Treatment of giant cell arteritis with ultra-short glucocorticoids and tocilizumab: the role of imaging in a prospective observational study

Objectives: To assess the impact of tocilizumab (TCZ) monotherapy after ultra-short-pulse glucocorticoids (GCs) on clinical manifestations, and vessel inflammation and damage in large vessel-GCA (LV-GCA). Methods: In this prospective observational study, we enrolled patients with active LV-GCA. All patients received 500 mg per day i.v. methylprednisolone for three consecutive days and weekly s.c. TCZ injections from day 4 until week 52. PET/CT was performed on all patients at baseline and at weeks 24 and 52. The primary end points were the reduction in the PET vascular activity score (PETVAS) at weeks 24 and 52 compared with baseline, and the proportion of patients with relapse-free remission at weeks 24 and 52. The secondary end point was the proportion of patients with new aortic dilation at weeks 24 and 52. Results: A total of 18 patients were included (72% female, mean age 68.5 years). Compared with the baseline value, a significant reduction in the PETVAS was observed at weeks 24 and 52, mean (95% CI) reductions -8.6 (-11.5 to -5.7) and -10.4 (-13.6 to -7.2), P = 0.001 and 0.002, respectively. The proportion of patients with relapse-free remission at weeks 24 and 52 was 10/18 (56%, 95% CI 31-78) and 8/17 (47%, 95% CI 23-72), respectively. At weeks 24 and 52, no patient had shown new aortic dilation. However, 4 patients who had shown aortic dilation at baseline showed a significant increase in aortic diameter (≥5 mm) at week 52. Conclusion: TCZ monotherapy after ultra-short-pulse GCs controlled the clinical symptoms of GCA and reduced vascular inflammation. Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05394909

Identification of the Clinical Features Distinguishing Psoriatic Arthritis and Fibromyalgia

To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM)

PTPN22 R620W polymorphism in the ANCA-associated vasculitides

Objectives. PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism ( SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. Methods. PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. Results. The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, chi(2) = 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, chi(2) = 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, chi(2) = 7.258, OR = 1.98), lung involvement (P = 0.0060, chi(2) = 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, chi(2) = 16.567, OR = 3.73). Conclusion. The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset

Tocilizumab for polymyalgia rheumatica: Report of two cases and review of the literature.

Background: Glucocorticoids (GC) are the mainstay of treatment of polymyalgia rheumatica (PMR). However GC-related adverse events occur frequently, particularly in patients with relapsing disease. Several studies have demonstrated that IL-6 is a key player in the pathogenesis of PMR. Objectives: To report 2 patients with PMR treated with the anti-IL-6 receptor monoclonal antibody tocilizumab (TCZ) and to review the published evidence on the efficacy and safety of TCZ in patients with PMR. Methods: We treated 2 GC-naive patients with newly diagnosed pure PMR with monthly TCZ infusions (8 mg/kg body weight) for 6 months. Disease activity and drug tolerability were assessed clinically, by laboratory tests, and bilateral shoulder ultrasonography before starting the treatment and subsequently every month during TCZ therapy. We performed a systematic literature search (PubMed until July 2012) using the terms "tocilizumab," "anti-IL-6-receptor," "polymyalgia rheumatica," "giant cell arteritis", and "large-vessel vasculitis" to identify published reports of patients with PMR treated with TCZ. Results: One of our patients responded well to TCZ, while the other patient required GC therapy after the 2nd TCZ infusion because of lack of appreciable clinical response. Both patients tolerated TCZ well. The review of the literature revealed 4 reports with a total of 9 patients who received TCZ for PMR. In 7 of these 9 patients, PMR was associated with giant cell arteritis. Including our patients, 5 patients received TCZ alone and 6 TCZ plus GC. A good response to TCZ treatment was observed in all patients reported in the literature without any major adverse events. Conclusions: TCZ both as monotherapy and in association with GC appears to be mostly effective and safe to treat patients with PMR. However, larger controlled studies are required to confirm these favorable data

Tocilizumab: a novel therapy for patients with large-vessel vasculitis

OBJECTIVE: Treatment of large-vessel vasculitis (LVV) remains challenging. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose or after GC withdrawal. In addition, GCs are fraught with numerous adverse events. The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with LVV. METHODS: Four patients with active LVV (two with GCA and two with Takayasu arteritis) received monthly TCZ infusions (8\u2009mg/kg bodyweight) for 6 consecutive months. Two patients were treatment na\uefve, while two had relapsing disease. Disease activity and drug tolerability were assessed clinically and by laboratory tests at study entry and subsequently every month for 6 months of TCZ treatment, while an [(18)F]fluorodeoxyglucose PET (PET/CT) scan was performed before and after treatment. In addition, a semi-quantitative clinical evaluation was performed at baseline and at 3 and 6 months using the Indian Takayasu activity score and the Kerr indices. After TCZ, MTX was used as maintenance therapy. RESULTS: All patients treated with TCZ therapy had a satisfactory clinical and laboratory response, while PET/CT findings significantly improved in all cases. No serious adverse events were noted. Only one patient had a transient increase in liver enzymes. CONCLUSIONS: In this small group of patients with LVV, treatment with TCZ was effective and well tolerated. Further, larger studies are required to confirm our findings

The codon 72 polymorphic variants of p53 in Italian rheumatoid arthritis patients

The p53 tumor suppressor protein plays an important role in cell apoptosis. The wild type p53 protein presents a common polymorphism at position 72 resulting in either a proline or an arginine residue at this position, leading to differences between the two variants in the induction of apoptosis. We examined the possible associations of this polymorphism with the occurrence of rheumatoid arthritis (RA) and its severity in a series of RA patients of Italian origin

Tocilizumab in glucocorticoid-naive large-vessel vasculitis.

Glucocorticoids (GC) are the mainstay of treatment of large-vessel vasculitis (LVV), but a sizeable number of patients relapse upon tapering the GC dose or after discontinuation of GC therapy. In addition, GC cause numerous adverse events. Therefore, in patients with longstanding disease and in those at risk for GC-related adverse events, the use of alternative therapeutic agents should be considered. Interleukin-6 (IL-6) is a key player in the pathogenesis of LVV. Preliminary data suggest the efficacy of the IL-6 receptor inhibitor tocilizumab (TCZ) in patients with LVV. We report 2 treatment-na\uefve patients with a recent diagnosis of LVV who received monthly TCZ infusions (8 mg/kg body weight) for 6 consecutive months as monotherapy because of relative contraindications and patients' reluctance to take GC. In both cases we observed a complete clinical response and normalisation of inflammatory markers as well as a decrease in vascular FDG uptake and SUV ratio on fluorodeoxyglucose positron emission/computerised tomography. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels rose in both patients after TCZ therapy. TCZ may be an effective alternative to GC treatment for LVV patients at risk for GC-related adverse events. Larger studies are required to confirm our findings

Tocilizumab in glucocorticoid-naïve large-vessel vasculitis

Glucocorticoids (GC) are the mainstay of treatment of large-vessel vasculitis (LVV), but a sizeable number of patients relapse upon tapering the GC dose or after discontinuation of GC therapy. In addition, GC cause numerous adverse events. Therefore, in patients with longstanding disease and in those at risk for GC-related adverse events, the use of alternative therapeutic agents should be considered. Interleukin-6 (IL-6) is a key player in the pathogenesis of LVV. Preliminary data suggest the efficacy of the IL-6 receptor inhibitor tocilizumab (TCZ) in patients with LVV. We report 2 treatment-naïve patients with a recent diagnosis of LVV who received monthly TCZ infusions (8 mg/kg body weight) for 6 consecutive months as monotherapy because of relative contraindications and patients' reluctance to take GC. In both cases we observed a complete clinical response and normalisation of inflammatory markers as well as a decrease in vascular FDG uptake and SUV ratio on fluorodeoxyglucose positron emission/computerised tomography. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels rose in both patients after TCZ therapy. TCZ may be an effective alternative to GC treatment for LVV patients at risk for GC-related adverse events. Larger studies are required to confirm our findings