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33609791 Risk factors for hypertension in rheumatoid arthritis patients-A systematic review. 2021 Apr INTRODUCTION: Rheumatoid arthritis is frequently associated with hypertension, which has been shown to increase the risk of cardiovascular disease in these patients. The aim of this systematic review was to explore demographic, behavioural or clinical factors including medication use, associated with incident hypertension in rheumatoid arthritis. METHODS: MEDLINE and Scopus were searched for eligible studies that longitudinally investigated incident hypertension or changes in blood pressure (BP) in rheumatoid arthritis patients. Publications were screened by two reviewers according to predetermined inclusion and exclusion criteria. The quality of included studies was assessed via the Newcastle Ottawa Scale and Cochrane Risk of Bias Tool. RESULTS: Fourteen studies were deemed eligible and included in this review. The proportion of female subjects ranged from 12 to 87% and the mean age ranged from 47 to 61 years. Regular exercise was associated with a decrease in systolic BP, p = 0.021. Methotrexate was associated with decreased risk of hypertension in two studies. LEF was associated with increased BP in two studies. COX-2 inhibitors were associated with systolic BP and diastolic BP variability (p = 0.009, 0.039, respectively) in one study. Prednisone was found to increase BP and risk of hypertension in three studies. The risk of hypertension in patients taking biologic disease modifying anti-rheumatic drugs (DMARDs) is unclear as some studies report increased BP while others report no difference for biologic compared to conventional DMARDs. CONCLUSION: Despite limited longitudinal studies exploring this topic, methotrexate and exercise were shown to protect against risk of hypertension in RA patients, while prednisone and COX-2 inhibitors may increase risk of hypertension.
33509333 Pulmonary Manifestations of Rheumatoid Arthritis. 2021 Feb 1 OBJECTIVE: To describe the case of an 88-yearold male with rheumatoid arthritis who developed pulmonary manifestations. Treatment for his RA previously included various biologics, while at the time of pulmonary consultation included meloxicam, methotrexate, and abatacept. Following chest scans, bronchoscopy, needle biopsy, pulmonary function testing, and a thoracentesis, the diagnosis of pleural effusion and nodules associated with rheumatoid arthritis was determined. The patient was recommended to follow-up with the pulmonologist but was lost to follow-up because of nonpulmonary and nonrheumatoid arthritis complications.
SETTINGS: Ambulatory clinic pharmacy practice, Community pharmacy, Consultant pharmacy practice.
PRACTICE CONSIDERATIONS: Drugs used to treat rheumatoid arthritis may produce pulmonary toxicity similar to what is seen with the disease itself. Drug therapy may require modification if identified as an offending agent causing pulmonary manifestations. If fibrosing interstitial lung disease develops, the addition of nintedanib may need to be considered.
CONCLUSION: In order for pharmacists to better assist providers and patients and improve therapeutic outcomes, it is important for pharmacists to understand that pulmonary manifestations are common in patients having rheumatoid arthritis as well as with drugs used to treat rheumatoid arthritis.
34975886 Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor 2021 Rheumatoid arthritis (RA) is a disabling autoimmune disease with invasive arthritis as the main manifestation and synovitis as the basic pathological change, which can cause progressive destruction of articular cartilage and bone, ultimately leading to joint deformity and loss of function. Since its introduction in the 1980s and its widespread use in the treatment of RA, low-dose methotrexate (MTX) therapy has dramatically changed the course and outcome of RA treatment. The clinical use of this drug will be more rational with a better understanding of the pharmacology, anti-inflammatory mechanisms of action and adverse reaction about it. At present, the current clinical status of newly diagnosed RA is that MTX is initiated first regardless of the patients' suitability. But up to 50% of patients could not reach adequate clinical efficacy or have severe adverse events. Prior to drug initiation, a prognostic tool for treatment response is lacking, which is thought to be the most important cause of the situation. A growing body of studies have shown that differences in microbial metagenomes (including bacterial strains, genes, enzymes, proteins and/or metabolites) in the gastrointestinal tract of RA patients may at least partially determine their bioavailability and/or subsequent response to MTX. Based on this, some researchers established a random forest model to predict whether different RA patients (with different gut microbiome) would respond to MTX. Of course, MTX, in turn, alters the gut microbiome in a dose-dependent manner. The interaction between drugs and microorganisms is called pharmacomicrobiology. Then, the concept of precision medicine has been raised. In this view, we summarize the characteristics and anti-inflammatory mechanisms of MTX and highlight the interaction between gut microbiome and MTX aiming to find the optimal treatment for patients according to individual differences and discuss the application and prospect of precision medicine.
33689031 [Glucocorticoid-free and low-dose glucocorticoid treatment of rheumatoid arthritis]. 2021 May Systemic glucocorticoids (GC) are a commonly used component in the treatment of rheumatoid arthritis. The aim of this article is to show the evidence for low-dose GC or GC-free RA treatment regimens. Furthermore, concepts for the de-escalation of GC treatment for RA are presented. There is sufficient evidence in the initial phase that GC treatment in addition to methotrexate (MTX) improves the patient's response to the disease activity as well as the subjective perception of impairments. The dosage of GC, however, needs to be weighed critically and the guideline-based gradual reduction leading eventually to discontinuation must consistently be pursued. In the later phases of the treatment algorithm the risks of GC administration outweigh the benefits and long-term GC treatment should therefore be reserved for exceptional cases. The lowest possible dosage always needs to be determined individually. This can be achieved by using a clinically tested scheme of reducing the prednisolone intake by 1 mg every 4 weeks. The scheme should be considered for patients with a low disease activity or remission due to disease-modifying antirheumatic drug (DMARD) treatment, if they receive 5 mg of prednisolone as long-term treatment. On the whole the positive subjective effects of GC treatment must always be weighed up against the risks of such treatment for RA patients. An ongoing process of readjusting treatment following shared-decision rules must both consistently adapt GC doses and constantly check the indications. Even if a GC-free treatment does not seem realistic, a low-dose GC treatment of RA still is and should be pursued to reduce the risks associated with the treatment.
33597206 Risk for infections with glucocorticoids and DMARDs in patients with rheumatoid arthritis. 2021 Feb Immunomodulatory therapy for rheumatoid arthritis (RA) carries risk for infectious complications. Understanding the risks of different therapeutic options is essential for making treatment decisions and appropriately monitoring patients. This review examines data on the risks for serious infections and other key infections of interest for the major classes of agents in use for RA: glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologics and Janus kinase (JAK) inhibitors. Conventional synthetic DMARDs have an excellent safety profile with recent data available supporting the relative safety of methotrexate. Tumour necrosis factor (TNF) inhibitors are associated with an increase in the risk of serious infections. Risk with other biological agents and with JAK inhibitors varies somewhat but overall appears similar to that of TNF inhibitors, with JAK inhibitors also associated with a greater risk of herpes zoster. Glucocorticoids have a dose-dependent effect on serious infection risk-at higher doses risk of infection with glucocorticoids is substantially greater than with other immunomodulatory therapies, and even low-dose therapy carries a risk of infection that appears to be similar to that of biological therapies.
33638167 Variability of rituximab and tocilizumab trough concentrations in patients with rheumatoid 2021 Dec Patients with rheumatoid arthritis (RA) are eligible for treatment with therapeutic monoclonal antibodies (mAbs) that target tumor necrosis factor α (TNFα), as well as others, such as rituximab (RTX) and tocilizumab (TCZ). Although pharmacokinetic variability and the link between concentration-clinical response of anti-TNFα mAbs have been well-described, little is known about RTX and TCZ. We aimed to evaluate the variability of RTX and TCZ serum concentrations in RA patients treated in second-line and the relationship between RTX/TCZ concentrations and the clinical response. Serum mAb trough concentrations of RA patients treated with RTX (n = 35) or TCZ (n = 46) were determined at week 24 by liquid chromatography-tandem mass spectrometry. The clinical response was assessed at week 24 by the change in the disease activity score in the 28 joints-erythrocyte sedimentation rate from baseline (ΔDAS28-Erythrocyte Sedimentation Rate) and according to the European League Against Rheumatism (EULAR) recommendations. RTX and TCZ trough concentrations were highly variable, with a coefficient of variation of 171.3% for RTX (median [10th-90th percentiles]: <1.0 µg/mL [<1.0-5.1]) and 132.6% for TCZ (median [10th-90th percentiles]: 5.4 µg/mL [<1.0-27.8]). Univariate analysis did not identify any determinants of such variability, except cotreatment with methotrexate, which was associated with lower RTX concentrations (P = 0.03). The response to treatment was not related to the RTX or TCZ trough concentration. RTX and TCZ trough concentrations at 24 weeks were highly variable in RA patients treated in the second line, without any link concentration-clinical response having been demonstrated.
34016483 Triggers of Cardiovascular Diseases in Rheumatoid Arthritis. 2022 Jun The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is higher than that in patients without RA, and it is even higher than that in patients with diabetes. Autoimmune-mediated inflammation is observed in patients with RA, resulting in endothelial dysfunction, oxidative stress and activation, and vascular migration of white blood cells. Traditionally, RA-associated CVD was assumed to be mediated by disease-related inflammation, resulting in atherosclerosis (AS). However, this concept has been challenged because treatment with anti-rheumatic drugs, such as methotrexate or proinflammatory cytokine antagonists, such as tumor necrosis factor-alpha (TNF-α) inhibitors, did not reduce the risk of CVD in patients with RA. Current cardiovascular guidelines recommend screening and treatment of CVD risk factors in patients with RA but without clear biomarkers and treatment goals. There is no scientific basis for establishing therapeutic targets for cardiovascular risk factors in RA. Numerous studies have shown that the mechanism of early cardiac dysfunction in patients with RA may occur prior to AS. Therefore, it is crucial to explore the related mechanisms to prevent early cardiac dysfunction in patients with RA.
34536550 A review of liquid biopsy as a tool to assess epigenetic, cfDNA and miRNA variability as m 2021 Nov Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease affecting 0.5-1% of adults worldwide. Achieving long term remission or low disease activity is possible through early diagnosis, rapid initiation of disease modifying anti-rheumatic drugs (DMARDs) and implementation of a treat to target approach. Initial DMARD therapy usually involves methotrexate (MTX), either alone or in combination with other agents, however 40% of RA patients do not respond adequately, putting them at risk of disease progression and unnecessary exposure to MTX related adverse effects. Early predictors of MTX response would therefore enable a more personalized treatment strategy, ensuring timely access to MTX for those likely to respond and importantly, early initiation of alternative treatment for those in which MTX is unlikely to be efficacious. Predicting response to treatment will most likely require consideration of the clinical characteristics of the patient and interrogation of a number of factors including genetic, epigenetic, cell free DNA (cfDNA) and microRNA (miRNA), all of which can be investigated through blood derived liquid biopsies. This review will summarize the existing literature examining the use of epigenetic factors, cfDNA and miRNA as response predictors among RA patients treated with MTX.
33210179 Efficacy of methotrexate in reducing the risk of bone erosion in patients with rheumatoid 2021 May Even though new drugs for the treatment of rheumatoid arthritis (RA) have been developed, methotrexate (MTX) remains a commonly used drug for RA management. In addition to monitoring disease activity during RA treatment, bone erosion should be closely assessed throughout long-term RA management. In this review article, we present a systematic review of MTX effectiveness in reducing the risk of bone erosion. We reviewed randomized controlled trial studies that involved MTX monotherapy or MTX in combination with placebo. Evaluation of the progression of bone erosion was examined by radiographic assessment such as total Sharp score (TSS) or van der Heijde score (SvdH or vdH TSS), joint space narrowing (JSN), erosion score (ERO), and proportion of radiographic nonprogressors. Several key factors were found to influence the response to MTX treatment, such as gene polymorphism. The exact mechanism of the prevention of bone erosion by MTX remains unclear, which warrants future investigations. The variability of RA disease activity in study subjects resulted in variations in the results reported by individual studies. Collective analysis suggests that MTX could slow down the progression of bone erosion based on a radiographic score of less than 0.5-1/year.
35096346 Immunologic Parameters for Disease Activity in Rheumatoid Arthritis. 2021 Oct This study aimed to determine the correlation of disease activity of rheumatoid arthritis (RA) with Th17/regulatory T cell (Treg) and Forkhead box protein 3 (Foxp3) cells ratio in patients under therapy with anti-tumor necrosis factor (TNF)-α. Totally, 84 patients with RA and 13 healthy controls were included in this case-control study. The patients were divided into four groups to receive only methotrexate (MTX) (n=25), monotherapy (anti-TNF) (n=18), and combined therapy (MTX+anti-TNF) (n=26); however, one group received no medications (n=15) and was regarded as a positive control. Other 13 healthy controls that were considered negative controls were also enrolled in this study. Patients with RA were attending Basrah General Hospital, Rheumatology Unit, Biological Therapy Center for receiving anti-TNF therapy. Flow cytometry was used for measuring Treg/Foxp3 and Th17 markers, and the DAS-28 score was utilized to measure RA disease activity. Anti-TNF inhibitors (e.g., infliximab and etanercept), as well as other inflammatory and hematological parameters (e.g., erythrocyte sedimentation rate, total white blood cells, lymphocytes, monocytes, and neutrophil counts), were also measured in this study. DAS-28 as a disease activity score was significantly correlated with Th17/Treg/Foxp3 ratio and the Th17 cells count. Statistically, Th17/Treg/Foxp3 ratio was not correlated with body mass index, morning stiffness, and duration of the disease. Th17/Treg/Foxp3 ratio correlated significantly with DAS-28 as an RA disease activity. The lower Treg/Foxp3 frequency led to the higher DAS score reflecting higher disease activity. In the combined therapy group, disease activity was found lower than that in other patient groups indicating the effect of this combination on the relationship between MTX and anti-TNF. This study demonstrated that the main advantage of this combined therapy in RA patients was the reversion of Th17 cell expansion.
34537063 Risk of rheumatoid arthritis diagnosis in statin users in a large nationwide US study. 2021 Sep 18 OBJECTIVE: To evaluate the association between statin use and the risk of developing rheumatoid arthritis (RA) in a large, US case-control study. METHODS: Using the OptumLabs Data Warehouse, RA cases were identified as patients aged ≥18 years with ≥2 RA diagnoses between January 1, 2010 and June 30, 2019 and ≥1 prescription fills for methotrexate within 1 year of the first RA diagnosis. The first RA diagnosis was the index date. Cases were matched 1:1 to controls on age, sex, region, year of index date, and length of baseline coverage. Statin users were defined by having ≥2 statin prescription fills at least 90 days pre-index. Patients identified as statin users were further classified by statin user status (current or former), statin use duration, and intensity of statin exposure. Odds ratios for RA risk with statin use were estimated using logistic regression. RESULTS: 16,363 RA cases and 16,363 matched controls were identified. Among RA cases, 5509 (33.7%) patients were statin users compared to 5164 (31.6%) of the controls. Statin users had a slightly increased risk of RA compared to non-users (OR 1.12, 95% CI 1.06-1.18), and former statin users had an increased RA risk compared to current users (OR 1.21, 95% CI 1.13-1.28). However, risk was eliminated following adjustment for hyperlipidemia. The risk estimates for statin use duration and intensity did not reach significance. CONCLUSION: This study demonstrates no significant increase in the risk of developing RA for statin users compared to non-users after adjustment for hyperlipidemia in addition to other relevant confounders. However, more information from prospective studies would be necessary to further understand this relationship.
34370914 Prevalence of periapical abscesses in patients with rheumatoid arthritis. A cross sectiona 2021 Aug PURPOSE: To assess the prevalence of periapical abscesses in patients with rheumatoid arthritis, and to evaluate the effect of commonly used antirheumatic medications on such prevalence. METHODS: Integrated data of hospital patients was used. Data from the corresponding diagnosis codes for rheumatoid arthritis and periapical abscess was retrieved by searching the appropriate query in the database. The odd ratio (OR) of periapical abscesses, its association with rheumatoid arthritis and intake of three commonly prescribed antirheumatic medications were calculated and analyzed statistically. RESULTS: The prevalence of periapical abscesses in patients with rheumatoid arthritis was 1.53% as compared to 0.51% in the general patient population of the hospital. The OR was 2.60 and the difference was statistically significant (P< 0.0001). In patients treated with either Methotrexate, Sulfasalazine, or Etanercept, the ORs were 2.88, 3.1, and 1.07, respectively. The differences between Methotrexate and Sulfasalazine were statistically significant (P< 0.0001). The OR for prevalence of periapical abscesses in patients treated with Etanercept was significantly lower than that of patients treated with either Methotrexate or Sulfasalazine (P< 0.005). CLINICAL SIGNIFICANCE: Oral healthcare providers should be aware of the possible association between rheumatoid arthritis and occurrence of periapical abscesses. Patients with rheumatoid arthritis, mainly women, may exhibit higher prevalence of periapical abscesses. Treatment with TNF alpha inhibitors may lower the prevalence of periapical abscesses in such patients.
33843457 Abatacept for rheumatoid arthritis complicated by disseminated cryptococcosis: a case repo 2021 Jul A 78-year-old man developed disseminated cryptococcosis with central nervous system involvement as encapsulated yeast cells were detected in transbronchial biopsy and skin biopsy specimens, and cerebrospinal fluid. Cryptococcus neoformans was confirmed by culture. He had been treated with low-dose prednisolone and methotrexate for rheumatoid arthritis. He started receiving antifungal therapy with intravenous liposomal amphotericin B followed by oral fluconazole. Methotrexate was discontinued. Approximately 4 months after the course of intravenous liposomal amphotericin B was completed, he complained of pain and swelling of the right wrist, which suggested that rheumatoid arthritis was worsening. Abatacept therapy was initiated along with antifungal therapy, and his symptoms relieved. After 24 months of antifungal therapy, although he was still receiving oral fluconazole, he was doing well and the serum cryptococcal antigen had become negative. Disseminated cryptococcosis is an important opportunistic infection associated with low-dose methotrexate for rheumatoid arthritis. Abatacept therapy may be feasible in strictly selected patients with rheumatoid arthritis complicated with cryptococcosis concomitantly with intensive anti-fungal therapy.
34446133 Lipidated Methotrexate Microbubbles: A Promising Rheumatoid Arthritis Theranostic Medicine 2021 Jul 1 De novo designed lipidated methotrexate was synthesized and self-assembled into microbubbles for targeted rheumatoid arthritis theranostic treatment. Controlled lipidatedmethotrexate delivery was achieved by ultrasound-targetedmicrobubble destruction technique. Methotrexate was dissociated inflammatory microenvironment of synovial cavity, owing to representive low pH and enriched leucocyte esterase. We first manipulated methotrexate controlled release with RAW 264.7 cell line in vitro and further verified with rheumatoid arthritis rabbits in vivo. Results showed that lipidated methotrexate microbubbles precisely affected infection focus and significantly enhanced rheumatoid arthritis curative effect comparing with dissociative methotrexate. This study indicates that lipidated methotrexate microbubbles might be considered as a promising rheumatoid arthritis theranostics medicine.
33081597 A case of rheumatoid arthritis complicated with mucous membrane pemphigoid. 2021 Jul Rheumatoid arthritis (RA) is a disease of unknown aetiology that causes irreversible joint destruction and has been known to present with not only various extra-articular symptoms, but also various autoimmune disorders. Mucous membrane pemphigoid (MMP) is a chronic autoimmune disease characterised by inflamed and eroded mucosa. The prognosis of MMP can be poor, so early diagnosis and prompt initiation of therapy are necessary for optimal management. Here, we report a rare case of RA complicated with MMP involving a 68-year-old woman admitted to our hospital because of hoarseness and symmetrical narrowing of the eye fissures. She presented with bilateral coxalgia and had been diagnosed with RA 24 years earlier. Oral methotrexate was prescribed, but subsequently discontinued, and this was followed by treatment with tocilizumab 3 years earlier. Tocilizumab was discontinued because of financial distress 5 months earlier, after which her RA disease activity worsened. She presented to our hospital after further worsening of her eye-opening difficulty. Physical and laboratory examinations led to a diagnosis of MMP. Her sputum, cough, throat discomfort, conjunctival congestion, mucous erosion, and blistering promptly disappeared after treatment with rituximab (500 mg per week for 4 weeks). She subsequently recovered her vocalisation ability, and her hoarseness, dysphagia, and eye-opening difficulty gradually improved, but not completely. This case suggests that that RA and MMP share common immunological mechanisms. Therefore, MMP should be considered when encountering patients with RA who present with systemic membrane mucous disorders.
34559494 Frequency of positivity of the tuberculin intradermorreaction test in a cohort of patients 2021 Sep 22 Introduction: Rheumatoid arthritis is an autoimmune, chronic, and deforming condition associated with disability. Patients are immunosuppressed and at high risk of developing tuberculosis. The tuberculin skin test is used to screen candidates for biological therapy. Objective: To evaluate the frequency of positivity of the tuberculin skin test in a cohort of Colombian patients with rheumatoid arthritis. Materials and methods: We conducted a descriptive cross-sectional study including patients with rheumatoid arthritis receiving the tuberculin skin test prior to the start or at the time of the change of biological therapy. The patients’ condition was moderate or severe and they were candidates for initiation or change of biological therapy. We defined the value of ≥6 mm as the cut-off point for a positive tuberculin skin test and performed a descriptive analysis for each of the variables considered. Results: In total, 261 patients with rheumatoid arthritis were included, 92 % of whom were women; the average age was 55 years (SD=13.92) and the time from diagnosis, 12.3 years (SD=8.54). The frequency of positive tuberculin skin tests was 15.71% (n=41). Of the 41 positive patients, nine had previously had the test (1 to 6 years before), all of them with negative results; 18 of these were receiving glucocorticoids (43.9%) and all of them (100%) were being treated with methotrexate. Conclusions: The frequency of positivity of the tuberculin skin test in these Colombian patients diagnosed with rheumatoid arthritis was around 16%. We reco0mmend optimizing strategies aimed at an optimal detection of this condition and the timely initiation of treatment to reduce the risk of tuberculosis reactivation.
35096326 Effects of Naringenin on Experimentally Induced Rheumatoid Arthritis in Wistar Rats. 2021 Oct Naringenin is one of the most important and abundant known flavonoids found in grapefruit and other citrus fruits. This experimental study aimed to assess the clinical effects and immune responses of naringenin in the animal model of rheumatoid arthritis (RA) according to various reports on its anti-inflammatory effects and modulation of the immune system. To this end, 40 Wistar rats in the weight range of 160-180g were randomly assigned to four groups (n=10) including healthy, control, naringenin, and methotrexate orally treated groups. To induce RA disease, a compound of 200 μl of Freund's adjuvant and collagen type II was injected subcutaneously into the rear footpads of rats. The severity of RA clinical signs was assessed based on a standard scoring method. The treatment lasted for three weeks (days7-28 after induction). The obtained data pointed out that the levels of C-reactive protein (CRP), myeloperoxidase, nitric oxide, IL-17, and IFN-γ cytokines significantly increased in the RA rats, while the level of their serum antioxidants significantly reduced, compared to the healthy rats. The inflammation of the paws and the level of CRP decreased similarly in both methotrexate and naringenin-treated groups. In the naringenin-treated group, a further decrease was detected in serum myeloperoxidase, nitric oxide, and the total antioxidant capacity occurred, as compared to the methotrexate-treated rats. Nonetheless, IL-17 and IFN-γ cytokines levels were further decreased in the methotrexate-treated group. Accordingly, it can be concluded that naringenin can be effectively used for the reduction of inflammatory effects and control of RA disease.
31876844 Role of Interleukin 6 Inhibitors in the Management of Rheumatoid Arthritis. 2021 Dec 1 Rheumatoid arthritis (RA) is a multisystem disease that affects the joints and various organs, resulting in compromised quality of life and increased mortality. A wide spectrum of treatment options is available for RA. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are the first-line of treatment for RA, whereas tumor necrosis factor α inhibitors are commonly used as a second-line biological disease-modifying antirheumatic drug following inadequate response to csDMARDs. However, remission remains difficult to achieve. No single agent is effective for all patients. It is important to consider patients' comorbidities, perspectives, and preferences when selecting treatment.Interleukin 6 (IL-6) plays a prominent role in the pathophysiology of RA and is an important therapeutic target for RA. Tocilizumab and sarilumab are approved IL-6 inhibitors, which have demonstrated good efficacy and tolerability as combination therapy or monotherapy in RA patients with inadequate response to csDMARDs or tumor necrosis factor α inhibitors. Apart from alleviating joint symptoms, inducing remission, and reducing structural damage, tocilizumab and sarilumab exhibit additional advantages in alleviating extra-articular symptoms, such as fatigue and morning stiffness, and have positive effect on anemia and glucose metabolism. Additionally, evidence showed that certain patient subgroups, such as those with comorbidities including anemia and diabetes mellitus, those with early RA, those with high baseline IL-6 levels, those at high risk of tuberculosis infection, or those intolerant to methotrexate monotherapy, may benefit from IL-6 inhibition. Given these advantages, tocilizumab and sarilumab can be considered earlier as a rational choice for treating RA in suitable patients. Future clinical investigations will help refine the use of these agents.
33795331 Tuberculosis in Biologic-naïve Patients With Rheumatoid Arthritis: Risk Factors and Tuber 2021 Aug OBJECTIVE: To investigate risk factors and characteristics of active tuberculosis (TB) in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: We conducted a population-based case-control study using the Swedish Rheumatology Quality Register, the National Patient Register, and the Tuberculosis Register to identify RA patients with active TB and matched RA controls without TB between 2001-2014. Clinical data were obtained from medical records. TB risk was estimated as adjusted OR (aOR) with 95% CI using univariate and multivariable logistic regression analyses. RESULTS: After validation of diagnoses, the study included 31 RA patients with TB and 122 matched RA controls. All except 3 cases had reactivation of latent TB. Pulmonary TB was most prevalent (84%). Ever use of methotrexate was not associated with increased TB risk (aOR 0.8, 95% CI 0.3-2.0), whereas ever treatment with leflunomide (aOR 6.0, 95% CI 1.5-24.7), azathioprine (aOR 3.8, 95% CI 1.1-13.8), and prednisolone (PSL; aOR 2.4, 95% CI 1.0-6.0) was. There were no significant differences between maximum dose of PSL, treatment duration with PSL before TB, or cumulative dose of PSL the year before TB diagnosis between cases and controls. Obstructive pulmonary disease was associated with an increased TB risk (aOR 3.9, 95% CI 1.5-10.7). CONCLUSION: Several RA-associated factors may contribute to increased TB risk in biologic-naïve patients with RA, making the risk of TB activation difficult to predict in the individual patient. To further decrease TB in patients with RA, the results suggest that screening for latent TB should also be considered in biologic-naïve patients.
33128201 Epidemiology and Treatment of Patients with Rheumatoid Arthritis, Psoriatic Arthritis and 2021 Jan INTRODUCTION: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (PSO) are chronic inflammatory diseases that have a substantial impact on patients' health. This retrospective database study aimed to assess the epidemiology, comorbidities, diagnosis and treatment patterns of RA, PsA and PSO in the German population. METHODS: Data were extracted from the Deutsche Forschungsdatenbank für Abrechnungsinformationen der Krankenversicherung database from 2012 to 2016 for patients aged ≥ 18 years holding full health coverage in the reporting year at least. Diagnoses were defined according to International Classification of Diseases (ICD)-10 codes. Reported outcomes included prevalence and incidence rates, pre-defined comorbidities, diagnosing and treating physicians, and treatment exposure. A subgroup analysis was performed for women of childbearing age (females aged 18-45 years). RESULTS: The prevalence rates of RA, PsA and PSO in Germany were consistent over the study period; by 2016 they were 0.4%, 0.3% and 2.1%, respectively, and in women of childbearing age they were 0.2%, 0.2% and 1.5%, respectively. RA, PsA and PSO were predominantly observed among patients aged > 45 years. RA and PsA were more prevalent in women, while PSO had an approximately equal gender distribution. Depressive episodes were the most frequently reported comorbidity in 2016 (RA: 25.7%; PsA: 25.1%; PSO: 17.8%), and this was similar in women of childbearing age (RA: 20.5%; PsA: 23.4%; PSO: 16.3%). Approximately 50% of patients with RA and PsA and 6% of patients with PSO were receiving systemic treatment in 2016, of which methotrexate (RA: 38.4%; PsA: 30.2%; PSO: 2.2%) was most common. Biologic therapies were the least frequently used treatment options (RA: 28.9%; PsA: 20.9%; PSO: 1.8%). CONCLUSIONS: This analysis provides key epidemiological information for patients with RA, PsA and PSO, including in women of childbearing age, in Germany and highlights common comorbidities and that patients were likely receiving insufficient treatment for these diagnoses.