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ID PMID Title PublicationDate abstract
33166704 [Methotrexate: How long between administration and conception?]. 2021 Feb In women of childbearing age, methotrexate is prescribed in many indications other than cancer, either chronically (psoriasis, rheumatoid arthritis, IBD, etc.) or occasionally (ectopic pregnancies). The time given to these patients to consider pregnancy is currently subject to great variability depending on the sources. Analysis of the available objective evidence suggests that it is not justified to unnecessarily lengthen this period, and that conceiving the menstrual cycle following stopping methotrexate is quite possible.
33725321 Comparative Efficacy and Safety of Peficitinib Versus Tofacitinib and Baricitinib for Trea 2021 Jun INTRODUCTION: Peficitinib, a Janus kinase (JAK) inhibitor, is approved for clinical use in Japan, Korea, and Taiwan, but head-to-head comparisons versus other JAK inhibitors are lacking. We indirectly compared peficitinib, tofacitinib, and baricitinib for rheumatoid arthritis treatment. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congress archives up until February 12, 2019, for randomized controlled trials of peficitinib, tofacitinib, and baricitinib. Efficacy (American College of Rheumatology responses, disease activity scores, modified total Sharp score, Simplified Disease Activity Index [SDAI]) and safety outcomes were compared using a Bayesian network meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results. A network meta-regression assessed the impact on outcomes of proportions of patients receiving concomitant methotrexate or of Asian ethnicity. RESULTS: The network meta-analysis included 21 randomized controlled trials. At 12 weeks, all evaluable efficacy outcomes were comparable or improved with peficitinib 150 mg and 100 mg once daily, versus baricitinib 2 and 4 mg once daily and tofacitinib 5 mg twice daily. At 24 weeks, efficacy outcomes were comparable or improved for each peficitinib dose versus baricitinib and tofacitinib. Risk of adverse events and serious adverse events at 12 weeks were similar with peficitinib 100 and 150 mg versus baricitinib and tofacitinib. The proportion of patients receiving concomitant methotrexate had no effect on any outcome analyzed, but Asian ethnicity had a positive effect on multiple efficacy outcomes. CONCLUSIONS: Peficitinib had comparable efficacy versus tofacitinib and baricitinib for reduction in disease activity as measured by SDAI, and for reduction in progression of joint damage as measured radiographically. No notable differences in safety outcomes were observed. Further studies are required to better characterize the impact of ethnicity on the efficacy of JAK inhibitors.
34823825 Infections in systemic autoimmune diseases. 2021 Dec INTRODUCTION: Infections are a major cause of morbidity and mortality in patients with systemic autoimmune diseases. The aim of the present study is to describe the frequency of infections in a historical cohort of the SAD polyclinic of the Maciel Hospital, according to the type of disease and treatment received. MATERIAL AND METHODS: An analytical, retrospective and observational study was conducted in 339 patients with SAD attended at the outpatient clinic in the period from January 1, 2012 to February 28, 2019. Infectious complications were analysed according to treatment and disease. RESULTS: 339 cases, median age 56, mostly female. Most cases presented SLE (30.1%) and RA (23.6%), followed by antiphospholipid syndrome (20.4%) and Sjögren's syndrome (12.1%). Hydroxychloroquine (66%), followed by corticosteroids (55.5%) were the most frequently used treatments. Thirteen point three percent received biological therapies: 46.9% of the cases presented some infectious complication, 95% were non-opportunistic. Respiratory infections were the most frequent (48.6%) followed by urinary infections (31.7%) and skin and soft tissue infections (17.6%). On comparing the infected and non-infected groups, significant differences were found in the following variables: methotrexate, mycophenolate, corticoids, biological therapies, combination of drugs, active disease, RA and cases with overlap. The use of hydroxychloroquine and sulfasalazine was associated with a lower risk of infection in patients with RA. CONCLUSIONS: Infections are a frequent complication in patients with RA, due to the immune disturbances of the disease itself and prescribed treatments, mainly corticoids and biologicals. The importance of screening and infection prophylaxis before starting treatment is stressed.
34452007 Impact of Low-Dose Methotrexate-Adalimumab Combination Therapy on the Antibody Response In 2021 Aug 9 Patients with rheumatoid arthritis (RA) are treated with drugs that may impact their immune responses to SARS-CoV-2 vaccines. We describe here the anti-Spike (anti-S) IgG and neutralizing antibody responses induced by the mRNA-1273 SARS-CoV-2 vaccine in a 78-years-old patient with RA, who received a low-dose combination therapy of methotrexate and adalimumab, shortly before vaccine administration. Both near-normal and impaired immune responses to vaccines have been reported previously in patients treated with these drugs. Our case report shows that, even at low doses, combined methotrexate-adalimumab therapy can be associated with a weak immune response to the mRNA1273 vaccine in elderly patients.
34085401 What Is the Persistence to Methotrexate in Rheumatoid Arthritis, and Does Machine Learning 2021 Jul OBJECTIVE: The objectives of this study were to assess the 1-year persistence to methotrexate (MTX) initiated as the first ever conventional synthetic disease-modifying antirheumatic drug in new-onset rheumatoid arthritis (RA) and to investigate the marginal gains and robustness of the results by increasing the number and nature of covariates and by using data-driven, instead of hypothesis-based, methods to predict this persistence. METHODS: Through the Swedish Rheumatology Quality Register, linked to other data sources, we identified a cohort of 5475 patients with new-onset RA in 2006-2016 who were starting MTX monotherapy as their first disease-modifying antirheumatic drug. Data on phenotype at diagnosis and demographics were combined with increasingly detailed data on medical disease history and medication use in four increasingly complex data sets (48-4162 covariates). We performed manual model building using logistic regression. We also performed five different machine learning (ML) methods and combined the ML results into an ensemble model. We calculated the area under the receiver operating characteristic curve (AUROC) and made calibration plots. We trained on 90% of the data, and tested the models on a holdout data set. RESULTS: Of the 5475 patients, 3834 (70%) remained on MTX monotherapy 1 year after treatment start. Clinical RA disease activity and baseline characteristics were most strongly associated with the outcome. The best manual model had an AUROC of 0.66 (95% confidence interval [CI] 0.60-0.71). For the ML methods, Lasso regression performed best (AUROC = 0.67; 95% CI 0.62-0.71). CONCLUSION: Approximately two thirds of patients with early RA who start MTX remain on this therapy 1 year later. Predicting this persistence remains a challenge, whether using hypothesis-based or ML models, and may yet require additional types of data.
34913611 Pain Reduction in Rheumatoid Arthritis Patients Who Use Opioids: A Post Hoc Analysis of Ph 2022 Mar OBJECTIVE: Pain reduction with baricitinib was assessed in patients with rheumatoid arthritis (RA) who either used opioids or did not use opioids during three randomized, double-blind phase 3 trials. METHODS: Analysis populations were as follows: i) baricitinib 4 mg once daily versus placebo groups integrated from RA-BEAM (NCT01710358) for patients with inadequate response (IR) to methotrexate, RA-BUILD (NCT01721057) with IR to conventional disease-modifying antirheumatic drugs, and RA-BEACON (NCT01721044) with IR to at least one tumor necrosis factor inhibitors; ii) baricitinib 2 mg versus placebo from RA-BUILD and RA-BEACON; and iii) adalimumab 40 mg every other week versus placebo from RA-BEAM. Pain was measured by the Patient Assessment of Pain Visual Analog Scale. Analysis of covariance modeling assessed differences in pain reduction between treatments at each time point through Week 24, with an interaction term to test heterogeneous treatment effects across opioid users and nonusers. RESULTS: Baricitinib 4 mg had greater pain reduction versus placebo in opioid users and nonusers (P < 0.05) at all time points starting from Week 1; the pain reduction was similar between opioid users and nonusers. Baricitinib 2 mg had greater pain reduction versus placebo in opioid users and nonusers starting at Week 4. A significant difference in pain reduction was not observed for adalimumab versus placebo in the opioid users but was observed in nonusers at all time points. CONCLUSION: Pain reduction was observed and was similar between opioid users and nonusers with baricitinib 2 mg and 4 mg but not adalimumab in this post hoc analysis.
33505476 Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Rea 2021 Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular destruction and functional loss. Methotrexate (MTX) is effective in RA treatment. However, MTX induces several adverse events and 20%-30% of patients do not respond to MTX. Thus, it is urgent to enhance the therapeutic effects and reduce the side effects of MTX. Recent studies showed that mesenchymal stem cells (MSCs) were participants in anti-inflammation, immunoregulation, and tissue regeneration. However, whether the combined application of MSCs and MTX promotes the therapeutic effects and reduces the side effects of MTX has not been studied. In this study, we used bovine type II collagen to induce rheumatoid arthritis in mice (collagen-induced arthritis, CIA). Then, CIA mice were subjected to MTX or MSC treatment, or both. The therapeutic effect and adverse events of different treatments on RA were evaluated with micro-CT, HE staining, and immunohistochemistry in vivo. Apoptosis and proliferation of MODE-K cells were measured after treated with MTX or/and cocultured with UCs. To test M2 polarization, Raw264.7 macrophages were stimulated by MTX with different concentrations or cocultured with UCs. We found that the combined application of MSCs and MTX increased the therapeutic effects on RA, as evidenced by decreased arthritis score, inflammatory responses, and mortality. Moreover, in this combination remedy, MTX prefers to suppress inflammation by facilitating macrophage polarization to M2 type while UCs prefer to eliminate gastrointestinal side effects of MTX via mitigating the apoptosis of intestinal epithelial cells. Thus, a combination of MTX and UCs is a promising strategy for RA treatment.
34060254 Exploring the Role of Antinuclear Antibody Positivity in the Diagnosis, Treatment, and Hea 2021 Jun OBJECTIVE: The objective of this study was to describe differences in the clinical course of patients with rheumatoid arthritis (RA) who are antinuclear antibody (ANA)-positive compared with those who are ANA-negative. METHODS: This was a retrospective population-based cohort study of residents in Olmsted County, Minnesota, who first fulfilled 1987 American College of Rheumatology criteria for RA in 2009-2014. Data were collected on first documentation of joint swelling. Data on rheumatoid factor or anti-cyclic citrullinated peptide antibody testing and the ANA level were also collected. Comparisons between groups were performed by using χ(2) and rank sum tests. RESULTS: In this cohort, 64% of patients were tested for ANA within ±90 days of RA criteria fulfillment. In the161 patients with ANA testing, 25% were ANA-positive. Patients who were ANA-positive were younger, female, and less likely to be current smokers. ANA positivity did not differ between patients with RA who were seropositive and seronegative. In seropositive patients who were ANA-positive, there was an increased time to fulfillment of RA criteria, increased time to treatment with disease-modifying antirheumatic drugs (DMARDs), and increased likelihood of being treated with hydroxychloroquine as opposed to methotrexate. Other outcomes, including disease activity and mortality, did not differ significantly between groups. CONCLUSION: In patients with RA, important differences exist between those who are ANA-positive and ANA-negative in terms of time to fulfillment of RA criteria and time to DMARD initiation as well as choice of initial pharmacotherapy. These findings could indicate a difference in clinical presentation or perception of patients with RA who are ANA-positive. Further research is needed to study the long-term outcomes of patients with RA who are ANA-positive.
33623411 Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rat 2021 BACKGROUND: The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown. MATERIALS AND METHODS: The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses. Protein expression in tissues and cells was investigated by either immunohistochemical or immunoblotting methods, while levels of mRNA expression were investigated by RT-qPCR. Metabolites in serum were detected by LC-MS approach. The joints homogenates were used for analyzing possible targeted genes by genome microarray analyses. RESULTS: Treatment with XRF and methotrexate (MTX) led to significant decrease in arthritis scores, and alleviated deformation of paws in CIA rats. In addition, XRF and MTX reduced circulating TNF-α, IL-1β and IL-17α in the serum and down-regulated TLR4/NF-κB and JNK pathways in joints of CIA rats. Compared to MTX, XRF-loading microemulsion significantly protected joints, which was accompanied by dramatic decrease in MMP3. Differential genes-based KEGG enrichment and metabolomics analysis suggested that XRF reduced fatty acids biosynthesis by regulating PPAR-γ signaling. S inappendiculata-derived 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) up-regulated PPAR-γ expression in macrophages, but suppressed it in pre-adipocytes in vitro, which was synchronized with SIRT1 changes. Adiponectin production and SCD-1 expression in pre-adipocytes were also decreased. Aside the direct inhibition on MMP3 expression in synovioblast, the presence of XAN in macrophages-pre-adipocytes co-culture system further reinforced this effect. CONCLUSION: This study revealed the joint protective  advantages of the bioactive fraction from S. inappendiculata in CIA rats over MTX, and demonstrated that S. inappendiculata-derived xanthones suppressed the erosive nature of synovioblast acquired under inflammatory circumstances by regulating PPAR-γ signaling-controlled metabolism-immunity feedback.
34806155 Fine Comparison of the Efficacy and Safety Between GB242 and Infliximab in Patients with R 2022 Feb INTRODUCTION: This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade(®)) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. METHODS: Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity. RESULTS: A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62-68.20%) and 56.89% for the INF group (95% CI 50.90-62.74%). The difference between the two groups was 5.65% with a 95% CI of - 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable. CONCLUSIONS: GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.
34113254 Traditional Chinese Medicine Qingre Huoxue Treatment vs. the Combination of Methotrexate a 2021 Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). Qingre Huoxue treatment (Qingre Huoxue decoction (QRHXD)/Qingre Huoxue external preparation (QRHXEP)) is a therapeutic scheme of TCM for RA. To date, there have been few studies comparing the efficacy and safety of QRHXD and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of active RA. This was investigated in a multicenter, double-blind, randomized controlled trial involving 468 Chinese patients with active RA [disease activity score (DAS)-28 > 3.2] treated with QRHXD/QRHXEP (TCM group), methotrexate plus hydroxychloroquine [Western medicine (WM) group], or both [integrative medicine (IM) group]. Patients were followed up for 24 weeks. The primary outcome measure was the change in DAS-28 from baseline to 24 weeks. The secondary outcome measures were treatment response rate according to American College of Rheumatology 20, 50, and 70% improvement criteria (ACR-20/50/70) and the rate of treatment-related adverse events (TRAEs). The trial was registered at ClinicalTrials.gov (NCT02551575). DAS-28 decreased in all three groups after treatment (p < 0.0001); the score was lowest in the TCM group (p < 0.05), while no difference was observed between the WM and IM groups (p > 0.05). At week 24, ACR-20 response was 73.04% with TCM, 80.17% with WM, and 73.95% with IM (based on the full analysis set [FAS], p > 0.05); ACR-50 responses were 40.87, 47.93, and 51.26%, respectively, (FAS, p > 0.05); and ACR-70 responses were 20.87, 22.31, and 25.21%, respectively, (FAS, p > 0.05). Thus, treatment efficacy was similar across groups based on ACR criteria. On the other hand, the rate of TRAEs was significantly lower in the TCM group compared to the other groups (p < 0.05). Thus, QRHXD/QRHXEP was effective in alleviating the symptoms of active RA-albeit to a lesser degree than csDMARDs-with fewer side effects. Importantly, combination with QRHXD enhanced the efficacy of csDMARDs. These results provide evidence that QRHXD can be used as an adjunct to csDMARDs for the management of RA, especially in patients who experience TRAEs with standard drugs. Clinical Trial Registration: ClinicalTrials.gov, identifier NCTNCT025515.
33884025 Effect of Moxibustion on β-EP and Dyn Levels of Pain-Related Indicators in Patients with 2021 BACKGROUND: Rheumatoid arthritis (RA) is a systemic immunodeficiency disease characterized by persistent synovial inflammation, pannus formation, and bone and cartilage destruction, resulting in joint malformations and function decline. OBJECTIVE: The purpose of this study is to evaluate the effect of moxibustion on clinical symptoms and levels of pain-related indicators beta-endorphin (β-EP) and dynorphin (Dyn) in patients with RA and to explore the potential anti-inflammatory and analgesic mechanisms of moxibustion in RA treatment. METHODS: A total of 64 patients with RA who met the inclusion criteria were randomly and equally classified into the control and treatment groups. The control group received conventional treatment (oral methotrexate, folate, or leflunomide prescribed for a long time). The treatment group was treated with moxibustion at ST36 (Zusanli), BL23 (Shenshu), and Ashi points with respect to the control group. Patients' clinical symptoms and routine inspection indexes (rheumatoid factor [RF], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]) were recorded before and after treatment. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), β-EP, and Dyn were determined by enzyme-linked immunosorbent assay (ELISA). The software SPSS24.0 was used for statistical analysis. RESULTS: (1) Compared with the pretreatment result, both of the two groups' clinical symptoms and routine inspection indexes (RF, ESR, and CRP) improved (P < 0.05), and the improvement of clinical symptoms in the treatment group outperformed that in the control group (P < 0.05). (2) TNF-α and IL-1β levels decreased significantly in the treatment group after treatment (P < 0.01), while no significant difference was observed in the control group (P > 0.05). (3) β-EP and Dyn levels in the treatment group were significantly increased after treatment (P < 0.01, P < 0.01), but the control group showed no significant difference (P > 0.05, P > 0.05). It is worth mentioning that the serum TNF-α, IL-1β, β-EP, and Dyn levels between the two groups were significantly different after 8 weeks of treatment (P < 0.05). (4) Differences in the serum β-EP and Dyn levels in the patients of the treatment group were correlated with TNF-α and IL-1β levels after treatment, and the correlation was mainly negative (r < 0). CONCLUSION: Moxibustion can improve joint pain in patients with RA using conventional western medicine. One of the mechanisms may affect the serum β-EP and Dyn levels by downregulating the inflammatory factors to play an anti-inflammatory and analgesic role.
33164739 Treating rheumatoid arthritis with leflunomide monotherapy versus combination therapy with 2021 Jan OBJECTIVE: Combination therapies have been proposed as a strategy to control inflammation more effectively in patients with rheumatoid arthritis (RA). Few studies examine the combined effect of methotrexate (MTX) and leflunomide (LFN). This study evaluated the symptom control and side effects of the combination of MTX and LFN compared with LFN monotherapy. METHODS: We conducted a retrospective analysis of 113 patients with RA treated with either LFN alone (n=22) or in combination with MTX (n=91). Data on disease activity score 28 erythrocyte sedimentation rate (DAS-28 ESR), DAS-28 C-reactive protein (DAS-28 CRP), blood cell count, liver enzymes, and creatinine levels were determined. Samples were collected on day 0 (initiation of LFN) and at 6 and 12 months. RESULTS: We found no differences between the 2 groups in DAS-28 on day 0 and at 6 and 12 months (p=0.89, p=0.42, and p=0.09, respectively, for DAS-28 ESR; p=0.97, p=0.27, and p=0.63, respectively, for DAS-28 CRP). In addition, we observed no differences in the blood cell count, liver enzymes, and creatinine levels between the treatment groups at any of the time points (all p>0.05). CONCLUSION: Our results suggest that the efficacy of the combined treatment with MTX and LFN is similar to that of LFN alone. No increase in toxicity was observed with the combination therapy.
34796837 Blood chemokine levels are markers of disease activity but not predictors of remission in 2021 Nov 3 OBJECTIVES: In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated eRA. METHODS: This study included 347 Swedish patients with untreated eRA from the larger NORD-STAR randomised treatment trial. Here, eRA patients were treated with methotrexate combined with either prednisolone, anti-TNF (certolizumab-pegol), CTLA-4Ig (abatacept) or anti-IL6 receptor (tocilizumab). The primary clinical outcome was remission by clinical disease activity index (CDAI) defined as CDAI ≤ 2.8. Disease activity was assessed by CDAI, DAS28-ESR, DAS28-CRP, swollen joint counts, tender joint counts, ESR and CRP. The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or ELISA. RESULTS: Baseline plasma concentrations of CXCL10, CXCL8, CXCL9, CXCL11, CXCL5 and CCL2 correlated with baseline disease activity measures. After 24 weeks of treatment, plasma levels of CXCL10, CXCL8, CXCL9, CXCL11 and CXCL13 decreased in all treatment groups except in patients treated with anti-IL6 receptor. In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups. CONCLUSIONS: In patients with untreated eRA, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti‑TNF, CTLA‑4Ig or anti‑IL6R.
34190324 Inflammatory Arthritis Among Military Servicemen From a Rheumatology Center in Singapore. 2021 Jun 30 INTRODUCTION: Musculoskeletal disorders are one of the most common reasons military servicemen seek medical care during their line of duty. This study aims to review the clinical profile and outcomes of military personnel with inflammatory arthritis (IA) referred to a specialist rheumatology center in Singapore. MATERIALS AND METHODS: Consecutive new case referrals from the Singapore Armed Forces medical centers during the study period January 1, 2010, to December 31, 2019, were retrospectively studied. RESULTS: There were 123 referrals, comprising 112 (91.1%) males, with the majority being Chinese (110, 89.4%). The mean age was 25.5 ± 11.1 years. The most common diagnoses were gout (including chronic tophaceous gout; 34, 27.6%), spondyloarthritis (18, 14.6%), palindromic rheumatism (8, 6.5%), rheumatoid arthritis (4, 3.3%), and juvenile idiopathic arthritis (4, 3.3%). Among servicemen with gout, all were male, the majority (31, 91.3%) were Chinese, and mean age was 34.1 ± 8.8 years. Mean body mass index (BMI) was 27.5 ± 3.9 kg/m2, of which 41.2% had moderate-risk and 47.1% high-risk BMI for cardiovascular disease and diabetes mellitus (DM). Comorbidities included hyperlipidemia (14), hypertension (6), and type 2 DM (3). Urate lowering therapy was initiated in 27 (79.4%) patients, comprising allopurinol (85.2%), probenecid (11.1%), and their combination (3.7%). One patient developed allopurinol-induced hepatitis; none had severe cutaneous adverse reactions. Among the remaining patients with IA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) used were sulfasalazine (8), methotrexate (4), hydroxychloroquine (4), and leflunomide (2). Biologic DMARDs used in five patients comprised adalimumab (3) and golimumab (2). CONCLUSION: Servicemen with IA and good functional status can still be physically fit and deployable into certain combat and service support vocations. This will optimize manpower resources in military organizations with a shrinking young workforce.
33634720 EBV Positive Lymphomatoid Granulomatosis Following Dental Extractions. 2021 Feb 26 Epstein-Barr virus (EBV) associated lymphoproliferative disorders includes a diverse group of diagnoses, encompassing both B-cell and T-cell lineages. With EBV mucocutaneous ulcers becoming a World health Organization diagnosis in 2018, introduction of the disease entity will be beneficial to the practicing otolaryngologist. We are reporting a case of a 69-year-old male with history of rheumatoid arthritis on methotrexate, recently undergoing dental extractions, who then developed multiple oral ulcerations and bony erosions of his palate and alveolar ridge. Associated symptoms included a large 3.0 cm neck mass, splenomegaly, and pulmonary nodules. Histopathology showed EBV+ lymphomatoid granulomatosis. Upon removal of immunosuppressive agent, patient's symptoms improved with resolution of oral lesions, as well as systemic symptoms.
33912248 Prevalence, therapy and tumour response in patients with rheumatic immune-related adverse 2021 BACKGROUND: Immune checkpoint inhibitors (ICIs) improved cancer therapy by inducing a higher immune system activity. This effect can cause rheumatic immune-related adverse events (rh-irAEs), which have not yet been extensively studied. METHODS: We analysed 437 patients between 2014 and 2019, treated with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) at the Clinic for Internal Medicine III, Oncology, Haematology and Rheumatology at the University Hospital Bonn, Germany. RESULTS: Of the 437 patients 60% were males. Patients were mainly treated for melanoma, lung cancer, head and neck tumour and urothelial carcinoma. At least one immune-related adverse event (irAE) was observed in 163 patients (37.3%), including rh-irAE. Most common side effects were rash, colitis and hepatitis. We identified 19 patients (4.3%) with a minimum of one rh-irAE due to ICI therapy; three of those had a pre-existing rheumatic disease. Arthralgia developed most frequently in eight patients (42.1%). Other rh-irAEs were: arthritis (n = 7; distinguished in rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and undifferentiated arthritis), myalgia (n = 2) and myositis (n = 3). Most rh-irAEs were classified as moderately severe (Common Terminology Criteria of Adverse Events grade 2: 68.4%). Median time between starting ICI therapy and the occurrence of rh-irAE was 109 days (interquartile range 40-420 days). Fifteen patients (78.9%) were treated with glucocorticosteroids. In four cases additional therapy with methotrexate or tocilizumab was required. Even though patients benefited from ICI treatment, therapy had to be discontinued in six of the participants due to rh-irAE. Interestingly, patients with rh-irAE had a significantly higher tumour response compared with patients without rh-irAE (94.4% versus 43.5%; p < 0.0001). CONCLUSION: Rh-irAEs occur under ICI therapy, especially in patients with higher tumour response. However, they are not the most frequent irAE after ICI exposure: 9.3% of all irAEs were rheumatic (20 rh-irAE cases in 19 patients of a total of 215 irAE cases in 163 patients).
33651370 Prescribing Patterns and Impact of Factors Associated with Time to Initial Biologic Therap 2021 Mar OBJECTIVE: The aim of this study was to examine patterns of initial prescriptions, investigate time to initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs), and evaluate the impact of clinical and other baseline factors associated with the time to first bDMARD in treating children with newly diagnosed non-systemic juvenile idiopathic arthritis (JIA). METHODS: Using longitudinal patient-level data extracted from electronic medical records (EMR) in a large Midwestern pediatric hospital from 2009 to 2018, the initial prescriptions and prescribing patterns of bDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids within 3 months of JIA diagnosis were examined. Kaplan-Meier analyses were performed to assess time to initiation of bDMARDs. Cox proportional hazard models were used to identify factors associated with time to first bDMARD. RESULTS: Of 821 children, the proportion of patients with initial csDMARDs increased from 45.3% in 2009 to 60.3% in 2018. Around 57.5% of polyarthritis rheumatoid factor-positive (Poly RF+) patients and 43.2% of polyarthritis rheumatoid factor-negative (Poly RF-) patients received a bDMARD therapy within 3 months of diagnosis, 14.4% as monotherapy and 28.3% in combination with a csDMARD. Among patients who received combination therapy, combination of methotrexate with adalimumab increased from 16.7% in 2009 to 40% in 2018. The proportion of patients treated with adalimumab gradually increased and passed etanercept in 2016. The predictors of earlier initiation of biologic therapy were JIA category enthesitis-related arthritis (ERA) [hazard ratio (HR) vs persistent oligoarthritis 4.82; p < 0.0001], psoriatic arthritis (PsA) (HR 2.46; p = 0.0002), or Poly RF- (HR 2.43; p = 0.0002); the number of joints with limited range of motion (HR 1.02; p = 0.0222), and erythrocyte sedimentation rate (ESR, HR 1.01; p = 0.0033). CONCLUSIONS: There was a substantial increase in the proportion of patients receiving the combination of methotrexate and adalimumab among patients receiving combination therapy. Adalimumab overtook etanercept as the most frequently prescribed bDMARD. Multiple factors affect the time to biologic initiation, including the number of joints with limited range of motion, ESR, and JIA category.
33938438 Leprosy as a Diagnostic Challenge in the United States. 2021 A 63-year-old woman from Central Florida presented to an outside clinic with a 2-year history of a progressive, asymptomatic cutaneous eruption and arthralgias. Her past medical history was significant for reported seronegative rheumatoid arthritis, for which adalimumab, methotrexate, and low-dose prednisone therapy were initiated 5 years prior. The skin eruption occurred shortly after a 4-week hospitalization during which these medications were withheld. At her initial outside evaluation, a biopsy was performed and interpreted as subacute cutaneous lupus erythematosus (SCLE). She was treated with hydroxychloroquine without improvement. A repeat biopsy was reported as consistent with interstitial granulomatous dermatitis (IGD). There was no improvement with potent topical corticosteroids.
33259751 Clinical features and outcomes from the Singapore Sjögren's syndrome study. 2021 Feb OBJECTIVE: To study the clinical features, treatment and outcomes of primary Sjögren's Syndrome (pSS) in a Singapore cohort from an outpatient rheumatology clinic. METHODS: Computerised Physician Order entry records of patients who fulfilled the 2016 ACR-EULAR classification criteria for pSS between 1993 and 2013 were retrospectively analysed. RESULTS: There were 102 patients, of which 96 (94.1%) were females, and 91 (89.2%) Chinese. Mean age at diagnosis was 49.3 ± 11.8 years, mean disease duration was 9.0 ± 4.6 years. The most common manifestations were keratoconjunctivitis sicca (99.0%), xerostomia (96.1%), arthralgia/arthritis (56.9%). Exocrine glandular enlargement comprised parotidomegaly (28, 27.5%), with concurrent submandibular and lacrimal gland enlargement in one. The nervous system (15.7%) was the most commonly affected internal organ, with peripheral nervous system (peripheral neuropathy, mononeuritis multiplex) involvement more common than central. Hydroxychloroquine was most frequently used (88.2%), followed by methotrexate (7.8%) and azathioprine (6.9%). Pulsed intravenous (IV) methylprednisolone 500 mg/day for 3 days was used in 5 patients followed by oral (4) or IV cyclophosphamide (1) for cardiomyopathy and interstitial lung disease (1), and neurological involvement (4). These comprised neuromyelitis optica, transverse myelopathy, cranial neuropathy, mononeuritis multiplex and/or peripheral neuropathy alone or in combination. Intravenous immunoglobulins (2.0%) was used for sensory neuropathy and mononeuritis multiplex; rituximab (1.0%) in 1 patient for treatment of non-Hodgkin's B-cell lymphoma. There were no deaths. CONCLUSION: Musculoskeletal manifestations were common, with the nervous system (peripheral more than central) the most common internal organ involved. Lymphoma was uncommon despite up to one-third of the cohort developing glandular enlargement.