoid-only group. The difference was statistically significant (p = 0.02; NNT 3.9 (95% CI 2.2-17.4)). Furthermore, 17/30 (56.7%) patients in the leflunomide group managed to stop glucocorticoid at week 48 (with one relapse (5.9%) shortly afterwards). The cumulative glucocorticoid dose at the last visit was lower in the leflunomide group than in the glucocorticoid-only group (p = 0.01). Our findings indicate the steroid-sparing effect of leflunomide in GCA.

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“…Use of leflunomide in 15 patients with refractory TA from Brazil resulted in clinical response in 12/15 with significant reduction in GC dose over 9 months . In a longer‐term follow up of these patients (mean 43 months), those who continued to be on leflunomide ( n = 5) had similar clinical response and angiographic progression at the end of the observation period when compared to those who had to change to another immunosuppressive therapy for persistent disease activity ( n = 7) . Oral or monthly intravenous cyclophosphamide use in adult patients with TA has been described in retrospective case series from Europe for 14 patients with TA with follow‐up period ranging 10–45 months, with favorable clinical responses in all and resolution of vascular wall inflammation by PET‐CT (in three out of four patients) .…”

Section: Conventional Dmardsmentioning

confidence: 99%

Recent advances in the management of Takayasu arteritis

et al. 2019

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Takayasu arteritis (TA) is a challenging large vessel vasculitis to treat. Distinguishing disease activity from vascular damage is difficult, often relying on clinician judgement aided by composite clinical disease activity indices with angiographic evidence of vessel wall thickening or vessel wall hypermetabolism demonstrable on positron emission tomography computerized tomography (PET CT). Glucocorticoids form the mainstay of remission induction. While other conventional disease modifying anti-rheumatic drugs (cDMARDs) or biologic DMARDs (bDMARDs) are commonly used, evidence supporting their usefulness is sparse and generally of low quality. The only two randomized controlled trials (RCT) of a DMARD in TA failed to show efficacy of abatacept in reducing relapses of TA, however, tocilizumab showed a trend towards reduction in time to relapses. Of the cDMARDs, methotrexate, azathioprine, mycophenolate mofetil (MMF), leflunomide and cyclophosphamide have shown clinical efficacy in case series, with some evidence that methotrexate, azathioprine and MMF might retard angiographic progression. Among bDMARDs, anti-tumor necrosis factor alpha agents and tocilizumab may be useful in patients refractory to cDMARDs with retardation of angiographic progression, based on evidence derived from mostly retrospective case series, whereas the role of rituximab and ustekinumab needs further elucidation. Revascularization, either surgical or endovascular, is the treatment of choice to relieve critical, symptomatic stenoses and are best undertaken during inactive disease. Emerging evidence suggests that patients with TA also have increased cardiovascular risk and this requires appropriate management. Large studies involving multiple centers are the need of the hour to appropriately evaluate utility of currently available immunosuppressive therapy in TA.

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Leflunomide in Takayasu arteritis – A long term observational study

Abstract: Leflunomide led to sustained remission in approximately half of patients at a mean time of 12 months and was well tolerated by TA patients.

Cited by 32 publications

References 13 publications

2018 Update of the EULAR recommendations for the management of large vessel vasculitis

2018 Update of the EULAR recommendations for the management of large vessel vasculitis

Does leflunomide have a role in giant cell arteritis? An open-label study

Recent advances in the management of Takayasu arteritis

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