When rheumatology meets hepatology: are anti-TNFs safe in hepatitis B virus carriers?

Over the past decades, more effective and less toxic biologicals have revolutionized rheumatology therapy in our battle against the autoimmune chronic inflammation of rheumatoid arthritis and spondyloarthropathy. But what about for patients who have previously had an infection of the liver? Prior hepatitis B virus infection clearly presents a challenge for clinicians. In a study by Charpin and colleagues of 21 patients whose hepatitis B virus serology suggested carrier status, anti-TNF treatment appeared to be safe during a limited follow-up period of 3 years. Studies are needed with longer follow-up, particularly in patients with low antibody titres (antiHBc). In the 3-year period, however, about 30% of the patients developed significant lowering of antibody titres, which may become relevant during long-term follow-up. Charpin and colleagues are the first to reveal promising data on the relative safety of anti-TNFs in a small series of hepatitis B carriers for up to 3 years

Management of hyperuricemia in gout: focus on febuxostat

Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than “standard dosage” allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol

The Prevalence of Titanium Dioxide Particles in Synovial Fluid Samples Drops after European Union Ban

Due to health concerns, the European Union has banned the use of titanium dioxide nanoparticles in consumables in February 2022, with a 6-month transitional period ending in August 2022. We studied the prevalence of titanium dioxide nanoparticles in synovial fluid samples during and after the transitional period. A total of 302 samples were collected as a consecutive series between 1 April 2022 and 15 June 2023 from patients visiting the department of rheumatology at VieCuri Medical Centre in Venlo, The Netherlands. The samples were primarily collected for diagnostic purposes and only clinical waste material was used for this study. From each sample, up to 40 μl of fluid was analysed with Raman spectroscopy for the presence of titanium dioxide particles. The trend in prevalence was calculated with a 3-month wide moving average. A total of 13 out of 302 samples (4.3%) contained titanium dioxide (TiO2). The prevalence of TiO2 decreased between the transitional period and the period after the ban (p = 0.0154, with a relative risk ratio of 4.9 (95% CI 1.35–17.74). There was no significant difference in patient characteristics between the TiO2 positive and the TiO2 negative group. These results are hinting towards a possible relationship between the EU-ban and the identified decrease in prevalence

Real-life results of urate-driven pharmacotherapy with three urate lowering drugs in gout:allopurinol, febuxostat and benzbromarone

Aim:This study aims to assess outcomes of gout patients from the treat to target (T2T) perspective at 6 months and 12 months while using urate lowering therapy (ULT): allopurinol, febuxostat, and/or benzbromarone.Methods:All gout patients visiting the Rheumatology department between 2015 to 2021 were identified from the digital hospital system. The diagnosis of gout was based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2015 classification criteria. Patient outcomes were predefined intention to treat (ITT) categories: category 1: patients with serum uric acid (sUA) ≤ 0.360 mmol/L (ACR target for gout); category 2: patients with sUA ≤ 0.300 mmol/L (ACR/EULAR target for severe gout); category 3: patients with sUA > 0.360 (failure to meet ACR target).Results:Gout diagnoses were present in 1,186 patients: 986 (83.1%) males and 200 (16.9%) females. A follow-visit at 6 months was present in 76.9% (n = 856) out of 1,113 patients reaching sUA < 0.36 mmol/L, but 257 (23%) failed to reach the 0.36 mmol/L target. At 12 months, a follow-up visit was available in 792 (71.1%) patients, and from these, 710 (90%) had reached sUA < 0.36 mmol/L target. The use of benzbromarone was a strong predictor of reaching the sUA < 0.30 mmol/L target: odds ratio (OR) 3.2, 95% confidence interval (CI) (1.735, 6.017) at 6 months. Diabetic patients had the highest proportion of not reaching the target: 18%. Male patients needed higher dosages of allopurinol to reach the sUA target at 6 months compared to female patients.Conclusions:This is a large study on a T2T approach based in a real-life clinical setting. Only 42% reached the sUA target at 6 months with allopurinol 300 mg quaque die (QD) monotherapy. About 77% of gout patients reach the predefined sUA target of 0.36 mmol/L at 6 months with the availability of three ULTs. There is still a significant unmet need in gout as many patients failed to achieve predefined sUA targets

Diagnostic Accuracy of Raman Spectroscopy Integrated With Polarized Light Microscopy for Calcium Pyrophosphate–Associated Arthritis

Objective: We studied the performance of integrated Raman polarized light microscopy (iRPolM) for the identification of calcium pyrophosphate (CPP)–associated arthritis (CPPD). Methods: This is a diagnostic accuracy study including 400 consecutive synovial fluid samples from a single hospital in the Netherlands. Accuracy measures were calculated against polarized light microscopy (PLM) and the 2023 American College of Rheumatology (ACR)/EULAR criteria set for CPPD. Results: The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (κ = 0.88). The diagnostic performance of iRPolM compared to the 2023 ACR/EULAR criteria set was sensitivity 86.0% (95% confidence interval [CI] 73.3–94.2), specificity 99.1% (95% CI 97.5–99.8), positive likelihood ratio 100.33 (95% CI 32.3–311.3), negative likelihood ratio 0.14 (95% CI 0.07–0.28), positive predictive value 93.5% (95% CI 82.2–97.8), negative predictive value 98.0% (95% CI 82.2–97.8), and accuracy 97.5% (95% CI 95.5–98.8). We allowed rheumatologists to rate the certainty of their microscopic identification of CPP and found a large correspondence between iRPolM and a certain identification (κ = 0.87), whereas only 10% of the uncertain CPP identifications could be confirmed with iRPolM. We identified several novel particle types in synovial fluid analysis, including calcium carbonate crystals, deposited carotenoids, microplastics, and three types of Maltese cross birefringent objects. Conclusion: iRPolM can easily identify CPP crystals with a strong diagnostic performance. PLM alone is not specific enough to reliably resolve complicated cases, and the implementation of Raman spectroscopy in rheumatology practice can be of benefit to patients with suspected CPPD.</p

Association of gestational thyroid function and thyroid peroxidase antibody positivity with postpartum depression:a prospective cohort study and systematic literature review with meta-analysis

Importance:Postpartum depression (PPD) has a major impact on maternal and offspring well-being, with multiple possible risk factors: Studies on the association of thyroid peroxidase antibody (TPOAb) positivity and thyroid function with PPD provide heterogeneous results.Objective:To study the association of thyroid function and TPOAb positivity with PPD.Design:We assessed the association of TPOAb and thyroid function with PPD in a population-based prospective cohort study and performed a systematic literature review and meta-analysis.Methods:We measured thyroid stimulating hormone (TSH), free thyroxine (FT4), and TPOAb between 9- and 17-week gestation. Postpartum depression was assessed with Edinburgh Postpartum Depression Scale at 2-month postpartum and Brief Symptom Inventory at 2-, 6-, and 36-month postpartum. Additionally, we performed a systematic literature review and meta-analysis assessing this association.Results:In the present study, there was no association of thyroid function with PPD (TSH: odds ratio [OR] 0.83, 95% CI 0.58-1.19, P = .32; FT4: OR 0.99, 95% CI 0.95-1.05, P = .86) or TPOAb positivity with PPD (OR 0.79, 95% CI 0.47-1.33, P = .37). An impaired thyroidal response to human chorionic gonadotropin (hCG), a surrogate marker for TPOAb positivity, was associated with a lower risk of PPD (P for interaction TSH = 0.04; FT4 = 0.06). Our systematic review and meta-analysis included 3 articles that were combined with the present study. There was no statistically significant association of TPOAb positivity with PPD (OR 1.93, 95% CI 0.91-4.10, P = .08), but the results were heterogeneous (I2 = 79%).Conclusions and relevance:There was no significant association of TPOAb positivity, TSH, or FT4 with PPD. Our systematic review and meta-analysis revealed high heterogeneity of the current literature. Although TPOAb-positive women should be monitored for postpartum thyroiditis, our findings do not support routinely screening for PPD

Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study

Contains fulltext : 96669.pdf (publisher's version ) (Open Access)INTRODUCTION: Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-alpha) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-alpha blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-alpha blocking therapy in AS patients in daily clinical practice. METHODS: AS outpatients who started TNF-alpha blocking therapy were included in the Groningen Leeuwarden Ankylosing Spondylitis (GLAS) study, an ongoing prospective longitudinal observational cohort study with follow-up visits according to a fixed protocol. For the present analysis, patients were excluded if they had previously received anti-TNF-alpha treatment. Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models, respectively. RESULTS: Between November 2004 and April 2010, 220 patients started treatment with infliximab (n = 32), etanercept (n = 137), or adalimumab (n = 51). At three and six months, 68% and 63% of patients were Assessments in Ankylosing Spondylitis (ASAS)20 responders, 49% and 46% ASAS40 responders, and 49% and 50% Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 responders, respectively. Baseline predictors of response were younger age, male gender, higher ASDAS score, higher erythrocyte sedimentation rate (ESR) level, higher C-reactive protein (CRP) level, presence of peripheral arthritis, higher patient's global assessment of disease activity, and lower modified Schober test. In August 2010, 64% of patients were still using their TNF-alpha blocking agent with a median follow-up of 33.1 months (range 2.4 to 68.2). Baseline predictors of discontinuation of TNF-alpha blocking therapy were female gender, absence of peripheral arthritis, higher BASDAI, lower ESR level, and lower CRP level. CONCLUSIONS: Besides younger age and male gender, objective variables such as higher inflammatory markers or ASDAS score were identified as independent baseline predictors of response and/or continuation of TNF-alpha blocking therapy. In contrast, higher baseline BASDAI score was independently associated with treatment discontinuation. Based on these results, it seems clinically relevant to include more objective variables in the evaluation of anti-TNF-alpha treatment