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ID PMID Title PublicationDate abstract
34505213 Lifestyle factors in patients with rheumatoid arthritis-a cross-sectional study on two Sca 2022 Feb INTRODUCTION: The risk for cardiovascular diseases and other comorbidities increases with the number of unhealthy lifestyle factors in the general population. However, information on the combined number of unhealthy lifestyle factors in people with rheumatoid arthritis (RA) is scarce. OBJECTIVES: To study lifestyle factors and the association between disease impact and two or more unhealthy lifestyle factors in two Scandinavian cohorts with RA. METHODS: We analysed data from two cohorts, Danish (n = 566; mean age 61.82 (SD 11.13) years; 72% women) and Swedish (n = 955; mean age 66.38 (SD 12.90) years; 73% women). Lifestyle factors (tobacco use, BMI, alcohol consumption and physical activity) were dichotomised as healthy vs. unhealthy (range 0-4 unhealthy factors). The association between disease impact and two or more unhealthy lifestyle factors was analysed using logistic regression. RESULTS: Sixty-six percent of Danish and 47% of Swedish respondents reported two or more unhealthy lifestyle factors, most commonly, being overweight/obese and physical inactivity. For Danish participants, two or more unhealthy lifestyle factors were associated with (OR and 95% CI) male gender (1.86; 1.21-2.85), cardiovascular diseases (1.90; 1.28-2.82) and disease duration (0.97; 0.95-0.99). Corresponding findings for the Swedish cohort were male gender (1.42; 1.07-1.89), pain (1.10; 1.04-1.15), fatigue (1.09; 1.04-1.15), physical functioning (1.64; 1.28-2.10) and quality of life (0.35; 0.20-0.60). CONCLUSION: Many patients, most often male, in both cohorts had two or more unhealthy lifestyle factors. The number of unhealthy lifestyle factors indicates a multifaceted relationship with disease impact.
35142903 Neglected tropical rheumatic diseases. 2022 May The complexities of dealing with rheumatic diseases in tropical countries are diverse and likely due to limited health care infrastructure, lack of diagnostic and therapeutic facilities, impact of dominant prevailing diseases, and the challenges of differentiating from infectious and non-infectious disease mimics. Several tropical diseases present with musculoskeletal and rheumatic manifestations and often pose a diagnostic dilemma to rheumatologists. The diagnosis is often delayed or the disease is misdiagnosed, leading to poor patient outcomes. Endemic tropical diseases like tuberculosis and leprosy have myriad rheumatic presentations and remain important differentials to consider in patients with rheumatic manifestations. Infection with human immunodeficiency virus is a great masquerade and can mimic manifestations of multiple diseases. The role of viral infections in triggering and perpetuating autoimmunity is well known and chikungunya arthritis is a classic example of the same. This review highlights the rheumatic manifestations of tropical diseases and aims to create awareness among the caregivers. Key Points • It is crucial to be aware and identify infectious diseases presenting with rheumatic manifestations in the tropics. • Presentations akin to classic rheumatic syndromes such as rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus and vasculitis are common.
35228398 Infliximab Treatment Persistence among Japanese Patients with Chronic Inflammatory Disease 2022 Infliximab (IFX) has contributed to the treatment of several chronic inflammatory diseases, including Crohn's disease (CD), ulcerative colitis (UC), psoriasis (Pso), and rheumatoid arthritis (RA). However, the loss of response in some patients with long-term IFX therapy has been a major problem. Randomized controlled trials (RCTs) are limited in their short duration and lack of generalizability to the real-world population. We aimed to describe the persistence rates of IFX therapy to estimate its long-term effectiveness in clinical practice. Claims data from the Japan Medical Data Center database from January 2005 to June 2017 were used. The study population was identified based on the International Classification of Diseases, 10th Revision and the Anatomical Therapeutic Chemical Classification System. The 5-year persistence rates of IFX therapy were estimated using the Kaplan-Meier method. Overall, 281, 235, 41, and 222 patients with CD, UC, Pso, and RA, respectively, were selected. The 5-year persistence rates for IFX claims were 62.9, 38.9, 22.1, and 28.1% in patients with CD, UC, Pso, and RA, respectively. Patients with CD and UC administered IFX beyond the median dose had higher persistence rates. In patients with RA, female sex and no prior use of other biologics were associated with longer persistence. In conclusion, IFX persistence rates differed across chronic inflammatory diseases, which did not correspond to the results of the major RCTs. Factors associated with longer IFX persistence were identified in each disease group. Our findings may provide useful information to facilitate the proper use of IFX.
35224112 Oral and Intestinal Bacterial Substances Associated with Disease Activities in Patients wi 2022 Intestinal bacterial compositions of rheumatoid arthritis (RA) patients have been reported to be different from those of healthy people. Dysbiosis, imbalance of the microbiota, is widely known to cause gut barrier damage, resulting in an influx of bacteria and their substances into host bloodstreams in animal studies. However, few studies have investigated the effect of bacterial substances on the pathophysiology of RA. In this study, eighty-seven active RA patients who had inadequate responses to conventional synthetic disease-modifying antirheumatic drugs or severe comorbidities were analyzed for correlations between many factors such as disease activities, disease biomarkers, intestinal bacterial counts, fecal and serum lipopolysaccharide (LPS), LPS-binding protein (LBP), endotoxin neutralizing capacity (ENC), and serum antibacterial substance IgG and IgA antibody levels by multiple regression analysis with consideration for demographic factors such as age, sex, smoking, and methotrexate treatment. Serum LBP levels, fecal LPS levels, total bacteria counts, serum anti-LPS from Porphyromonas gingivalis (Pg-LPS) IgG antibody levels, and serum anti-Pg-LPS IgA antibody levels were selected for multiple regression analysis using Spearman's correlation analysis. Serum LBP levels were correlated with disease biomarker levels, such as erythrocyte sedimentation rate (p < 0.001), C-reactive protein (p < 0.001), matrix metalloproteinase-3 (p < 0.001), and IL-6 (p = 0.001), and were inversely correlated with hemoglobin (p = 0.005). Anti-Pg-LPS IgG antibody levels were inversely correlated with activity indices such as patient global assessments using visual analogue scale (VAS) (p = 0.002) and painVAS (p < 0.001). Total bacteria counts were correlated with ENC (p < 0.001), and inversely correlated with serum LPS (p < 0.001) and anti-Pg-LPS IgA antibody levels (p < 0.001). These results suggest that substances from oral and gut microbiota may influence disease activity in RA patients.
34514750 Effective viral vector response to SARS-CoV-2 booster vaccination in a patient with rheuma 2022 Mar Managing patients with rheumatic disease during the COVID‐19 pandemic has posed a unique challenge. Immunosuppressed patients are at an increased risk for developing severe COVID‐19 and may not derive full protection from the vaccine (1‐5). Thus, it is paramount we develop strategies whereby rheumatic disease patients can be protected from the pandemic virus and its variants.
34757601 A Review of the Totality of Evidence for the Development and Approval of ABP 710 (AVSOLA) 2022 Jan ABP 710 (AVSOLA(®)) is a biosimilar to infliximab reference product (RP), a monoclonal antibody targeting tumor necrosis factor alpha (TNFα). It is approved in the USA and Canada for all the same indications as infliximab RP. Approval of ABP 710 was based on the totality of evidence (TOE) generated using a stepwise approach to assess its similarity with infliximab RP with regard to analytical (structural and functional) characteristics, pharmacokinetic parameters, and clinical efficacy and safety. ABP 710 was shown to be analytically similar to infliximab RP including in amino acid sequence, primary peptide structure, and glycan mapping and purity. ABP 710 was also demonstrated to be similar to infliximab RP with regard to functional characterization including in vitro binding, effector functions, and signaling pathways important for the mechanisms of action for clinical efficacy in multiple indications of immune-mediated inflammatory disorders including inflammatory bowel disease (IBD), especially binding to both soluble and membrane-bound TNFα. Pharmacokinetic similarity of ABP 710 with infliximab RP was demonstrated in healthy volunteers following a single 5 mg/kg intravenous dose. Comparative clinical efficacy of ABP 710 with infliximab RP was demonstrated in patients with rheumatoid arthritis. Safety and immunogenicity were also demonstrated to be similar for both ABP 710 and the RP. Overall, the TOE supported the conclusion that ABP 710 is highly similar to infliximab RP and supported scientific justification for extrapolation to all approved indications of infliximab RP, including IBD.
35335254 Therapeutic Potential of Highly Selective A(3) Adenosine Receptor Ligands in the Central a 2022 Mar 15 Ligands of the G(i) protein-coupled adenosine A(3) receptor (A(3)R) are receiving increasing interest as attractive therapeutic tools for the treatment of a number of pathological conditions of the central and peripheral nervous systems (CNS and PNS, respectively). Their safe pharmacological profiles emerging from clinical trials on different pathologies (e.g., rheumatoid arthritis, psoriasis and fatty liver diseases) confer a realistic translational potential to these compounds, thus encouraging the investigation of highly selective agonists and antagonists of A(3)R. The present review summarizes information on the effect of latest-generation A(3)R ligands, not yet available in commerce, obtained by using different in vitro and in vivo models of various PNS- or CNS-related disorders. This review places particular focus on brain ischemia insults and colitis, where the prototypical A(3)R agonist, Cl-IB-MECA, and antagonist, MRS1523, have been used in research studies as reference compounds to explore the effects of latest-generation ligands on this receptor. The advantages and weaknesses of these compounds in terms of therapeutic potential are discussed.
33853492 Patients' perspectives of rheumatoid arthritis treatment: a questionnaire survey for the 2 2022 Feb 28 OBJECTIVES: This study aimed to evaluate patients' opinions regarding their rheumatoid arthritis (RA) therapy and to reflect the patients' perspectives in the 2020 update of the Japan College of Rheumatology clinical practice guidelines. METHODS: A self-administered questionnaire was mailed to 1600 members of the Japan Rheumatology Friendship Association, who were randomly selected by age and prefecture. RESULTS: A total of 1156 patients returned the questionnaire (response rate, 72.3%; mean age, 63.0 ± 11.9 years). Those who reported having discussed their treatment goals with their doctors (450 respondents, 38.9%) were more likely to be satisfied with their current medical care (odds ratio, 7.13; 95% CI 4.72-10.8) compared with those who had not discussed their goals nor had them explained (287 respondents, 24.8%). The benefits exceeded the adverse effects for all pharmacotherapy (methotrexate, corticosteroids, conventional synthetic antirheumatic drugs, biological agents, Janus kinase inhibitor, and anti-RANKL antibodies). However, while 74.2% of the respondents using biological agents perceived that 'the favorable aspects outweighed the unfavorable aspects,' most of those taking anti-RANKL antibodies (69.2%) felt uncertain. CONCLUSIONS: The questionnaire successfully collected information regarding patients' perceptions regarding their therapy. Further implementation of treat-to-target is necessary in Japan to improve patient satisfaction.
32700608 Patient-ready syringes containing 25 mg/mL methotrexate can be kept at temperature rangi 2022 Mar BACKGROUND: Methotrexate (MTX) is a mainstay drug in the treatment of psoriatic and rheumatologic conditions. Subcutaneous MTX has become a feasible treatment alternative with the development of prefilled syringes or autoinjectors containing MTX solution that can be self-administered by the patient at home. However, MTX prefilled auto-injector pens are still not available in some countries. OBJECTIVE: This study aimed to investigate the stability and sterility of 25 mg/mL MTX solution in a disposable plastic syringe over a 12-week period under light protection at temperatures of 4 °C, 25 °C, and 37 °C. METHODS: This study was conducted during November 2019 to February 2020 at the Faculty of Medicine Siriraj Hospital, Mahidol University. Stability was evaluated using ultra-high-performance liquid chromatography technique, and sterility was assessed by cultures for bacterial and fungal contamination. RESULTS: Our results revealed that patient-ready syringes containing 25 mg/mL MTX solution can be prepared in advance and kept for up to 12 weeks under light protection, and they can be kept at temperatures ranging from 4 to 37 °C. CONCLUSION: This system for delivering MTX to patients that are refractory to or intolerant of oral MTX via a self-administered pre-filled syringe is both efficient and easy to implement in care settings where commercially alternatives are not yet available.
35455985 How Pyroptosis Contributes to Inflammation and Fibroblast-Macrophage Cross-Talk in Rheumat 2022 Apr 12 About thirty years ago, a new form of pro-inflammatory lytic cell death was observed and termed pyroptosis. Only in 2015, gasdermins were defined as molecules that create pores at the plasma membrane and drive pyroptosis. Today, we know that gasdermin-mediated death is an important antimicrobial defence mechanism in bacteria, yeast and mammals as it destroys the intracellular niche for pathogen replication. However, excessive and uncontrolled cell death also contributes to immunopathology in several chronic inflammatory diseases, including arthritis. In this review, we discuss recent findings where pyroptosis contributes to tissue damage and inflammation with a main focus on injury-induced and autoimmune arthritis. We also review novel functions and regulatory mechanisms of the pyroptotic executors gasdermins. Finally, we discuss possible models of how pyroptosis may contribute to the cross-talk between fibroblast and macrophages, and also how this cross-talk may regulate inflammation by modulating inflammasome activation and pyroptosis induction.
35588430 Multi-locus SNP analyses of interleukin 1 receptor associated kinases 2 gene polymorphisms 2022 BACKGROUND: The genetic polymorphisms (rs708035, rs3844283) of Interleukin-1 receptor associated kinases 2 (IRAK2) is involved in the NFκB regulatory pathway. The frequencies of IRAK2 gene are unknown in Pakistani population. Therefore, the study was designed to examine the association of targeted single nucleotide polymorphism(s) in IRAK2 gene of RA patients. METHODOLOGY: The study participants were selected by ACR/EULAR 2010 standards. After ethical approval, the blood samples of patients and healthy controls were collected for the extraction of DNA followed by the amplification of targeted polymorphism(s) via Tetra-primer Amplification Refractory Mutation System (T-ARMS PCR). Desired products were observed via agarose gel electrophoresis. RESULTS: The allele frequency of wild type A and C is frequent among patients and mutant T and G is frequent among controls. The rs708035 showed significant protective association while rs3844283 was found to be associated with risk of RA. Genetic model associations were applied to determine the role of genotypes. In combination analyses of alleles revealed AC haplotype was found to be associated with risk and TG provide protection against RA. Moreover, targeted SNPs were found to be in 61% Linkage Disequilibrium among the targeted population. CONCLUSIONS: Current study revealed the protective and risk association of targeted SNPs (rs708035, rs3844283). Study might be beneficial as it provides baseline data regarding targeted SNPs and their role in the disease progression. This could be served as potential biomarker for diagnostic purpose and effectively utilized in precision medicine approach.
34920930 Refractory CIDP successfully treated with autologous haematopoietic stem cell transplantat 2022 Jan Autologous haematopoietic stem cell transplantation is an emerging treatment option in refractory chronic inflammatory demyelinating polyradiculoneuropathy. We describe a case of a 46-year-old male, with history of IgG/lambda monoclonal gammopathy, who was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy at 27 years of age. After an initial 10-year period of corticotherapy response, the patient experienced severe relapses and disease progression, evolving to a refractory state. First-line and escalating treatment could not achieve clinical stabilization, leading to severe disability. Pre-treatment with ibrutinib was initiated and autologous haematopoietic stem cell transplantation was performed without significant complications. Marked clinical improvement was observed in the following months, both subjective and objective. A significant proportion of the patients who respond to the first-line immunosuppressive therapy eventually become treatment-refractory. Autologous haematopoietic stem cell transplantation may be a treatment option, offering long-term remission with an overall acceptable side effect and risk profile.
35469829 Traditional processing, uses, phytochemistry, pharmacology and toxicology of Aconitum sino 2022 Jul 15 ETHNOPHARMACOLOGICAL RELEVANCE: As a folk medicine, Aconitum sinomontanum Nakai (Ranunculaceae) a perennial herbaceous flowering plant, is a widely used traditional Chinese medicine. Its rhizomes and roots are known as 'Gaowutou' in China, and it has been traditionally used for the treatment of rheumatoid arthritis, painful swelling of joints, bruises and injuries and has been known to grow well in regions of high altitude such as Gansu, Tibet etc. THE AIM OF THE REVIEW: This systematic review the comprehensive knowledge of the A. sinomontanum, including its traditional processing and uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and its use in clinical settings to emphasize the benefits of this species. We also discuss expectations for prospective research and implementation of this herb. This work lays a solid foundation for further development of A. sinomontanum. MATERIALS AND METHOD: Information on the studies of A. sinomontanum was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters dissertation. RESULTS: As a member of the Ranunculaceae family, A. sinomontanum possesses its up-and-coming biological characteristics. It is widely reported for treating rheumatoid arthritis, painful swelling of joints, bruises and injuries. Currently, over 71 phytochemical ingredients have been obtained and identified from different parts of A. sinomontanum. Among them, alkaloids, flavonoids, steroids, glycosides are the major bioactive constituents. Activities such as antinociceptive, anti-inflammatory, antitumor, antiarrhythmic, local anesthetic, antipyretic, antimicrobial, insecticidal and others have been corroborated in vivo and in vitro. These properties are attributed to different alkaloids. In addition, many of the active ingredients, such as lappaconitine, ranaconitine and total alkaloids have been used as quality markers. CONCLUSION: This work contributes to update the ethnopharmacological uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and clinical settings information for A. sinomontanum, which provide basic information to help better understand the pharmacological and toxicological activities of A. sinomontanum in human. However, further in-depth studies are needed to determine the medical uses of this herb and its chemical constituents, pharmacological activities, clinical applications and toxicology.
35020859 Evaluation of a fit-for-purpose assay to monitor antigen-specific functional CD4+ T-cell s 2022 Jan 28 Antigen-specific T cells can serve as a response biomarker in non-clinical or clinical immunotherapy studies in autoimmune disease. There are protocols with optimized multimer staining methods to detect peptide (p)MHCII+ CD4+ T cells, and some qualified and validated protocols for pMHCI+ CD8+ T cells. However, no protocol is fully or partially qualified to enumerate and characterize antigen-specific pMHCII+ CD4+ T cells from patient samples. Implementing such an assay requires a desired level of specificity and precision, in terms of assay repeatability and reproducibility. In transgenic type II collagen (CII)-immunized HLA-DR1/DR4 humanized mouse models of collagen-induced arthritis (CIA), CII259-273-specific T cells dominantly expand. Therefore antigen-specific T cells recognizing this epitope presented by rheumatoid arthritis (RA)-associated risk HLA-DR allomorphs are of interest to understand disease progression and responses to immunotherapy in RA patients. Using HLA-DRB1∗04:01 or ∗01:01-collagen type II (CII)259-273 tetramers, we evaluated parameters influencing precision and reproducibility of an optimized flow cytometry-based method for antigen-specific CD4+ T cells and eight specific subpopulations with and without tetramer positivity. We evaluated specificity, precision, and reproducibility for research environments and non-regulated laboratories. The assay has excellent overall precision with %CV<25% for intra-assay repeatability, inter-analyst precision, and inter-assay reproducibility. The precision of the assay correlated negatively with the cell viability after thawing, indicating that post-thaw viability is a critical parameter for reproducibility. This assay is suitable for longitudinal analysis of treatment response and disease activity outcome in RA patients, and adaptable for translational or immunotherapy clinical trial settings.
35389123 The anti-angiogenesis mechanism of Geniposide on rheumatoid arthritis is related to the re 2022 Jun Rheumatoid arthritis (RA) is a systemic immune disease characterized by joint inflammation and pannus. The nascent pannus contributes to synovial hyperplasia, cartilage, and tissue damage in RA. This study aims to explore the therapeutic effect and potential mechanism of Geniposide (GE) on RA angiogenesis, involving the participation of phosphate and tension homology deleted on chromosome ten (PTEN) and downstream pathways. Clinical manifestations, synovial pathomorphology, microvessel density, and the level of angiogenesis-related factors were used to evaluate the therapeutic effect of GE on adjuvant-induced arthritis (AA) rats. The proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) indicate the degree of angiogenesis in vitro. Lentivirus over-expression of PTEN was employed to elucidate the potential mechanism. The results showed that GE improved the degree of arthritis and angiogenesis in AA rats. The expression of PTEN was decreased significantly in vivo and in vitro, and over-expression of PTEN improved the biological function of HUVECs to inhibit angiogenesis. GE inhibited the proliferation, migration, and tubule formation of HUVECs and plays an anti-angiogenesis role in vitro. Mechanism study showed that PTEN expression was increased and p-PI3K and p-Akt expression was decreased with GE treatment. It suggests that GE up-regulated the expression of PTEN and inhibited the activation of PI3K-Akt signal, which plays a role in inhibiting angiogenesis in RA in vivo and in vitro.
35105713 COVID-19 Hospitalizations, Intensive Care Unit Stays, Ventilation, and Death Among Patient 2022 May OBJECTIVE: To investigate coronavirus disease 2019 (COVID-19) hospitalization risk in patients with immune-mediated inflammatory diseases (IMIDs) compared with matched non-IMID comparators from the general population. METHODS: We conducted a population-based, matched cohort study using health administrative data from January to July 2020 in Ontario, Canada. Cohorts for each of the following IMIDs were assembled: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), ankylosing spondylitis, systemic autoimmune rheumatic diseases (SARDs), multiple sclerosis (MS), iritis, inflammatory bowel disease, polymyalgia rheumatica, and vasculitis. Each patient was matched with 5 non-IMID comparators based on sociodemographic factors. We compared the cumulative incidence of hospitalizations for COVID-19 and their outcomes between IMID and non-IMID patients. RESULTS: A total of 493,499 patients with IMID (417 hospitalizations) and 2,466,946 non-IMID comparators (1519 hospitalizations) were assessed. The odds of being hospitalized for COVID-19 were significantly higher in patients with IMIDs compared with their matched non-IMID comparators (matched unadjusted odds ratio [OR] 1.37, adjusted OR 1.23). Significantly higher risk of hospitalizations was found in patients with iritis (OR 1.46), MS (OR 1.83), PsA (OR 2.20), RA (OR 1.42), SARDs (OR 1.47), and vasculitis (OR 2.07). COVID-19 hospitalizations were associated with older age, male sex, long-term care residence, multimorbidity, and lower income. The odds of complicated hospitalizations were 21% higher among all IMID vs matched non-IMID patients, but this association was attenuated after adjusting for demographic factors and comorbidities. CONCLUSION: Patients with IMIDs were at higher risk of being hospitalized with COVID-19. This risk was explained in part by their comorbidities.
35527996 High Follicle-Stimulating Hormone Level Associated With Risk of Rheumatoid Arthritis and D 2022 BACKGROUND: The prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity. METHODS: In total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups. RESULTS: Lower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls (57.58 ± 15.94 vs. 43.11 ± 19.46, p=0.025). Even after adjusting for age (OR: 1.071; 95%CI: 1.006-1.139; p = 0.031), luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p<0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients (r = 0.432, p =0.008). CONCLUSION: High FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA.
32279586 Off-Label studies on anakinra in dermatology: a review. 2022 Feb PURPOSE: Anakinra (Kineret(®)) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease (NOMID). It has been used off-label for a variety of dermatologic conditions. A review of the available studies and cases of these off-label uses would be valuable to the dermatologist considering alternative treatments for these oftentimes poorly studied conditions. MATERIALS AND METHODS: The PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term 'anakinra.' Results were manually screened to identify published data on off-label uses of anakinra in dermatologic conditions and systemic conditions with prominent dermatologic manifestations. RESULTS: Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome. Case reports and case series data are available for numerous other dermatologic conditions. CONCLUSION: Anakinra is a potential option for patients with certain difficult-to-treat dermatologic diseases, given its relatively benign adverse effect profile and its effectiveness in a wide array of conditions. Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role.
34493490 Analysing cord blood levels of TNF inhibitors to validate the EULAR points to consider for 2022 Mar BACKGROUND: To minimise placental transfer of tumour necrosis factor inhibitors (TNFi), the European League Against Rheumatism (EULAR) created points to consider (PtC) for the use of TNFi during pregnancy. We are the first to validate the EULAR-PtC by analysing TNFi concentrations in cord blood. METHODS: Patients were derived from the Preconceptional Counselling in Active Rheumatoid Arthritis Study. TNFi was stopped at the time points recommended by the EULAR. Maternal blood and cord blood were collected and analysed for the concentration of TNFi. RESULTS: 111 patients were eligible for the analysis. Median stop time points were gestational age (GA) 37.0 weeks for certolizumab pegol, GA 25.0 weeks for etanercept, GA 19.0 weeks for adalimumab and GA 18.4 weeks for infliximab. Certolizumab pegol (n=68) was detectable in 5.9% of cord blood samples, with a median concentration of 0.3 µg/mL (IQR: 0.2-1.3) and a median cord/maternal concentration ratio of 0.010. Etanercept (n=30) was not detected in any cord blood samples. Adalimumab (n=25) was detectable in 48.0% of cord blood samples, with a median concentration of 0.5 µg/mL (IQR: 0.2-0.7) and a median concentration ratio of 0.062 (IQR: 0.018-0.15). Infliximab (n=14) was detectable in 57.1% of cord blood samples, with a median concentration of 0.4 µg/mL (IQR: 0.1-1.2) and a median concentration ratio of 0.012 (IQR: 0.006-0.081). CONCLUSION: Compliance with the EULAR-PtC results in absence or low levels of TNFi in cord blood.
35304639 Study of Plasma Anti-CD26 Autoantibody Levels in a Cohort of Treatment-Naïve Early Arthri 2022 Mar 18 In rheumatoid arthritis (RA), the identification of biomarkers to adjust treatment intensity and to correctly diagnose the disease in early stages still constitutes a challenge and, as such, novel biomarkers are needed. We proposed that autoantibodies (aAbs) against CD26 (DPP4) might have both etiological importance and clinical value. Here, we perform a prospective study of the potential diagnostic power of Anti-CD26 aAbs through their quantification in plasmas from 106 treatment-naïve early and undifferentiated AR. Clinical antibodies, Anti-CD26 aAbs, and other disease-related biomarkers were measured in plasmas obtained in the first visit from patients, which were later classified as RA and non-RA according to the American College of Rheumatology criteria. Two different isotype signatures were found among ten groups of patients, one for Anti-CD26 IgA and other for Anti-CD26 IgG and IgM isotypes, both converging in patients with arthritis (RA and Unresolved Undifferentiated Arthritis: UUA), who present elevated levels of all three isotypes. The four UUA patients, unresolved after two years, were ACPA and rheumatic factor (RF) negatives. In the whole cohort, 51.3% of ACPA/RF seronegatives were Anti-CD26 positives, and a similar frequency was observed in the seropositive RA patients. Only weak associations of the three isotypes with ESR, CRP and disease activity parameters were observed. Anti-CD26 aAbs are present in treatment-naïve early arthritis patients, including ACPA and RF seronegative individuals, suggestive of a potential pathogenic and/or biomarker role of Anti-CD26 aAbs in the development of rheumatic diseases.