Kai-Chun Wang

Bio: Kai-Chun Wang is an academic researcher from Taipei Veterans General Hospital. The author has contributed to research in topics: Rheumatoid arthritis & Endoscopic retrograde cholangiopancreatography. The author has an hindex of 2, co-authored 2 publications receiving 9 citations. Previous affiliations of Kai-Chun Wang include National Yang-Ming University.

IgG4-related disease coexisting with autoimmune haemolytic anaemia.

Abstract: An 85-year-old man presented with a pale appearance and generalised pruritic papules. Laboratory investigations disclosed eosinophilia, autoimmune haemolytic anaemia, mixed hyperbilirubinaemia, cholestasis and elevated serum IgG4 levels. Abdominal sonography and CT showed progressive dilatation of biliary trees, with diffuse pancreatic enlargement and a subtle capsule-like low-density rim around the pancreatic head and body. Endoscopic retrograde cholangiopancreatography found no stone-related biliary obstruction, while endoscopic transpapillary biopsy demonstrated chronic inflammation only. Nevertheless, the diagnosis of IgG4-related disease with coexisting autoimmune haemolytic anaemia was presumed. The clinical picture and laboratory abnormalities improved after administration of moderate dose of methylprednisolone.

Real-world effectiveness and safety of rituximab in the treatment of rheumatoid arthritis: A single-center experience in Taiwan.

Abstract: Aim To assess the real-world effectiveness and safety of rituximab (RTX) at 24 months in patients with established rheumatoid arthritis (RA) and to identify predictors of low disease activity/remission and a good European League Against Rheumatism (EULAR) response. Methods Seventy RTX-treated RA patients were enrolled. Predictors for low disease activity/remission and a good EULAR response at 24 months were identified by multivariate analyses. Results At 24 months, the mean Disease Activity Score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) decreased from 6.88 ± 0.85 at baseline to 3.47 ± 0.85. Twenty-nine patients (41.4%) reached low disease activity/remission, while all patients had a moderate/good EULAR response. After adjustment by multivariate analyses, we found concomitant methotrexate at a dosage >10 mg/week (odds ratio [OR] 5.17; 95% CI 1.34-19.93; P = 0.017) predicted low disease activity/remission, and baseline DAS28 ≤6.5 (OR 4.97; 95% CI 1.22-20.30; P = 0.026) predicted good EULAR response at 24 months. The most common adverse events were infusion-related (5.7%), and there was no incidence of malignancy or mortality during the treatment. Conclusions RTX was effective and safe in real-life management of RA patients with high disease activity. Patients taking concomitant methotrexate and with lower baseline DAS28-ESR were more likely to benefit from RTX.

Pemphigus: Current and Future Therapeutic Strategies

Abstract: Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.

A comprehensive review of rituximab therapy in rheumatoid arthritis patients

Abstract: Rituximab (RTX) is an approved treatment for rheumatoid arthritis (RA) patients that do not respond adequately to disease-modifying antirheumatic drugs. However, different new concerns, such as efficacy, optimum dose, safety issues, prediction of response to RTX, and pregnancy outcomes have attracted a lot of attention. The PubMed database was systematically reviewed for the last published articles, new findings, and controversial issues regarding RTX therapy in RA using “Rheumatoid arthritis” AND “rituximab” keywords, last updated on June 18, 2019. From 1812 initial recorders, 162 studies met the criteria. Regarding the optimum dose, low-dose RTX therapy (2 × 500 mg) seems as effective as standard dose (2 × 1000 mg), safer, and more cost-effective. The most common reported safety challenges included de novo infections, false negative serologic tests of viral infections, reactivation of chronic infections, interfering with vaccination outcome, and development of de novo psoriasis. Other less reported side effects are infusion reactions, nervous system disorders, and gastrointestinal disorders. Lower exposure to other biologics, presence of some serological markers (e.g., anti-RF, anti-CCP, IL-33, ESR), specific variations in FCGR3A, FCGR2A, TGFβ1, IL6, IRF5, BAFF genes, and also EBV-positivity could be used to predict response to RTX. Although there is no evidence of the teratogenic effect of RTX, it is recommended that women do not expose themselves to RTX at least 6 months before the conception. Only a reversible reduction of B cell-count in the offspring may be the pregnancy-related outcome. Although RTX is an effective therapeutic option for RA, more studies on optimum doses, prevention of RTX-related side effects, prediction of RTX response, and safety during the pregnancy are required.

FRI0512 IGG4-Related Disease Is Associated with A History of Malignancy

Abstract: Background IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unclear etiology 1 . Some studies suggest that IgG4-RD predisposes patients to malignancy or is a forme fruste of cancer 2 , but we have frequently observed IgG4-RD patients with a history of malignancy preceding the clinical onset of IgG4-RD. Objectives We sought to determine whether a history of malignancy was more common among patients at the onset of IgG4-RD compared to controls. Methods We identified IgG4-RD patients with a history of invasive malignancy from a well-defined cohort of 125 patients and compared their malignancy history to those of two reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to five age- and gender-matched controls for each case and calculated the odds of malignancy among those with IgG4-RD compared to controls using conditional logistic regression. Results The mean age at IgG4-RD onset was 50.3±14.9 years and 61% of the patients were male. Twenty (16%) had been diagnosed with 21 malignancies before the diagnosis of IgG4-RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% CI:1.1–3.6) than expected compared to the SEER database. Compared with matched controls, a history of malignancy was more than three-fold higher in IgG4-RD (OR 3.1;95% CI:1.6–6.2). Conclusions Our findings suggest that malignancy is associated with the subsequent development of IgG4-RD in a subset of patients with IgG4-RD. Potential explanations include shared risk factors for both IgG4-RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4-RD, and an increased risk of IgG4-RD resulting from cancer treatment. References Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366(6):539–551. Hart PA, Law RJ, Dierkhising RA, Smyrk TC, Takahashi N, Chari ST. Risk of cancer in autoimmune pancreatitis: A case-control study and review of the literature. Pancreas. 2014;43(3):417–421. Disclosure of Interest None declared

Predictors of remission in rheumatoid arthritis patients treated with biologics: a systematic review and meta-analysis

Abstract: Biologics have emerged as an effective treatment of rheumatoid arthritis (RA). However, there is a significant proportion of patients who fail to respond to biologics. Identifying the predictors that affect the response to biologics remains challenging. A comprehensive literature search of PubMed, Embase, and Web of Science databases was conducted through May 1, 2022. We included all studies that used a multivariate model to assess for the predictors of remission in RA patients treated with biologics. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) for risk factors reported in ≥ 3 studies using a random-effects model. A total of 16,934 patients with RA who were treated with biologics were included in twenty-one studies. Our study showed that old age (OR 0.98 (0.97, 0.99), P < 0.00001), female gender (OR 0.66 (0.56, 0.77), P < 0.00001), smoking history (OR 0.86 (0.75, 0.99), P 0.04), obesity (OR 0.95 (0.91, 0.99), P 0.02), poor functional status (OR 0.62 (0.48, 1.27), P < 0.00001), high disease activity (OR 0.90 (0.85, 0.96), P 0.0005), and elevated erythrocyte sedimentation rate (OR 0.99 (0.98, 1.00), P 0.009) were poor predictors of remission. On the other hand, positive anti-citrullinated protein antibodies (OR 2.52 (1.53, 4.12), P 0.0003) was associated with high remission rate. Old age, female gender, obesity, smoking history, poor functional status, high disease activity, and elevated ESR at the time of diagnosis have been associated with poor response to biologics. Our findings could help establish a risk stratification model for predicting the remission rate in RA patients receiving biologics.