Effects Of Disease-modifying Antirheumatic Drugs Research Articles

The Impact of Pre-Existing Autoimmune Disease on the Safety and Efficacy of CAR T-Cell Therapy for Non-Hodgkin Lymphoma

Introduction: Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of non-Hodgkin lymphoma (NHL). Despite having an increased risk of NHL, patients with pre-existing autoimmune disease (AID) were excluded from pivotal CAR-T trials due to concerns that CAR-T may exacerbate AID. As a result, there are limited data on the safety and efficacy of CAR-T for NHL in patients with AID. Interestingly, there is also growing evidence that CAR-T can be therapeutically effective for AID, such as in the treatment of systemic lupus erythematosus (SLE). As CAR-T utilization for NHL increases, it is essential to characterize the safety and efficacy of this potentially curative therapy in patients with AID. This study aimed to evaluate the impact of AID on outcomes in patients treated with commercial CD19-targeted CAR-T for NHL. Methods: Following Institutional Review Board approval, we conducted a retrospective analysis of all patients who were treated with commercial CD19-targeted CAR-T for NHL and had a pre-existing AID across the Mayo Clinic Enterprise (Arizona, Florida, and Minnesota) between January 2018 and May 2023. Variables collected included age, gender, NHL type, AID type, and CAR-T product. Efficacy outcomes, including response rates at 6 and 12 months after CAR-T, were collected. Toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), were collected and analyzed. Our chart review for AID included SLE, sarcoidosis, ulcerative colitis, celiac disease, pernicious anemia, Crohn's disease, psoriasis, Sjogren's syndrome, hypothyroidism (Hashimoto's disease), hyperthyroidism (Graves' disease), rheumatoid arthritis (RA), vasculitis, scleroderma, and mixed connective tissue disease (MCTD). Results: A total of 235 patients who received commercial CD19-targeted CAR-T for NHL across the Mayo Clinic Enterprise were identified (Table 1). Of these 235 patients, 27 had a pre-existing AID and 208 did not. The median age was 66 years (range 39-81) for patients with AID and 59 years (range 18-88) for patients without AID. Over half of the patients were male (59% of patients with AID and 51% of patients without AID). The most common NHL type was diffuse large B cell lymphoma (41% of patients with AID and 56% of patients without AID). Most patients received axicabtagene ciloleucel (85% of patients with AID and 84% of patients without AID). The most common AID was hypothyroidism (81%, n=22), although other conditions were also identified, including RA (11%, n=3), SLE (4%, n=1), pulmonary sarcoidosis (4%, n=1), psoriasis (4%, n=1), and MCTD (4%, n=1). Two patients had more than one AID. Median follow-up was 18 months (range 1-36) for patients with AID and 14 months (range 2-49) for patients without AID. Six months after CAR-T, the complete response (CR) rate was 77.2% and 45.1% in patients with AID and without AID, respectively (p=0.0042). Twelve months after CAR-T, the CR rate was 50% and 31.4% in patients with AID and without AID, respectively (p=0.0801). CRS of any grade occurred in 78% and 88% of patients with and without AID, respectively. ICANS of any grade occurred in 41% and 54% of patients with and without AID, respectively. Conclusion: AID did not appear to adversely impact the safety or efficacy of CAR-T for NHL. Limitations of our study include the small number of patients with AID and the fact that the most common AID was hypothyroidism. Larger studies are warranted to confirm these findings. Additional data are needed to characterize the impact of CAR-T for NHL on AID outcomes and to describe the effect of disease-modifying antirheumatic drugs on NHL outcomes after CAR-T.

Rheumatoid Arthritis and Periodontal Disease Association and Effect of Disease Modifying Anti-Rheumatic Drugs: A Narrative Review

Associations between periodontal disease (PD) and other diseases, including rheumatoid arthritis (RA), respiratory disease, and chronic kidney disease, have been reported. Patients with moderate to severe periodontitis have a high risk of suffering from RA and vice versa. This bidirectional relationship could be due to genetic (HLA-DR), dysregulation of the inflammatory response, and the role of Porphyromonas gingivalis (P. gingivalis), which stimulates anti-cyclic citrullinated peptide antibodies via citrullination. This review aims to identify associated factors that contribute to RA and PD relationship and to explore the effects of disease-modifying anti-rheumatic drugs (DMARDs) on PD. A literature search was performed using PubMed and Google Scholar to identify related articles published from the year 1990 to 2020 within the research interest using keyword combinations. Thirty-one articles that fit the research interest and address the research questions for both objectives were selected. As a result, the associated factors for RA and PD relationship, including genetic predisposition, immunoregulatory imbalance, and the role of P. gingivalis in the citrullination process as a risk factor of RA. Significant improvement was found in periodontal parameters in RA patients treated with biologic and synthetic DMARDs. This review reported common factors contributing to the RA and PD relationship and the benefits of DMARDs on periodontitis.

Evolution of monoclonal gammopathy of undetermined significance in patients treated with JAK inhibitors for rheumatic diseases: data from the MAJIK-SFR registry.

Monoclonal gammopathy of undetermined significance (MGUS) is common, but there are scarce data regarding the effect of DMARDs on this premalignant condition. We aimed to evaluate the impact of JAK inhibitors (JAKis) on MGUS when initiated for an active rheumatic disease. Patients with monoclonal abnormality prior to JAKi initiation for an active rheumatic disease were identified through the MAJIK-SFR Registry, a French multicentre prospective study. Clinical and biological data were collected using a standardized case report form. Twenty patients were identified with a mean age of 65 years and a diagnosis of RA (n = 15), PsA (n = 3), and axial SpA (n = 2). The JAKi prescribed was baricitinib (n = 9), tofacitinib (n = 6) or upadacitinib (n = 5), with a mean duration of 15.5 months. Seventeen patients had individualized serum monoclonal protein (IgG kappa n = 9; IgG lambda n = 4; IgM kappa n = 3; IgA lambda n = 1) ranging from 0.16 to 2.3 g/dl, and three patients did not have an initial measurable spike but they had a positive serum immunofixation. With a follow-up of 4-28 months, the serum monoclonal protein level decreased in 8 of 17 patients (47%), remained stable in 8 patients (47%) and increased in 1 patient (6%). The maximal decrease observed was an initial IgG kappa of 2.3 g/dl, decreasing to 0.2 g/dl at month 14. This study provides reassuring and promising data on MGUS evolution in patients treated with JAKis for rheumatic diseases, which may guide the choice of treatment in patients with both conditions.

The effect of disease-modifying antirheumatic drugs on sleep and quality of life in older patients with rheumatoid arthritis.

The sleep quality is worse in rheumatoid arthritis (RA) patients than in healthy controls and it is more difficult to achieve a satisfactory quality of life after treatment with age. Our aim is to assess the quality of life and sleep in elderly onset RA patients and to analyze the effect of disease-modifying agents on sleep and quality of life. Thirty-four older patients with RA patients and 30 healthy controls are included in the study. Sleep quality was evaluated with the Pittsburg sleep quality index and quality of life with Short Form-36. Parametric/non-parametric tests and Spearman/Pearson correlation analysis were applied for the data according to the distribution. While the rate of poor sleep quality before treatment was 67.6%, the rate was 26.5% after treatment. There was a statistically significant difference before and after treatment in terms of subjective sleep quality, sleep latency, sleep duration, sleep efficiency, and scores for sleep disturbance. The mean steroid dose and Disease Activity Score-28 were higher in patients with poor sleep quality than in patients with good sleep quality. Patients with poor sleep quality had lower mean physical function, pain, general health, social function, emotional role difficulties, and energy/vitality values than patients with good sleep quality. Both sleep and quality of life improved after treatment in older patients with RA patients. In older patients, it should be regularly evaluated in terms of sleep and quality of life and appropriate treatment should be provided.

A systematic comparison of different composite measures (DAS 28, CDAI, SDAI, and Boolean approach) for determining treatment effects on low disease activity and remission in rheumatoid arthritis.

Some composite measures for determining the treatment effects of disease-modifying antirheumatic drugs on remission and low disease activity (LDA) in rheumatoid arthritis (RA) may produce misleading results if they include an acute phase reactant (APR). To inform the choice of appropriate measure, we performed a systematic comparison of treatment effects using different composite measures. We used data generated for a systematic review of biologics in RA conducted by the Institute for Quality and Efficiency in Health Care and data from systematic reviews of newer biologics and Janus kinase (JAK) inhibitors provided by sponsors. The studies included had been conducted up to 2020 and investigated comparisons of biologics with placebo and head-to-head comparisons of biologics. Treatment effects on LDA and remission in studies investigating biologics or JAK inhibitors in RA were compared among 4 composite measures: the disease activity score 28 (DAS 28), the simplified disease activity index (SDAI), the Boolean approach (remission only), and the clinical disease activity index (CDAI)-only the latter does not include an APR. 49 placebo-controlled studies included 9 different biologics; 48 studies (16,233 patients) investigated LDA and 49 (16,338 patients) investigated remission. 11 active-controlled studies (5996 patients) investigated both LDA and remission and included 5 different head-to-head comparisons of biologics and 5 different comparisons (6 studies) of biologics with JAK inhibitors. Statistically significantly larger treatment effects were found for biologics or JAK inhibitors versus placebo or active control in 16% of pairwise comparisons of composite measures (27 of 168). Most of these larger effects were observed for composite measures with an APR, i.e. the DAS28 (19 comparisons) followed by the SDAI (n = 7). Larger effects were most frequently detected in favour of interleukin (IL)-6 inhibitors and to a lesser extent for JAK inhibitors versus treatments with different modes of action. The use of the DAS 28 and SDAI in clinical studies may generate results favouring certain treatments based on their mode of action (e.g. IL-6 inhibitors versus other biologics). To enable unbiased comparative effectiveness research, a composite measure without an APR (i.e. the CDAI) should thus be the measure of choice.

Antidiabetic effect of disease-modifying antirheumatic drugs

Leki modyfikujące przebieg choroby stanowią podstawę leczenia przewlekłych zapaleń stawów, hamują postęp choroby i mogą doprowadzić do stanu remisji. Większość z tych leków to preparaty o działaniu immunosupresyjnym oraz leki biologiczne. Pojawiają się doniesienia o dodatkowych, oprócz efektu przeciwzapalnego, działaniach tych preparatów, w tym o działaniu przeciwcukrzycowym. Celem pracy jest przedstawienie dostępnych obecnie wyników badań i obserwacji klinicznych, wskazujących na możliwość wielokierunkowego działania leków modyfikujących przebieg choroby, szczególnie efektu redukującego ryzyko rozwoju cukrzycy i zależnych od niej powikłań.

Risk of New-Onset Diabetes Mellitus Associated with Antirheumatic Drugs in Patients with Rheumatoid Arthritis: A Nationwide Population Study.

Background: This study aimed to investigate the effect of disease-modifying antirheumatic drugs (DMARDs) on diabetes mellitus (DM) development in rheumatoid arthritis (RA). Methods: This nested case–control study with a cohort of 69,779 DM-naïve adult patients with RA was conducted from 2011 to 2019 in South Korea. Cases with incident DM were identified and individually matched to randomly selected controls (1:4). DMARDs use was measured for 1 year before the index date and stratified by exposure duration. The association of each DMARD use with DM risk was estimated using conditional logistic regression adjusted for comorbidities and concomitant drug use. Results: Of the patients, 5.4% were newly diagnosed with DM. The use of statins and a higher cumulative dose of corticosteroids were associated with an increased DM risk. In a multivariable-adjusted analysis, cumulative duration of exposure (CDE) >270 days/year, hydroxychloroquine (HCQ; adjusted odds ratio [aOR], 0.76) and methotrexate (MTX; aOR, 0.81) were associated with a significant decrease in DM risk, and tacrolimus (TAC; aOR, 1.27) was associated with an increased risk. Conclusions: Long-term use of HCQ and MTX (>270 days/year) was associated with a reduction in DM incidence as opposed to TAC.

Differential cardiovascular effects of disease-modifying antirheumatic drugs in rheumatoid arthritis.

Differential cardiovascular effects of disease-modifying antirheumatic drugs in rheumatoid arthritis.

VACCINATED WITH A TWIST: BREAKTHROUGH COVID-19 IN AN IMMUNOCOMPROMISED PATIENT

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: With ongoing efforts to vaccinate the public against SARS-CoV2, there have been reports of breakthrough COVID-19 cases. We report a case of an immunocompromised patient who was infected despite being fully vaccinated. CASE PRESENTATION: 63-year-old female with COPD, rheumatoid arthritis on abatacept, prednisone, & methotrexate (MTX), and Sweet syndrome presented to the ED with acute non-exertional chest pain, palpitations, and dyspnea at rest. She denied fevers or chills but reported diarrhea and vomiting. She had no history of or exposure to COVID-19 and had completed her 2-dose mRNA SARS-CoV-2 vaccination 45 days prior. On presentation she was in respiratory distress, hypotensive, tachycardic, and tachypneic. She was saturating at 86% on room air, requiring supplemental O2. Physical exam was significant for scattered bilateral wheezes. CBC showed no leukocytosis. CRP was elevated. Lactic acid, ferritin and LDH were within normal limits. D-dimer was higher than the age-adjusted cutoff;CTA of the chest revealed no PE but showed bilateral ground glass opacities with consolidations. She tested positive for SARS-CoV-2. She was admitted for severe sepsis from COVID-19 pneumonitis and started on dexamethasone and remdesivir. SARS-CoV-2 IgG antibodies were positive. Given her immunocompromised status, bronchoscopy with BAL was performed and revealed copious thick secretions. Gram stain and bronchial brushings were negative for bacterial etiologies. Lavage culture was positive for aspergillus antigen and cytology revealed markedly enlarged reactive cells. Galactomannan serum antigen was positive. She was discharged on day 9 with a prolonged course of voriconazole. She had residual dyspnea on exertion but did not require supplemental O2. A nasal swab to test for variant strains was still pending. DISCUSSION: The COVID vaccine proved effective in preventing severe COVID-19 infections but trials excluded immunocompromised patients. This case of infection despite vaccination and detectable IgG titers reveals suboptimal protection. From data on pre-existing vaccines in immunocompromised patients, MTX is known to reduce immunogenicity. Our patient remained on immunosuppressants after vaccination, which may have contributed to her subsequent viral and fungal infections. Rheumatology guidelines suggest holding MTX for one to two weeks after vaccination to improve vaccine response. Employing this strategy will maximize immunogenicity against SARS-CoV-2 in immunocompromised patients. CONCLUSIONS: The American College of Rheumatology recommends vaccinating patients with rheumatological conditions against SARS-CoV-2. This case highlights individual patient factors to consider in the battle against COVID-19 in immunosuppressed patients. Non-viral infections must also be considered despite the ongoing pandemic. Determining protective antibody titers can guide booster vaccine recommendations. REFERENCE #1: Sonani B, Aslam F, Goyal A, Patel J, Bansal P. COVID-19 vaccination in immunocompromised patients. Clin Rheumatol. 2021;40(2):797-798. doi:10.1007/s10067-020-05547-w REFERENCE #2: Day AL, Winthrop KL, Curtis JR. The effect of disease-modifying antirheumatic drugs on vaccine immunogenicity in adults. Cleve Clin J Med. 2020;87(11):695-703. Published 2020 Nov 2. doi:10.3949/ccjm.87a.20056 REFERENCE #3: COVID-19 Vaccine Clinical Guidance Summaryfor Patients with Rheumatic and Musculoskeletal Diseases DISCLOSURES: No relevant relationships by Vernon Chan, source=Web Response No relevant relationships by Dana Daoud, source=Web Response No relevant relationships by Jeet Lund, source=Web Response

The effect of disease-modifying antirheumatic drugs on vaccine immunogenicity in adults.

Patients with immunocompromising conditions are at higher risk of vaccine-preventable infections. Further, those receiving immunosuppressive disease-modifying antirheumatic drugs (DMARDs) can have variable responses to vaccines depending on which vaccine and which DMARD they are receiving.

Prevalence of coronavirus disease 2019 in rheumatic patients and evaluation of the effect of disease-modifying anti-rheumatic drugs.

One of the most controversial issues among rheumatologists is the best approach to managing a rheumatic patient (RP) with coronavirus disease 2019 (COVID-19). This study aims to evaluate the prevalence of COVID-19 in RPs compared to the general population and to relatively assess the potential role of RPs’ treatment regimen against COVID-19. In a cross-sectional study, all RPs with an updated medical record between December 1, 2019, and February 29, 2020, at the rheumatology clinic of Shahid Beheshti Hospital, Qom, Iran were included (as the case group), and the prevalence of COVID-19 was compared to the paired control group—individuals without RDs, randomly selected from the Qom Health Network’s database. Qom was the first city in Iran in which COVID-19 was identified and spread rapidly. Both groups were paired regarding sex, age, and underlying severe conditions. The prevalence of COVID-19 was lower in RPs than the control group (p = 0.028). Moreover, patients who were under treatment with disease-modifying anti-rheumatic drugs (DMARDs) and biologic agents seemed to possess a lower risk for COVID-19. Two RPs died from COVID-19, both of whom had granulomatosis and polyangiitis (GPA). The prevalence of COVID-19 in the RPs was lower than the control group, which could be associated with more adherence to the quarantine and social distancing rules by RPs and stricter routine follow-ups than the general population. Besides, taking DMARDs, such as leflunomide, might possess a protective effect against severe COVID-19, probably as a result of preventing cytokine storm.

Cognitive impairment in elderly patients with rheumatic disease and the effect of disease-modifying anti-rheumatic drugs.

Recent development of biologic disease-modifying anti-rheumatic drugs (DMARDs) has led to better control of disease activity among patients with chronic rheumatological diseases. Many patients with rheumatic disease are living longer, adding to the growing elderly population. Rheumatic diseases, most notably rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are known to increase the risk of cognitive impairment. Systemic inflammation associated with chronic rheumatological diseases has been postulated to be key driver of cognitive decline. Recent development of classic and biologic DMARDs have led to better control of disease activity among patients with rheumatic conditions. It is proposed that strict control of systemic inflammation will significantly lower the risk of cognitive impairment among patients with rheumatic disease. The impact of classic DMARDs on cognitive function appears to be variable. On the other hand, biologic DMARDs, specifically antitumor necrosis factor (TNF) drugs (i.e., etanercept), have been shown to significantly lower the risk of dementia. Experimental studies on IL-1, IL-6, and B and T cell blockade are promising. However, clinical data is limited. Preclinical studies on targeted therapies, specifically JAK/STAT inhibitors, also show promising results. Additional studies are necessary to better understand the impact of these newer biologic agents on cognitive function in elderly patients with rheumatic disease. Key points • Patients with chronic rheumatic conditions are beginning to live longer, adding to the elderly population. • Patients with chronic rheumatologic disease are at increased risk of cognitive impairment compared to the general population. • Recent development of biologic (i.e., TNF, IL-1, IL-6) and targeted drugs (i.e., Janus kinase inhibitors) have led to better control of disease activity. • Current evidence suggests that TNF inhibitors may have beneficial effects on cognitive function. However, evidence on newer biologic and targeted therapies is limited.

Non-anti-TNF biologic agents are associated with slower worsening of interstitial lung disease secondary to rheumatoid arthritis.

To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD). We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24months. The radiological assessment was centralized. The main outcome measure at 24months was changed in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD. After 24months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%). Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non-anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening. Key Points • We have performed prospectively evaluated lung and joint function in patients with RA-ILD receiving treatment with various DMARDs. • In our study, the lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. • Neither csDMARDs nor anti-TNF agents were associated with a significant risk of worsening of lung disease, whereas non-anti-TNF bDMARDs could reduce the risk of worsening of lung disease. • Smoking and poor control of joint involvement were the main factors associated with worsening of lung disease.

OP0037 NON–ANTI-TNF BIOLOGIC AGENTS ARE ASSOCIATED WITH LESS MARKED PROGRESSION OF INTERSTITIAL LUNG DISEASE SECONDARY TO RHEUMATOID ARTHRITIS

Background:Objectives:To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (ILD-RA).Methods:We performed a multicenter, prospective, observational study of patients with ILD-RA receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and lung function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was change in lung function (improvement, non-progression, progression, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with progression of ILD.Results:We included 70 patients with ILD-RA treated with DMARDs. The main baseline characteristics are shown in Table 1. After 24 months, lung disease did not progress in 40 patients (57.1%), improved in 8 (11.4%), and progressed in 21 (30.0%). One patient (1.4%) died. The factors associated with progression of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%).Conclusion:Lung function is stable and inflammatory activity well controlled in most patients with ILD-RA receiving treatment with DMARDs. Non–anti-TNF DMARDs reduce the risk of progression of lung disease in 90% of patients, whereas the inflammatory activity of RA and smoking are associated with progression.Table:VariablePatients=70Epidemiological characteristicsFemale sex, n (%)39 (55.7)Age, y, mean (SD)68.8 (7.8)Clinical-laboratory characteristicsSmoking historyNever smoked, n (%)23 (32.9)Smoked, n (%)47 (67.1)Time since diagnosis of RA,(months),mean (SD)161.0 (125.9)Diagnostic delay,(months),median (IQR)12.0 (5.9-24.0)Time since diagnosis of ILD,(months),mean (SD)42.3 (48.3)Positive rheumatoid factor (>10), n (%)65 (92.0)Anticitrullinated protein antibody (>20), n (%)58 (82.9)Synthetic DMARDs64 (91.4)Methotrexate, n (%)30 (42.9)Leflunomide, n (%)16 (22.9)Sulfasalazine, n (%)8 (11.4)Hydroxychloroquine, n (%)10 (14.3)Biologic DMARDs27 (38.1)Infliximab, n (%)1 (1.4)Etanercept, n (%)4 (5.7)Adalimumab, n (%)1 (1.4)Golimumab, n (%)1 (1.4)Certolizumab, n (%)0 (0.0)Tocilizumab, n (%)5 (6.2)Abatacept, n (%)5 (6.2)Rituximab, n (%)10 (14.3)Other immunosuppressantsMycophenolate, n (%)4 (5.7)Azathioprine, n (%)1 (1.4)Disclosure of Interests:None declared

Effect of disease-modifying anti-rheumatic drugs on bone structure and strength in psoriatic arthritis patients

ObjectivesTo address whether the use of methotrexate (MTX) and biological disease-modifying anti-rheumatic drugs (bDMARDs) impacts bone structure and biomechanical properties in patients with psoriatic arthritis (PsA).MethodsThis is a cross-sectional study in PsA patients receiving no DMARDs, MTX, or bDMARDs. Volumetric bone mineral densities (vBMDs), microstructural parameters, and biomechanical properties (stiffness/failure load) were determined by high-resolution peripheral quantitative CT and micro-finite element analysis in the respective groups. Bone parameters were compared between PsA patients with no DMARDs and those receiving any DMARDs, MTX, or bDMARDs, respectively.ResultsOne hundred sixty-five PsA patients were analyzed, 79 received no DMARDs, 86 received DMARDs, of them 52 bDMARDs (TNF, IL-17- or IL-12/23 inhibitors) and 34 MTX. Groups were balanced for age, sex, comorbidities, functional index, and bone-active therapy, while disease duration was longest in the bDMARD group (7.8 ± 7.4 years), followed by the MTX group (4.6 ± 7.4) and the no-DMARD group (2.9 ± 5.2). No difference in bone parameters was found between the no-DMARD group and the MTX group. In contrast, the bDMARD group revealed significantly higher total (p = 0.001) and trabecular vBMD (p = 0.005) as well as failure load (p = 0.012) and stiffness (p = 0.012). In regression models, age and bDMARDs influenced total vBMD, while age, sex, and bDMARDs influenced failure load and stiffness.ConclusionDespite longer disease duration, bDMARD-treated PsA patients benefit from higher bone mass and better bone strength than PsA patients receiving MTX or no DMARDs. These data support the concept of better control of PsA-related bone disease by bDMARDs.

Opioid use in rheumatoid arthritis: trends, efficacy, safety, and best practices.

The opioid epidemic remains prominent in both the medical literature and popular media. Rheumatologists are among the physicians at the forefront of the epidemic because of the prominent role of pain in rheumatoid arthritis (RA) and the limited options for treatment of pain. The purpose of this review is to provide an update on the trends of opioid use among patients with RA, to discuss the various mechanisms of RA pain, review the available evidence for opioid efficacy in RA, and to promote a guideline for best practices in opioid prescribing. Recent cohort studies have estimated that up to 40% of patients with RA are regular users of opioids, and the effects of disease-modifying antirheumatic drugs are minimal in reducing opioid use. Although the literature supports the efficacy of short-term opioids for the improvement in pain, long-term use is associated with reduced efficacy and increased safety concerns. Although the data supporting the use of long-term opioid use in patients with RA is poor, rheumatologists can adhere to best practices for determining when and if initiation of opioids is appropriate. Identification of the nature of the pain can help determine the appropriate course of treatment.

Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases.

The cardiovascular effects of disease-modifying antirheumatic drugs and particularly of methotrexate (MTX) are complex and frequently incorrectly understood, which might lead to the unjustified discontinuation of this treatment. MTX, 'the gold standard' and first line treatment in rheumatoid arthritis, psoriatic arthritis, and other immune-mediated inflammatory diseases, has been proven to decrease inflammation, improve cardiovascular risk factors, and reduce mortality. This is supported by both the mechanism of action, as well as a body of clinical data evidence. MTX's cardiovascular effects, although incompletely understood, are explained by its antiproliferative, immunosuppressive, anti-inflammatory, and antiatherogenic effects. Several clinical trials have shown that MTX is associated with improved endothelial function, slower atherosclerosis progression, decreased risk of major cardiovascular adverse events, and benefits on survival. Given its systemic cardiovascular effects, MTX could be regarded as an important therapeutic agent not only to control disease activity in rheumatic diseases, but also to reduce cardiovascular risk and mortality.

Atherosclerosis in Rheumatoid Arthritis: Promoters and Opponents.

Substantial epidemiological data identified cardiovascular (CV) diseases as a main cause of mortality in patients with rheumatoid arthritis (RA). In light of this, RA patients may benefit from additional CV risk screening and more intensive prevention strategies. Nevertheless, current algorithms for CV risk stratification still remain tailored on general population and are burdened by a significant underestimation of CV risk in RA patients. Acute CV events in patients with RA are largely related to an accelerated atherosclerosis. As pathophysiological features of atherosclerosis overlap those occurring in the inflamed RA synovium, the understanding of those common pathways represents an urgent need and a leading challenge for CV prevention in patients with RA. Genetic background, metabolic status, gut microbiome, and systemic inflammation have been also suggested as additional key pro-atherosclerotic factors. The aim of this narrative review is to update the current knowledge about pathophysiology of atherogenesis in RA patients and potential anti-atherosclerotic effects of disease-modifying anti-rheumatic drugs.

Effect of disease-modifying anti-rheumatic drugs on therapeutic outcomes among women with endometriosis.

To determine whether disease-modifying anti-rheumatic drugs (DMARDs) affect the use of hormonal treatments, subsequent ablative surgery, and need for pain management, including opioids, non-steroidal anti-inflammatory drugs and anti-depressants, among women with endometriosis. In a retrospective study, data were reviewed from women with surgically confirmed endometriosis who were not treated (n=234) or treated with DMARDs for 6weeks or more (n=25) before surgical diagnosis at a single healthcare system in the USA between 2003 and 2013. The postoperative use of hormonal treatments, proportion of women undergoing subsequent ablative surgery, and use of adjunct therapies such as antidepressants, steroids, and opioids after surgery were compared between the two groups. The two groups showed differences in age (P=0.007) and follow-up time (P<0.001). Univariate analysis showed more frequent use of hormonal treatments (P=0.045) and antidepressants (P=0.006) among women treated with DMARDs. The frequency of post-diagnostic use of opioids was lower among treated women (P=0.001); this association remained significant in multivariate analysis controlling for potential confounders (P=0.003). The findings suggest that administration of DMARDs for at least 6weeks is associated with decreased opioid usage among women with endometriosis.

EFFECTS OF SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS, BIOLOGICAL AGENTS, AND PSYCHOPHARMACOTHERAPY ON THE MENTAL DISORDERS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Mental disorders (MDs) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) are characteristic of the majority of patients with rheumatoid arthritis (RA); however, the effects of disease-modifying antirheumatic drugs (DMARDs), biological agents (BAs), and their combinations with psychopharmacological drugs (PPDs) on these abnormalities have been insufficiently studied. Objective: to investigate trends in the incidence of MDs in RA patients receiving different treatment regimens.Subjects and methods. The investigation included 128 RA patients (13% men and 87% women) who fulfilled the 1987 American College of Rheumatology criteria; their mean age was 47.4±0.9 years; the median duration of RA was 96 [48; 228] months. RA activity was found to be high, moderate, and low in 48, 56, and 24 patients, respectively. DAS28 averaged 5.34±0.17. 80% of the patients received DMARDs. MDs were diagnosed based on ICD-10 coding, by using a semi-structured interview and scales, such as the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale, and the Montgomery-Asberg Depression Rating Scale. Clinical and psychological procedures were used to diagnose CI. At the study inclusion stage, ADS disorders were detected in 123 (96.1%) patients; CI was found in 88 (68.7%). Forty-one (32.1%) patients were diagnosed with major depression (an obvious or moderate depressive episode), 53 (41.4%) patients had minor depression (a mild depressive episode and dysthymia), and 29 (22.6%) had anxiety disorders (ADs) (adjustment disorders with anxiety symptoms, as well as generalized anxiety disorder). The dynamics of MDs was estimated in 112 (87.5%) of the 128 patients and in 83 (64.8%) at one- and five-year follow-ups, respectively. The following groups were identified according to the performed therapy: 1) synthetic DMARDs (n = 39); 2) synthetic DMARDs + PPDs (n = 43); 3) BAs + DMARDs (n = 32); 4) BAs + DMARDs + PPDs (n = 9).Results and discussion. In Group 1, the frequency of major depression increased insignificantly from 25% to 32.2 and 33.3% (p = 0.36) at one- and five-year follow-ups, respectively; that of minor depression decreased from 51% to 48.4 (p = 0.5) and 50% (p = 0.6) respectively; the number of patients with ADs declined significantly from 24% to 3.2 (p = 0.018) and 4.2% (p = 0.021), respectively. The frequency of CI rose from 63.5% to 64.5 and 81.8%, respectively (p = 0.12). In Group 2, the frequency of major depression decreased from 43 to 19% (p = 0.049) at one-year follow-up; and none of the patients was found to have ADS disorders at five-year follow-up (p &lt; 0.001); the frequency of minor depression dropped from 38% to 23.8 and 7.1% at one-year (p = 0.35) and five-year (p = 0.002) follow-ups, respectively; the frequency of ADs fell from 19% to 4.8 (p = 0.044) and 0% (p = 0.012), respectively. The frequency of CI decreased insignificantly from 80.9% to 76.2 (p = 0.39) and 61.5% (p = 0.061), respectively. In Group 3 treated with BAs, the frequency of major depression increased statistically insignificantly from 31.2% to 37.9 (p = 0.39) and 42.8% (p = 0.28) at oneand five-year follow-ups, respectively; the frequency of minor depression rose insignificantly from 37.5% to 48.3 (p = 0.28) and 52.4% (p = 0.21), respectively; and that of ADs dropped from 25 to 0% at one-year (p = 0.003) and five-year (p = 0.011) follow-ups. Moreover, the frequency of CI increased from 75% up to 79.3 (p = 0.46) and 90% (p = 0.16) at one- and five-year follow-ups respectively. In Group 4, the frequency of major depression decreased significantly from 66.7 to 22.2% (p = 0.076) and complete regression (p = 0.004) at one- and five-year follow-ups, respectively; that of minor depression increased slightly from 11.1 to 33.3% (p = 0.28) due to the transformation of major depression into minor one at one- and five-year follow-ups, respectively; the frequency of ADs fell from 22.2% to zero at 5 years; and the incidence of CI declined 66.7 to 57.1% (p = 0.54).Conclusion. Synthetic DMARDs had no effect on the ADS disorders and CI in patients with RA; BAs promoted the regression of ADs and did not affect the progression of depression and CI. A combination of DMARDs and BAs used at the adequate dose of PPDs for the same period led to the regression of ADS disorders and the reduction in the frequency of CI.