Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GCA. Tocilizumab (TCZ), a humanised antihuman IL-6 receptor antibody, has been used successfully in several reports as a treatment for GCA and LVV. We report the potentially long-term successful use of TCZ in 8 cases of refractory LVV. All of our patients achieved a good clinical response to TCZ and C reactive protein reduced from an average of 70.3 to 2.5. In all cases, the glucocorticoid dose was reduced, from an average of 24.6 mg prednisolone prior to TCZ treatment to 4.7 mg, indicating that TCZ may enable a reduction in glucocorticoid-associated adverse events. However, regular TCZ administration was needed for disease control in most cases. TCZ was discontinued in one case due to the development of an empyema indicating the need for careful monitoring of infection when using this treatment.
Giant cell arteritis (GCA) is a large-vessel vasculitis predominantly affecting older people, with a peak incidence between 70 and 79 years of age. If untreated, ischaemic complications can be catastrophic for the patient, including blindness. We review the current treatment paradigms for this condition, the mainstay of which is immediate high-dose glucocorticoid therapy with a gradual dose tapering. Adverse events of glucocorticoid therapy are often observed after 12-24 months and corticosteroid-sparing adjuvant therapies are used in severe disease, multiple flares or patients at high risk of prolonged therapy. The current understanding of the pathogenesis of GCA is explored. This has informed the identification of new potential targets and approaches to treatment. Blockade of interleukin (IL)-6 (tocilizumab) and IL-1 (gevokizumab) are being evaluated in phase III clinical trials. It is hoped that improved risk stratification of organ damage and relapses will be developed using imaging and biomarkers, allowing for individualised treatment for patients; however, there remains further work to be done before this becomes a reality.
BackgroundTumour Necrosis Factor (TNF) inhibitors are routinely used in managing rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). In 2012 and 2015, the patents for the Etanercept (ETN) and Infliximab (IFX) originator molecules expired in Europe respectively and the use of biosimilar ETN and IFX was approved for use in England.ObjectivesTo determine the proportion of rheumatology patients who experienced a flare of their disease following a switch from originator to biosimilar IFX or ETN and in those who flared, to determine whether disease control can be re-captured following reverting to the originator product.MethodsThis was a retrospective study of all patients switched from their originator IFX or ETN to their corresponding biosimilar product between July 2016 and July 2017 at a UK tertiary rheumatology centre. A total of 475 patients were identified by our Biologics team. Seventeen patients experienced a flare defined by: an increase in Disease Activity Score (DAS)28>1.2 points in RA, worsening of any of the Psoriatic Arthritis Response Criteria (PsARC) in PsA, an increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of at least 1 unit in SpA, and worsening of swollen and tender joint count in our patient with adulthood juvenile idiopathic arthritis (JIA). Follow-up at 3 months determined disease re-capture, defined by an improvement in DAS28 score >1.2 units, improvement in at least two of the PsARC, one to be tender or swollen joint score, an improvement of BASDAI score and improved swollen and tender joint count in our patient with adulthood JIA.ResultsDiagnosisFlareRe-capture of disease control following switch back to originatorSide effects INFLIXIMABRA4/63 (6.3%)1/4 (25.0%)1/63 (1.6%)PsA2/15 (13.3%)0/20SpA2/19 (10.5%)1/2 (50.0%)1/19 (5.3%)JIA1/1 (100%)1/1 (100%)0ETANERCEPTRA4/238 (1.7%)4/4 (100%)6/238 (2.5%)PsA1/55 (1.8%)1/1 (100%)2/55 (3.6%)SpA3/84 (3.6%)2/3 (66.7%)2/84 (2.4%)Nine patients (9.2%) who switched to biosimilar IFX flared: four with RA, two with PsA, two with SpA and one with JIA. Of those, three patients (33.3%) were able to re-capture disease control on switching back to originator IFX. Two patients (2.0%) experienced side effects on switching to biosimilar IFX.Eight patients (2.1%) experienced a flare on switching to biosimilar ETN: four with RA, one with PsA and three with SpA. Of those, seven patients (87.5%) re-captured disease control on switching back to originator ETN. Ten patients (2.7%) experienced side effects on switching to biosimilar ETN.ConclusionsThe majority of our patients did well following the switch to biosimilar IFX and ETN.Patients who did flare on biosimilar ETN are more likely to re-capture their disease control than those who flared on biosimilar IFX.This adds to real-world evidence to support the European League Against Rheumatism recommendations to utilise biosimilar therapy in rheumatology practice, which is likely to include patients who differ from those enrolled in clinical trials; important when considering...
Clinicians, patients, and others have shown considerable interest in the subject of tumor necrosis factor inhibitor (TNFi) dose tapering in ankylosing spondylitis (AS) because of the drug's high cost and potential for toxicity 1,2,3 . In the ANSWERS (ANkylosing Spondylitis With Etanercept RegimeS) trial, we demonstrated that over 50% of participants originally treated with etanercept (ETN) 50 mg once weekly (OW) who were then randomized to a tapered dose of ETN 25 mg OW maintained the primary outcome measure [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) reduction by ≥ 50% or ≥ 2 points, and a ≥ 2-unit reduction in spinal pain measured on a 10-point visual analog scale] at the 6-month followup 4 .All patients enrolled in the initial study gave their written consent. / eudract-web/index.faces, EudraCT number: 2010-029013-10). We have now followed this cohort prospectively to determine whether the "tapered" patients in the ETN 25 mg OW arm could successfully maintain the primary outcome measure in longterm followup. In patients who failed to maintain this response, full-dose ETN 50 mg OW was reinstated.Twelve patients were included within the ETN 25 mg OW group; 75% men, mean age 52 years, median BASDAI 2.8 [interquartile range (IQR) 2.0]. After a mean followup period of 50 months, 4 patients (33%) continued treatment with ETN 25 mg. One patient discontinued ETN because of side effects and has not been receiving biologic therapy. The remaining 7 patients experienced a flare of disease after a mean of 16 months and were reinstated with ETN 50 mg OW; 5 reattained low disease activity and 2 were switched and responded to an alternative TNFi.Twenty-one patients continued treatment with ETN 50 mg: 95% men, mean age 60 years, median BASDAI 1.9 (IQR 1.6). Fourteen patients (67%) continued treatment with ETN 50 mg, 3 were lost to followup, 2 developed inflammatory bowel disease and switched to adalimumab (ADA), 1 flared at 15 months and switched to ADA, and another discontinued ETN because of mood disturbance and has not continued biologic therapy.
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