Tocilizumab in patients with Takayasu arteritis: a retrospective study and literature review.

OBJECTIVES: To assess the efficacy of tocilizumab (TCZ) in patients with Takayasu arteritis (TA). METHODS: Multicentre open-label retrospective study. RESULTS: Eight patients (all women) with a mean age of 34±16 years, median 36 years (range: 7-57) were assessed. The main clinical features at TCZ therapy onset were: constitutional symptoms (n=4), fever (n=3), headache (n=2), chest pain (n=1), abdominal pain (n=1), mesenteric ischaemia (n=1), myalgia involving the lower limbs (n=1), cerebral vascular insufficiency (n=1), malaise (n=1), upper limb claudication (n=1) and nodular scleritis (n=1). Besides corticosteroids and before TCZ treatment onset, 7 of 8 patients had also received several conventional immunosuppressive and/or biologic agents. Seven patients experienced marked clinical improvement in the first 3 months after the onset of TCZ therapy. After a median follow-up of 15.5 [interquartile range-IQR: 12-24] months, 7 patients were asymptomatic. The median C-reactive protein decreased from 3.09 [IQR: 0.5-12] to 0.15 [IQR: 0.1-0.5] mg/dL (p=0.018), and median erythrocyte sedimentation rate from 40 [IQ range: 28-72] to 3 [IQR: 2-5] mm/1st hour (p=0.012). The median dose of prednisone was also tapered from 42.5 [IQR: 25-50] to 2.5 [IQR: 0-7.5] mg/day (p=0.011). However, TCZ had to be discontinued in 1 patient because she developed a systemic lupus erythematosus, and in another patient due to inefficiency. TCZ dose was reduced in a patient because of mild thrombocytopenia. CONCLUSIONS: TCZ appears to be effective in the management of patients with TA, in particular in patients refractory to corticosteroids and/or conventional immunosuppressive drugs.

Tocilizumab in refractory aortitis: study on 16 patients and literature review.

OBJECTIVES: Non-infectious aortitis is often refractory to standard immunosuppressive therapy. Since IL-6 has been implicated in the pathogenesis of aortitis, we assessed the efficacy of the anti-IL6 receptor monoconal antibody tocilizumab (TCZ) in a series of patients with refractory non-infectious aortitis. METHODS: Review of 16 patients (14 women/2 men) with refractory aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that were treated with TCZ. RESULTS: The mean age±SD was 51.4±20.1 years. The underlying conditions were: Takayasu arteritis (TakA) (n=7 cases), giant cell arteritis (GCA) (n=7), relapsing polychondritis (RP) (n=1), and aortitis associated with retroperitoneal fibrosis (n=1). TCZ was the first biologic drug used in all patients with GCA and in the patient with aortitis associated with retroperitoneal fibrosis but in only 2 of 7 TakA patients. In the remaining cases anti-TNF inhibitors were prescribed before TCZ (standard dose was 8 mg/kg/iv/4 weeks). After a mean±SD follow-up of 11.8±6.6 months most patients experienced clinical improvement, showing reduction of erythrocyte sedimentation rate from 43±36 mm/1st h to 5±4 mm/1st h at last visit. At TCZ onset, 25% of patients had fever and 19% polymyalgia rheumatica. These manifestations disappeared after 3 months of TCZ therapy. A corticosteroid sparing effect was also achieved (from 27.3±17.6 mg/day of prednisone at TCZ onset to 4.2±3.8 mg/day at last visit). TCZ had to be discontinued in a patient because of severe neutropenia. CONCLUSIONS: TCZ appears to be effective and relatively safe in patients with inflammatory aortitis refractory to corticosteroids or to other biologic immunosuppressive drugs.

Double positivity for rheumatoid factor and anti-CCP autoantibodies: improving referral from primary care of patients suspected of having rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic progressive autoimmune inflammatory disease with significant morbidity and mortality. The course of the disease can be modified if diagnosis is early and treatment appropriate. AIM: In this study, we aimed to evaluate a new strategy for early identification of RA patients in primary care settings (the 'diagnostic bottleneck') based on serological biomarkers and to manage inappropriate rheumatoid factor (RF) laboratory test requests. METHOD: A two-arm study was carried out. The first arm corresponded to a retrospective observational descriptive study of patients referred for RF testing from primary care using the current laboratory workflow. The second arm included the following prospective interventions: cancelation of RF requests corresponding to patients with previous negative results for RF over a one-year period; and automatic reflex testing antibodies against cyclic citrullinated proteins (anti-CCP) for patients displaying RF values >30 IU/ml. Outcomes from both arms were then compared. FINDINGS: As double positivity for RF and anti-CCP notably increases the positive likelihood ratio of RA. The intervention enabled a reduction of 2813 tests in 22 months. Moreover, the frequency of unnecessary referrals was reduced from 22% to 8.2%, while that of missed patients decreased slightly (from 21% to 16%), with the number of patients diagnosed per RF request remaining unchanged. In terms of costs, we saved 19.4 RF tests per anti-CCP test added.We developed a simple and cost-effective strategy for reducing the time to diagnosis of RA that can improve patients' quality of life. This approach was supported by primary and specialised care.

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review.

OBJECTIVE: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. METHODS: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. RESULTS: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. CONCLUSION: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.

Strategy to improve the request of uric acid in primary care: preliminary results and evaluation through process and outcome appropriateness indicators.

INTRODUCTION: Alerted by the high rates of request of serum uric acid (UA) in primary care patients, we aimed to design a strategy to improve such an indicator, and to monitor such an intervention through process and outcome appropriateness indicators. METHODS: To design the strategy, several meetings were held between the Laboratory, Rheumatology and Primary Care. The intervention consisted of discharging UA from two laboratory profiles ("Health Check" and "Rheumatology"), making it only possible to request the test in an individualized manner. To assess the intervention effectiveness, the ratio of UA/glucose requests, the quantity of allopurinol prescription and the resulting economic savings were calculated and compared for pre- and post-intervention 12 month periods. RESULTS: There was a 70% decrease in the number of UA requests in the post-intervention period, as compared to the pre-intervention interval. The ratio of UA/glucose requests experienced a significant commensurate drop in the post-intervention period (p<0.01). There was a significant reduction in the prescription of allopurinol (p<0.01). From an economic perspective, the strategy resulted in a savings of 8190 €. CONCLUSION: The strategy resulted in a dramatic drop in the number of UA requests and in the prescription of allopurinol. This highlights a likely existence of prior unnecessary treatment of patients with hyperuricemia in the absence of clinical symptoms.