scholarly journals Chronic pain and central sensitization in immuno-inflammatory rheumatic diseases: pathogenesis, clinical manifestations, the possibility of using targeted disease modifying antirheumatic drugs

2019 ◽  
Vol 57 (2) ◽  
pp. 197-209 ◽  
Author(s):  
A. E. Karateev ◽  
E. L. Nasonov
Keyword(s):  
Chronic Pain ◽  
Rheumatic Diseases ◽  
Central Sensitization ◽  
Effective Means ◽  
Clinical Manifestations ◽  
Inflammatory Rheumatic Diseases ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Nociceptive Neurons ◽  
Disease Modifying

Chronic pain is one of the main manifestations of immuno-inflammatory rheumatic diseases (IIRD), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), which determines the severity of suffering, reduced quality of life and disability of patients. Unfortunately, the use of synthetic and biological disease modifying antirheumatic drugs, as well as non-steroidal anti-inflammatory drugs does not always provide sufficient control of pain in IIRD, even when it is possible to achieve a significant reduction in inflammatory activity. The reason for this is the complex mechanism of chronic pain. It includes not onlystimulation of pain receptors caused by damage of the elements of the musculoskeletal system, but also a change in the perception of pain associated with the phenomenon of central sensitization (CS). CS is characterized by a significant and persistent increase in the sensitivity of nociceptive neurons to pain and nonpain stimuli. One of the main theories of the CS development consider this phenomenon as an inflammatory reaction of the neuronenvironmentthe activation of astrocytes and microglial cells, local hyperproduction of cytokines, inflammatory mediators and neurotrophic factors. Factors contributing to the development of CS in IIRD are obesity, depression and anxiety, damage of the somatosensory system, insufficient relief of pain in the onset of the disease. Clinical manifestations of CS in IIRD is hyperalgesia, allodinia, «expanded pain» and secondary fibromyalgia. An important role in the development of chronic pain and CS plays the intracellular inflammatory pathway JAK-STAT. Therefore, JAK inhibitors, such as tofacitinib, used in RA and PsA, can also be considered as an effective means of controlling chronic pain in these diseases.

scholarly journals Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases

2020 ◽  
Vol 79 (11) ◽  
pp. 1393-1399 ◽  
Author(s):  
Dalifer D Freites Nuñez ◽  
Leticia Leon ◽  
Arkaitz Mucientes ◽  
Luis Rodriguez-Rodriguez ◽  
Judit Font Urgelles ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hospital Admission ◽  
Rheumatic Diseases ◽  
Hospital Admissions ◽  
Tertiary Hospital ◽  
Inflammatory Rheumatic Diseases ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Multivariable Logistic Regression Model ◽  
Disease Modifying

ObjectivesTo describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19.MethodsAn observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission.ResultsThe study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3–10) days. The median length of stay was 9 (6–14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model.ConclusionOur results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.

scholarly journals Hospital admissions in inflammatory rheumatic diseases during the peak of COVID-19 pandemic: incidence and role of disease-modifying agents

2021 ◽  
Vol 13 ◽  
pp. 1759720X2096269
Author(s):  
Benjamin Fernandez-Gutierrez ◽  
Leticia Leon ◽  
Alfredo Madrid ◽  
Luis Rodriguez-Rodriguez ◽  
Dalifer Freites ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Rheumatic Diseases ◽  
Hospital Admissions ◽  
Statistical Significance ◽  
Severe Infection ◽  
Inflammatory Rheumatic Diseases ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

Aims: In this pandemic, it is essential for rheumatologists and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRDs). We wanted to assess the role of targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. Methods: An observational longitudinal study was conducted during the epidemic peak in Madrid (1 March to 15 April 2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19 was expressed per 1000 patient-months. Cox multiple regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR of hospital admission related to COVID-19. Results: A total of 3951 IRD patients were included (5896 patient-months). Methotrexate was the csDMARD most used. Eight hundred and two patients were on ts/bDMARDs, mainly anti-TNF agents, and Rtx. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 (95% confidence interval: 7–11.9). In the multivariate analysis, older, male, comorbidities, and specific systemic autoimmune conditions (Sjögren, polychondritis, Raynaud, and mixed connective tissue disease) had more risk of hospital admissions. Exposition to ts/bDMARDs did not achieve statistical significance. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. Conclusion: This study provides additional evidence in IRD patients regarding susceptibility to moderate–severe infection related to COVID-19.

scholarly journals Biological agents for rheumatic diseases in the outbreak of COVID-19: friend or foe?

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001439
Author(s):  
Cristiana Sieiro Santos ◽  
Xenia Cásas Férnandez ◽  
Clara Moriano Morales ◽  
Elvira Díez Álvarez ◽  
Carolina Álvarez Castro ◽  
...  
Keyword(s):  
General Population ◽  
Rheumatic Disease ◽  
Infection Rate ◽  
Rheumatic Diseases ◽  
Hospital Care ◽  
Biological Agents ◽  
Inflammatory Rheumatic Diseases ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

BackgroundThe recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressed patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biological agents may suppose a risk or protection against SARS-CoV-2 infection; however, it has been suggested that severe respiratory forms of COVID-19 occur as a result of exacerbated inflammation status and cytokine production. This prompted the use of interleukin 6 (IL-6) (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV-2.ObjectivesTo estimate COVID-19 infection rate in patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) for inflammatory rheumatic diseases (RMD), determine the influence of biological agents treatment as risk or protective factors and study the prognosis of patients with rheumatic diseases receiving biological agents compared to the general population in a third-level hospital setting in León, Spain.MethodsWe performed a retrospective observational study including patients seen at our rheumatology department who received bDMARDs for rheumatic diseases between December 1st 2019 and December 1st 2020, and analysed COVID-19 infection rate. All patients who attended our rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biological agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biological agent, duration of treatment, mean dose of glucocorticoids and need for intensive care unit . We performed an univariate and multivariate logistic regression models to assess risk factors of COVID-19 infection.ResultsThere were a total of 4464 patients with COVID-19 requiring hospitalisation. 40 patients out of a total of 820 patients with rheumatic diseases (4.8%) receiving bDMARDs contracted COVID-19 and 4 required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 3.6%, and it was 0.89% among the group with underlying rheumatic diseases. 90% of patients receiving bDMARDS with COVID-19 did not require hospitalisation. Out of the 4464 patients, 869 patients died, 2 of which received treatment with biological agents. Patients with rheumatic diseases who tested positive for COVID-19 were older (female: median age 60.8 IQR 46-74; male: median age 61.9 IQR 52-70.3) than those who were negative for COVID-19 (female: median age 58.3 IQR 48-69; male: median age 56.2 IQR 47-66), more likely to have hypertension (45% vs 26%, OR 2.25 (CI 1.18-4.27),p 0.02), cardiovascular disease (23 % vs 9.6%, OR 2.73 (1.25-5.95), p 0.02), be smokers (13% vs 4.6%, OR 2.95 (CI 1.09-7.98), p 0.04), receiving treatment with rituximab (20% vs 8%, 2.28 (CI 1.24-6.32), p 0.02) and a higher dose of glucocorticoids (OR 2.5 (1.3-10.33, p 0.02) and were less likely to be receiving treatment with IL-6 inhibitors (2.5% vs 14%, OR 0.16, (CI 0.10-0.97, p 0.03). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bDMARD proportions. IL-1 inhibitors, IL-6 inhibitors, JAK inhibitors and belimumab-treated patients showed the lowest incidence of COVID-19 among adult patients with rheumatic diseases. We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative.ConclusionsOverall, the use of biological disease-modifying antirheumatic drugs (bDMARDs) does not associate with severe manifestations of COVID-19. Patients with rheumatic disease diagnosed with COVID-19 were more likely to be receiving a higher dose of glucocorticoids and treatment with rituximab. IL-6 inhibitors may have a protective effect.

Management of anti-HBc-positive patients with rheumatic diseases treated with disease-modifying antirheumatic drugs—a single-center analysis of 2054 patients

2018 ◽  
Vol 37 (11) ◽  
pp. 2963-2970 ◽  
Author(s):  
Eva C. Schwaneck ◽  
Manuel Krone ◽  
Sonja Kreissl-Kemmer ◽  
Benedikt Weißbrich ◽  
Johannes Weiss ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Single Center ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

scholarly journals Comparison of clinical manifestations of rheumatoid arthritis in patients with moderate or high disease activity depending on the presence or absence of symptoms of neuropathic pain

2021 ◽  
Vol 15 (6) ◽  
pp. 13-18
Author(s):  
E. Yu. Polishchuk ◽  
E. S. Filatova ◽  
A. E. Karateev ◽  
V. N. Amirdzhanova ◽  
V. A. Nesterenko
Keyword(s):  
Rheumatoid Arthritis ◽  
Neuropathic Pain ◽  
Disease Activity ◽  
Pain Intensity ◽  
Clinical Manifestations ◽  
High Disease Activity ◽  
Control Group ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

Objective: to study the effect of neuropathic pain symptoms (SNP) on the clinical manifestations of rheumatoid arthritis (RA) in patients with moderate or high disease activity.Patients and methods. The 1st (main) group included 58 RA patients (84.5% of women, age 53.0±11.9 years), in whom SNP were identified using the DN4 (≥4) and PainDETECT (≥13) questionnaires. The 2nd (control) group included 43 patients with RA (79.1% women, age 48.8±14.4 years) who did not have SNP (DN4 ≤4 and PainDETECT ≤13). All patients received disease-modifying antirheumatic drugs (mainly methotrexate and leflunomide), 20% – biologic disease-modifying antirheumatic drugs. We compared groups 1 and 2 for RA activity (DAS28, CDAI, SDAI), pain intensity on a visual analogue scale (VAS, 0–100 mm), functional impairment (HAQ), patient global assessment (PGA, VAS), number of painful and swollen joints, quality of life (EQ-5D), signs of anxiety and depression (HADS), CRP level.Results and discussion. The RA activity in patients of the 1st and 2nd groups did not differ statistically significantly. Patients of the 1st group showed significantly higher indicators of the severity of pain, PGA and anxiety than patients of the control group: 71.0±12.5 and 54.7±17.5 mm, respectively (p<0.001); 61.0±13.1 and 53.7±15.3 mm (p=0.045); 62.1 and 28.6% (HADS ≥7; p<0.001), respectively.Conclusion. SNP are associated with higher rates of pain intensity, PGA, and anxiety in RA patients with moderate to high disease activity.

Biologic Disease-modifying Antirheumatic Drug (bDMARD)-induced Neutropenia: A Registry from a Retrospective Cohort of Patients with Rheumatic Diseases Treated with 3 Classes of Intravenous bDMARD

2017 ◽  
Vol 44 (6) ◽  
pp. 844-849 ◽  
Author(s):  
Francisco Espinoza ◽  
Pierre Le Blay ◽  
Bernard Combe
Keyword(s):  
Rheumatic Diseases ◽  
Retrospective Cohort ◽  
Concomitant Treatment ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Drug Survival ◽  
History Of ◽  
Severe Infections ◽  
Risks Factors ◽  
Disease Modifying

Objective.To examine the rate, risks factors, and consequences of neutropenia induced by intravenous (IV) biologic disease-modifying antirheumatic drugs (bDMARD).Methods.We conducted a retrospective cohort study in 499 patients with rheumatic diseases treated by IV abatacept (ABA), infliximab (IFX), or tocilizumab (TCZ).Results.Rheumatoid arthritis (RA) was the most frequent diagnosis (72%). Fifty-two patients (10.4%) experienced at least 1 episode of neutropenia. No episodes of grade 4 neutropenia were documented. TCZ was more frequently related to neutropenia than ABA or IFX (18.6% vs 3.8% and 2.8%, respectively, p < 0.001). The following factors were identified as predictors of experiencing neutropenia with IV bDMARD: history of neutropenia with methotrexate (MTX; synthetic DMARD; OR 1.56, 95% CI 1.17–7.14), concomitant treatment by MTX (OR 1.21, 95% CI 1.01–2.64), and TCZ treatment (OR 2.72, 95% CI 1.53–9.05). Patients experiencing a TCZ-induced neutropenia did not show a higher risk of severe infections; however, this group had a shorter drug survival (9 mos vs 20 mos, p < 0.02) compared with TCZ patients without neutropenia.Conclusion.Among 3 different classes of IV bDMARD, TCZ is associated with the higher risk of neutropenia. No increased frequency of infection episodes was documented in this group.

scholarly journals Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e021447 ◽  
Author(s):  
Ettore Silvagni ◽  
Alessandra Bortoluzzi ◽  
Greta Carrara ◽  
Anna Zanetti ◽  
Marcello Govoni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Record Linkage ◽  
Disease Duration ◽  
Retention Rate ◽  
First Line ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Risk Of Failure ◽  
Disease Modifying

ObjectiveThese analyses aim to comparatively evaluate the persistence on treatment of different biological disease-modifying antirheumatic drugs (bDMARDs) when administered in monotherapy compared with combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA) patients receiving first-line biologics.DesignThis is a retrospective observational study on Administrative Healthcare Databases.MethodsData were extracted from healthcare databases of the Lombardy Region, Italy (2004–2013), as a part of the RECord-linkage On Rheumatic Diseases study, on behalf of the Italian Society for Rheumatology. Analyses included patients with RA starting first-line approved course of bDMARDs and evaluated drug survival by using Cox proportional hazard models. Results are presented as HRs and 95% CI, crude and adjusted for prespecified confounders (age, sex, disease duration, Charlson Comorbidity Index (CCI), previous infections, use of concomitant glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs)).Results4478 patients with RA were included (17.84% monotherapy). Etanercept, adalimumab and infliximab were the most prescribed first-line biologics. bDMARD monotherapy was associated with longer disease duration, higher CCI, lower glucocorticoids and NSAIDs use. Compared with monotherapy, combination associated with a lower risk of failure (adjusted HR 0.79, 95% CI 0.72 to 0.88). Among monotherapies, considering etanercept as reference, adalimumab (1.28, 95% CI 1.03 to 1.59) and infliximab (2.41, 95% CI 1.85 to 3.15) had higher risk of failure. Concomitant methotrexate (0.78, 95% CI 0.70 to 0.87), leflunomide (0.80, 95% CI 0.65 to 0.98) or csDMARD combinations (0.77, 95% CI 0.68 to 0.87) reduced the risk of bDMARD withdrawal.ConclusionAdalimumab and infliximab monotherapies show lower retention rate compared with etanercept. The relatively small number of therapeutic courses different from tumour necrosis factor (TNF) inhibitors makes more difficult to achieve conclusive results with other biologics. Concomitant methotrexate, leflunomide and csDMARDs combination associate with longer survival on bDMARD. Our data confirm the effectiveness of the current practices in the choice of etanercept as first-line anti-TNF monotherapy and strengthen the currently recommended use of bDMARDs in combination with csDMARDs.

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