Rheumatology最新文献

Objectives: The primary objective was the safety of subcutaneous immunoglobulin, IgPro20 (Hizentra, CSL Behring) in adults with diffuse cutaneous systemic sclerosis (dcSSc). Secondary objectives included pharmacokinetics and relative bioavailability of IgPro20, and safety and pharmacokinetics of intravenous immunoglobulin, IgPro10 (Privigen, CSL Behring).

Methods: In this prospective, multicentre, randomised, open-label, crossover Phase 2 study (NCT04137224), patients (aged ≥18 years) with dcSSc were assigned to 16 weeks of IgPro20 (0.5 g/kg/week) followed by 16 weeks of IgPro10 (2 g/kg/4 weeks over 2-5 sessions), or vice-versa. Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infusion site reactions (ISRs), clinical tests, pharmacokinetic and bioavailability were assessed.

Results: Twenty-seven patients were randomised from 9 October 2019-31 August 2021. In total, 22 patients (81.5%) experienced 107 TEAEs (IgPro20, 49; IgPro10, 58); most were mild/moderate. Six patients (22.2%) experienced ten SAEs (IgPro20, 6; IgPro10, 4); no treatment-related SAEs and no deaths were reported. IgPro20 ISR rate was low (2 per 100 infusions). Maximum immunoglobulin G concentration (mean [standard deviation]) was numerically lower following IgPro20 (23.7 [1.2] g/l) vs IgPro10 (46.1 [1.2] g/l), as was the geometric mean dose-normalised, baseline-corrected area under the concentration-time curve from time point 0 to tau (IgPro20, 44.8 [1.4] h*g/l; IgPro10, 60.2 [1.4] h*g/l). The bioavailability of IgPro20 relative to IgPro10 was 76.1%.

Conclusion: This study shows that in patients with dcSSc, safety, pharmacokinetic and bioavailability profiles of IgPro20, and safety and pharmacokinetics of IgPro10, are similar to those observed in other approved indications.

Trial registration: https://clinicaltrials.gov, NCT04137224.

Objectives: Although with great advances, the biomarkers used in the diagnosis of rheumatoid arthritis (RA) are still challenging, especially in seronegative RA. Recently, procollagen C-endopeptidase enhancer (PCOLCE) was revealed as a potential autoantigen of seronegative RA by our group. This study aimed to further analyze the B cell autoantigenic epitopes of PCOLCE and the diagnostic value of its antibody in seronegative RA.

Methods: The B cell epitopes of PCOLCE were elucidated by the Immune Epitope Database and molecular mimicry analyses. The anti-citrullinated PCOLCE271-284 antibody (anti-PCOLCE) was tested in a total of 612 serum samples including RA patients, healthy controls, and patients with other rheumatic diseases. The diagnostic value of anti-PCOLCE in RA, especially for seronegative RA, was evaluated by ROC curve, sensitivity, and specificity. Anti-PCOLCE in combination with anti-CCP for RA diagnosis was also demonstrated. The correlations of anti-PCOLCE with RA patient features were further analyzed.

Results: Anti-PCOLCE was significantly elevated in RA serums with a sensitivity of 51.53% and specificity of 93.60%. More importantly, anti-PCOLCE had a favorable diagnostic value in seronegative RA, revealing a positive rate of 40.00% in anti-CCP negative RA, 38.76% in RF negative RA, and 36.46% in anti-CCP and RF negative RA. The combination of anti-PCOLCE with anti-CCP demonstrated a high sensitivity of 82.14% and specificity of 90.21%. Anti-PCOLCE also has good diagnostic value in RA patients with normal inflammatory factors and early RA. Moreover, anti-PCOLCE was positively correlated with CRP, anti-CCP, and RF.

Conclusion: Anti-PCOLCE could serve as a novel biomarker for RA, especially for seronegative RA.

Objectives: To confirm the presence of different disease phenotypes of pediatric SAPHO syndrome (pSAPHO) based on their skin manifestations in a large cohort of Italian patients.

Methods: pSAPHO were enrolled in the Eurofever Registry and the data retrospectively analysed. Patients were divided depending on their skin manifestations into an Acne-Hidradenitis suppurativa (HS) group and a Palmoplantar Pustulosis-Psoriasis Vulgaris (PPP-PV) group and were compared with patients without skin manifestations (chronic non-bacterial osteomyelitis, CNO). Comparison of frequencies between groups was performed by the means of χ2 test or by Fischer's Exact test.

Results: 54 pSAPHO with skin manifestations (35 acne-HS, 19 PPP-PV) were enrolled and compared with 167 CRMO. In the Acne-HS, 82.9% were males, in the PPP-PV, 84.2% were females, while in the CNO group there were no gender differences (p< 0.0001). The 3 groups differed significantly for age at disease onset: acne-HS median 13.3 years, PPP-PV median 10.2 years, CNO median 9.5 years (p= 0.0001). An axial pattern was more frequent in acne-HS (91.4%) and PPP-PV group (89.4%) compared with CNO (46%) (p< 0.0001). Both acne-HS (82.9%), and PPP-PV (63.2%) required more frequently a biologic therapy than CNO (36.8%), but acne-HS presented a refractory skin disease requiring steroids and different lines of treatment, while PPP-PV responded well to biologics.

Conclusions: Our data have identified two different phenotypes of pSAPHO based on skin manifestations, with different sex, age and response to treatments. These two groups have peculiar clinical features different from the CNO group. A new classification encompassing these phenotypes is warranted.