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ID PMID Title PublicationDate abstract
27062373 The role of radiology in the quantification of digital ulnar deviation in rheumatoid arthr 2016 Jun BACKGROUND: Rheumatoid arthritis (RA) is a common inflammatory polyarthritis, which causes functional digital ulnar deviation (UD). Radiographic and magnetic resonance imaging (MRI) assessment of the hands is essential in RA, but its role in the quantification of UD remains unclear. PURPOSE: To compare UD measurements in RA patients between clinical goniometric assessments versus standardized radiographs and MRI. METHODS: Fifteen RA patients with clinically apparent UD and 11 RA patients without UD underwent a rheumatological examination prior to recruitment to this study. Goniometric measurements for UD at the metacarpophalangeal (MCP) joints were performed by an occupational therapist (OT). Standardized hand radiographs, and MRI studies of the dominant hand using 3T MRI scanner with 16 channel hand/wrist coil were evaluated. Angulation measurements for radiographs and MRI were performed independently by two experienced musculoskeletal radiologists who were blinded to the rheumatologist's, occupational therapist's and each other's assessments. RESULTS: Inter-observer correlation between radiologists was >0.97 for both radiographic and MRI measurements. Correlation between OT goniometric measurements and the imaging-based measurements was limited at 0.496 for radiographs and 0.317 for MRI. Correlation between imaging modalities was 0.513. Compared to OT measurements, radiographic and MRI study measurements significantly underestimate the angulation in RA patients with UD (P < 0.001). CONCLUSIONS: The results of this study demonstrated discordance between radiological and goniometric measurements of digital ulnar angulation at the MCP joints in RA patients. Although imaging plays a key role in understanding structural damage and disease activity in RA, it should be emphasized that radiological measurements underrate joint malalignment.
27311189 [Recent advances in upper extremity surgery for rheumatoid arthritis]. 2016 Jun The number of cases with rheumatoid arthritis who requires arthroscopic synovectomy is declining, but it is still a useful procedure in combination with effective pharmacologic disease control. For the destruction of glenohumeral joint, total shoulder arthroplasty is effective for pain relief and functional outcome for patients without rotator cuff impairment. The reverse shoulder arthroplasty has been shown favorable short-term results, but need a careful indication for rheumatoid shoulder with poor bone stock and bone quality. Linked or unlinked total elbow arthroplasty are now reliable methods for the reconstruction of rheumatoid elbows with acceptable long-term survival. Joint replacement surgery for proximal interphalangeal joint is a challenging procedure in terms of relatively high complication rate and disappointing improvement in range of motion, whereas achieves good patients' satisfaction for pain relief and improved finger appearances.
26114379 Morning stiffness response with delayed-release prednisone after ineffective course of imm 2015 OBJECTIVE: To assess morning stiffness in rheumatoid arthritis (RA) patients switched from immediate-release (IR) to delayed-release (DR) prednisone. METHOD: Circadian Administration of Prednisone in Rheumatoid Arthritis-1 (CAPRA-1) is a 12-week, randomized, multicentre, active-controlled study of morning stiffness that consisted of a double-blind phase and a 9-month open-label extension. Patients receiving IR prednisone with no significant improvement after the double-blind study were switched to DR prednisone. Morning stiffness duration and median absolute and relative changes in pain and global assessment were evaluated (3, 6, and 9 months). RESULTS: In patients switched from IR to DR prednisone (n=110), statistically significant reductions in morning stiffness occurred over 3 months and were sustained for 9 months. Absolute reduction of morning stiffness was ~50 min with >40% relative reduction at each visit. Interleukin (IL)-6 levels were reduced by the same amount. Statistically significant and clinically meaningful mean reductions in morning stiffness were maintained at >67 min at each visit along with significant improvements in pain and patient global assessment. There was no evidence of tachyphylaxis seen over the 9-month study. CONCLUSIONS: Patients receiving disease-modifying anti-rheumatic drugs (DMARDs) and IR prednisone who had not had significant reductions in morning stiffness demonstrated statistically significant and clinically meaningful improvements when switched to DR prednisone.
24092415 A weighted genetic risk score using all known susceptibility variants to estimate rheumato 2015 Jan BACKGROUND: There is currently great interest in the incorporation of genetic susceptibility loci into screening models to identify individuals at high risk of disease. Here, we present the first risk prediction model including all 46 known genetic loci associated with rheumatoid arthritis (RA). METHODS: A weighted genetic risk score (wGRS) was created using 45 RA non-human leucocyte antigen (HLA) susceptibility loci, imputed amino acids at HLA-DRB1 (11, 71 and 74), HLA-DPB1 (position 9) HLA-B (position 9) and gender. The wGRS was tested in 11 366 RA cases and 15 489 healthy controls. The risk of developing RA was estimated using logistic regression by dividing the wGRS into quintiles. The ability of the wGRS to discriminate between cases and controls was assessed by receiver operator characteristic analysis and discrimination improvement tests. RESULTS: Individuals in the highest risk group showed significantly increased odds of developing anti-cyclic citrullinated peptide-positive RA compared to the lowest risk group (OR 27.13, 95% CI 23.70 to 31.05). The wGRS was validated in an independent cohort that showed similar results (area under the curve 0.78, OR 18.00, 95% CI 13.67 to 23.71). Comparison of the full wGRS with a wGRS in which HLA amino acids were replaced by a HLA tag single-nucleotide polymorphism showed a significant loss of sensitivity and specificity. CONCLUSIONS: Our study suggests that in RA, even when using all known genetic susceptibility variants, prediction performance remains modest; while this is insufficiently accurate for general population screening, it may prove of more use in targeted studies. Our study has also highlighted the importance of including HLA variation in risk prediction models.
26028000 Methotrexate-associated Lymphoproliferative Disease with Multiple Pulmonary Nodules in a P 2015 Patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) sometimes develop lymphoproliferative disease (LPD). MTX-associated LPD can affect nodal or extranodal sites, including the gastrointestinal tract, skin, lungs, kidneys and soft tissues, at almost equal frequency. However, it is very rare for MTX-associated LPD to manifest as multiple nodules in the lungs. We herein report the case of a RA patient who developed MTX-associated LPD with multiple pulmonary nodules during a 5-year course of MTX therapy.
25418136 Expression of choline and acetylcholine transporters in synovial tissue and cartilage of p 2015 Feb Increasing evidence is showing that the non-neuronal cholinergic system plays an important role in the pathology of rheumatoid arthritis (RA). Choline transport into the cell is the rate-limiting step for the synthesis of acetylcholine (ACh), which can be released directly or in vesicles from the cell. However, in the human joint little is known about choline import or the release of ACh from the cell. Thus, we analyze the expression of members of the organic cation transporter (OCT), of the newly discovered choline transporter-like (CTL) family and of classical neuronal components such as the high-affinity choline transporter (CHT1) and the vesicular ACh transporter (VAChT) in the synovium and cartilage of the human hip joint from patients with osteoarthritis (OA) and RA. OCT1, OCT3 and OCTN1 and all members of the CTL family were expressed in synovial and cartilage samples. The expression of CTL1 and CTL2 was localized in synovial macrophages and fibroblasts. CHT1 mRNA expression was detectable only in the synovium, whereas VAChT was completely absent in all samples. Therefore, in the human joint, choline transport into the cell and the release of ACh seems to be mediated mainly by members of the OCT and CTL family. Expression of transporters appears not to be influenced by the pathological state, as no differences have been detected between joints from OA or RA patients. Importantly, however, all necessary components for choline import and the release of non-neuronal ACh are present in the human joint.
27057749 Targeted delivery of low-dose dexamethasone using PCL-PEG micelles for effective treatment 2016 May 28 Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block-poly (ε-caprolactone) (PCL-PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL-PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL-PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders.
26657273 Pharmaceutical potential of tacrolimus-loaded albumin nanoparticles having targetability t 2016 Jan 30 Albumin is considered an attractive dug carrier for hydrophobic drugs to target inflamed joints of rheumatoid arthritis. This study focused on the pharmaceutical potential of albumin-based nanoparticles (NPs) on delivery of tacrolimus (TAC) to enhance targetability and anti-arthritic efficacy. TAC-loaded human serum albumin (HSA) nanoparticles (TAC HSA-NPs) were prepared using the nab™ technology. The resulting NPs were 185.8 ± 6.8 nm in diameter and had a zeta potential value of -30.5 ± 1.1 mV, as determined by dynamic light scattering. Particles were uniformly spherical in shape as determined by transmission electron microscopy. The encapsulation efficacy of TAC was 79.3 ± 3.7% and the water solubility was over 46 times greater than that of free TAC. TAC was gradually released from NPs over 24h, which is sufficient time for targeting and treatment of the NPs in inflamed arthritis via intravenous injection. In vitro study using splenocytes excised from spleens of mice following induction of arthritis using collagen clearly demonstrated the anti-proliferative activity of TAC HSA-NPs on activated T cells compared with non-activated T cells. Furthermore, TAC HSA-NPs displayed significantly more anti-arthritic activity than TAC formulations including intravenously administered TAC solution or oral TAC suspension, as reflected by the incidence of arthritis and clinical score (1.6 vs. 3.2 and 5.0, respectively). These improvements were due to the targetability of HSA that facilitated the accumulation of TAC HSA-NPs at inflamed arthritis sites. TAC HSA-NPs are a promising drug delivery system to enhance water solubility and increase accumulation in joints for treatment of rheumatoid arthritis.
27419896 B Cell Lymphoma mimicking Rheumatoid Arthritis. 2016 Non Hodking´s lymphoma (NHL) may involve bones but synovial involvement is uncommon. We describe a patient who presented with polyarthritis, sicca symptoms and rash suggestive of rheumatoid arthritis. An atypical skin rash prompted skin and synovial biopsies. A diagnosis of synovial and skin malignant large B-cell lymphoma anaplastic subtype was performed. Chemotherapy with dexamethasone, vincristine and rituximab was started. Following treatment the patient had complete resolution of cutaneous and articular lymphoma manifestations.
26611549 Glucocorticoids and Rheumatoid Arthritis. 2016 Feb Glucocorticoids (GCs) were discovered in the 1940s and were administered for the first time to patients with rheumatoid arthritis in 1948. However, side effects were subsequently reported. In the last 7 decades, the mechanisms of action for both therapeutic properties and side effects have been elucidated. Mechanisms for minimizing side effects were also developed. GCs are the most frequently used class of drugs in the treatment of rheumatoid arthritis because of their efficacy in relieving symptoms and their low cost. A review of clinical applications, side effects, and drug interactions is presented.
26642431 Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthr 2015 Dec 4 Rheumatoid arthritis (RA) and osteoarthritis (OA), two common types of arthritis, affect the joints mainly by targeting the synovium and cartilage. Increasing evidence indicates that a significant network connects synovitis and cartilage destruction during the progression of arthritis. We recently demonstrated that hypoxia-inducible factor (HIF)-2α causes RA and OA by regulating the expression of catabolic factors in fibroblast-like synoviocytes (FLS) or chondrocytes. To address the reciprocal influences of HIF-2α on FLS and chondrocytes, we applied an in vitro co-culture system using a transwell apparatus. When co-cultured with HIF-2α-overexpressing chondrocytes, FLS exhibited increased expression of matrix metalloproteinases and inflammatory mediators, similar to the effects induced by tumor-necrosis factor (TNF)-α treatment of FLS. Moreover, chondrocytes co-cultured with HIF-2α-overexpressing FLS exhibited upregulation of Mmp3 and Mmp13, which is similar to the effects induced by interleukin (IL)-6 treatment of chondrocytes. We confirmed these differential HIF-2α-induced effects via distinct secretory mediators using Il6-knockout cells and a TNF-α-blocking antibody. The FLS-co-culture-induced gene expression changes in chondrocytes were significantly abrogated by IL-6 deficiency, whereas TNF-α neutralization blocked the alterations in gene expression associated with co-culture of FLS with chondrocytes. Our results further suggested that the observed changes might reflect the HIF-2α-induced upregulation of specific receptors for TNF-α (in FLS) and IL-6 (in chondrocytes). This study broadens our understanding of the possible regulatory mechanisms underlying the crosstalk between the synovium and cartilage in the presence of HIF-2α, and may suggest potential new anti-arthritis therapies.
27247203 Is rituximab an effective treatment of refractory calcinosis? 2016 May 31 Calcinosis, the deposition of calcified material in soft tissues, is frequently seen in systemic sclerosis and dermatomyositis. Treatment options are limited, with disappointing results. Some recent case reports suggest that rituximab may be an attractive therapeutic option. In case 1, a 54-year-old woman who presented with rheumatoid arthritis in association with scleromyositis was treated with rituximab for rheumatoid arthritis. Despite this, she developed multiple progressive calcinosis, necessitating extracorporeal shock wave lithotripsy to limit calcinosis extension and pain. In case 2, a 38-year-old man, previously treated for an anti-Pm/Scl-positive polymyositis/scleroderma overlap syndrome, presented with multiple tumoural periarticular calcinosis, which progressed despite bisphosphonates, sodium thiosulfate and thalidomide. We decided to start rituximab. Progression of calcinosis was still evident 6 and 12 months after anti-CD20 treatment. Many treatments have been tried to treat calcinosis without demonstrated effectiveness. Presently, rituximab cannot be recommended for this indication in the absence of successful controlled trials.
26844284 Collagen Specific T-Cell Repertoire and HLA-DR Alleles: Biomarkers of Active Refractory Rh 2015 Dec Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and associates with HLA-DRB1*04. The Collagen IIp261-273-specific T cell repertoire in the peripheral blood of DR4 + patients at the onset of the disease shows a restricted TCR-beta chain usage among which the most frequent is TRBV25. To define whether this group of DR4-restricted collagen-specific shared T cell could represent markers of active-severe disease and response to therapy, 90 subjects affected by early-RA were enrolled in the study; peripheral blood mononuclear cells were cultured with or without the human collagen II peptide p261-273 and were examined by immunoscope analysis for the usage of the previously identified shared TCR-beta chains. We report that the presence of T cells carrying rearrangement TRBV25 associated with HLA-DR haplotype and disease activity. HLA-DRB1* haplotypes 04-04, 04-01 and 04-11 were significantly associated with usage of TRBV25, higher disease activity at the onset of disease and poor response to DMARDs. Finally, the HLA-DRB1* haplotype appeared complementary with current serologic tools to predict good and poor responders in a treat to target strategy. The data reported here offer clues to predict the course of the disease and to foresee personalized treatments in RA patients.
25877498 A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with 2015 Jun OBJECTIVE: To evaluate the efficacy and safety of brodalumab, a human monoclonal antibody inhibitor of the interleukin 17 receptor, in subjects with rheumatoid arthritis (RA). METHODS: Patients (n = 252) with inadequate response to methotrexate (MTX) were randomized to receive subcutaneous injections of brodalumab (70 mg, 140 mg, or 210 mg) or placebo. The primary endpoint was the American College of Rheumatology 50% response (ACR50) at Week 12. RESULTS: Demographics and baseline characteristics were generally balanced among treatment groups. At Week 12, ACR50 occurred in 16% (70 mg), 16% (140 mg), 10% (210 mg), and 13% (placebo; all nonsignificant vs placebo) of subjects. No significant treatment effects were observed for the secondary endpoints, including ACR20, ACR70, and Disease Activity Score in 28 joints. Incidences of all adverse events (AE), including serious AE (SAE), were similar across treatment groups. A total of 7 subjects reported SAE during the study (2 in the placebo group and 5 in the brodalumab groups), none of which was treatment related. There was 1 death (cardiopulmonary failure) ∼1 week after the last dose in the 140 mg group. CONCLUSION: Our study failed to find evidence of meaningful clinical efficacy with brodalumab treatment in subjects with RA who had an inadequate response to MTX. These preliminary results do not support further evaluation of brodalumab as a treatment for RA. Clinicaltrials.gov number: NCT00950989.
26032077 [Single nucleotide polymorphism of miR-149 and susceptibility of rheumatoid arthritis]. 2015 May OBJECTIVE: To investigate the association between microRNA (miR)-149 polymorphism and susceptibility to rheumatoid arthritis (RA ), as well as the clinical characteristics in patients with RA . METHODS: A total of 200 RA patients and 120 healthy controls were recruited from Department of Rheumatology and Immunology of Nanjing First Hospital. After obtaining the informed consent, we collected 2 mL of anti-coagulated venous blood samples from all studied subjects to isolate the whole blood genomic DNA, and the clinical data were collected as well. Single nucleotide polymorphisms of miR-149 rs22928323 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Correlation between single nucleotide polymorphisms and clinical features were compared. RESULTS: The frequencies of TT, TC and CC for rs22928323 of miR-149 were 25.3%, 51.1% and 23.6% or 18.3%, 20.0% and 61.7% in the patients or the healthy controls, respectively. The onset risk of allele C in RA patients was increased compared with allele T [OR=1.38, 95% CI (1.01-1.75), P=0.023]. There were no significant difference in rheumatoid factor, blood urine nitrogen, antikeratin antibody, and other clinical characteristics among the 3 genotypes in RA patients (P>0.05). CONCLUSION: SNP rs22928323 in miR-149 is correlated with RA in the east of Chinese Han population, whereas there is no correlation between miR-149 polymorphism and clinical characteristics in patients with RA.
25602858 Golimumab, the newest TNF-α blocker, comes of age. 2015 Jul Golimumab, a fully human monoclonal antibody against tumour necrosis factor-α (TNF-α) is one of the newest biologics that has become available for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Following the initial randomised double-blind placebo-controlled clinical trials, which demonstrated the efficacy and safety of the drug in the context of a limited patient sample and a relatively short time frame, golimumab has been the focus of continuous investigation through the extensions of the above-mentioned trials, new clinical trials and registries of biologic drug use in daily clinical practice. The review of this data and their inclusion in meta-analyses and indirect comparisons across TNF-α blockers suggest that golimumab possesses similar properties regarding efficacy and safety as the older monoclonal anti-TNF-α antibodies. The novelty of golimumab is perhaps its dosing regimen, i.e. subcutaneous self-administration once monthly, which allows for the least disturbance in the life of patients.
26627986 Small molecules with anti-inflammatory properties in clinical development. 2016 Jan Inflammation is a crucial physiological response of our body to any kind of noxa be it an infection or tissue injury. However, this physiological process can be detrimental if dysregulated, and when the acute inflammatory response fails to resolve the cause of inflammation, there can be a switch to chronification. According to ICD 10 (WHO) over 3.000 diseases exist with the suffix "-itis" which terms an inflammatory disease. For the treatment of inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widespread drugs while glucocorticoids are among our strongest weapons against inflammation, making them emergency treatments for acute episodes of chronic inflammation. For the treatment of many inflammatory disorders, both are not satisfying. Consequently, industrial and academic research on anti-inflammatory drugs is very intensive. In this review, we evaluate current treatments and unmet needs of chronic inflammatory diseases with high prevalence (rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disease, inflammatory bowel disease, and psoriasis), and systematically review small molecules with anti-inflammatory properties presently in clinical trials for the aforementioned diseases. As the pathophysiological knowledge of diseases increased over the last decades, a more specific intervention of inflammatory pathways becomes possible. After one hundred years of NSAIDs and over fifty years of glucocorticoids, more specific drugs for anti-inflammatory therapy such as roflumilast or fingolimod are rising. The aim of this article is to critically review the literature on small anti-inflammatory molecules in clinical trials to generate an idea of what we can expect in the future.
27442114 Rheumatoid Arthritis Disease Activity Is Determinant for ABCB1 and ABCG2 Drug-Efflux Trans 2016 OBJECTIVE: To compare drug efflux function of ABCB1 and ABCG2 transporters in rheumatoid arthritis (RA) patients with active disease and in remission. METHODS: Twenty two active RA patients (DAS28 ≥3.2) and 22 patients in remission (DAS28<2.6) were selected from an early RA clinic. All patients were evaluated at study inclusion and six months later. ABCB1 and ABCG2 functional activity was measured in peripheral lymphocytes by flow cytometry. The percentage of cells able to extrude substrates for ABCB1 and ABCG2 was recorded. RESULTS: Active patients had higher ABCB1 and ABCG2 activity compared with patients in remission (median [interquartile range]): 3.9% (1.4-22.2) vs (1.3% (0.6-3.2), p = 0.003 and 3.9% (1.1-13.3) vs 0.9% (0.5-1.9) p = 0.006 respectively. Both transporters correlated with disease activity assessed by DAS28, rho = 0.45, p = 0.002 and rho = 0.47, p = 0.001 respectively. Correlation was observed between the time from the beginning of treatment and transporter activity: rho = 0.34, p = 0.025 for ABCB1 and rho = 0.35, p = 0.018 for ABCG2. The linear regression model showed that DAS28 and the time from the onset of treatment are predictors of ABCB1 and ABCG2 functional activity, even after adjustment for treatment. After six months we calculated the correlation between change in DAS28 and change in the functional activity in both transporters and found a moderate and significant correlation for ABCG2 (rho = 0.28, p = 0.04) and a non-significant correlation for ABCB1 (rho = 0.22, p = 0.11). CONCLUSIONS: Patients with active RA have an increased function of ABCB1 and ABCG2, and disease activity is the main determinant of this phenomena.
27384149 Rapid improvement of Clinical Disease Activity Index (CDAI) at 3 months predicts a prefera 2016 Sep OBJECTIVES: To investigate whether the Clinical Disease Activity Index (CDAI) at three months predicts a preferable CDAI outcome at one year in patients with active rheumatoid arthritis (RA) treated with tocilizumab (TCZ). METHODS: Seventy-eight RA patients in the Nagasaki Prefecture, Japan, whose disease activities at baseline were moderate to high as estimated by the CDAI and who had received 8 mg/kg of TCZ every four weeks, were consecutively enrolled in this study from April 2008 to March 2011. The association of the CDAI at three months with that at one year was examined by the Cochran-Armitage test. The variables at baseline and at three months that were predictive of remission or low disease activity (LDA) according to the CDAI at one year were assessed by logistic regression analysis. RESULTS: Most of the patients (40 out of 44: 91%), whose CDAI at three months showed remission or LDA continued to show remission or LDA at one year. Disease activity at three months significantly correlated with the frequency of LDA or remission at one year (p<0.0001). Logistic regression analysis revealed that only remission or LDA at three months as determined by the CDAI was predictive of remission or LDA at one year as determined by the CDAI (odds ratio 33.2, p<0.0001). CONCLUSIONS: A preferable clinical outcome as estimated by the CDAI at one year in active RA patients treated with TCZ is predicted by the CDAI at three months, suggesting that the treat-to-target strategy carried out using the CDAI can be used in clinical practice in these patients.
26990778 Smoking-Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Coh 2016 Nov OBJECTIVE: To investigate the association between smoking status and smoking cessation with mortality in patients with rheumatoid arthritis (RA). METHODS: An incident cohort of patients with RA was identified using the Clinical Practice Research Datalink, a database of UK primary care electronic medical records. Time-varying smoking status, years of cessation, and amount smoked were determined from patients' medical records. The date and underlying cause of death were identified by linkage with Office for National Statistics records. The associations between smoking status and smoking cessation with all-cause and cause-specific mortality (circulatory disease, all cancers, lung cancer, respiratory disease, and respiratory infection) were investigated using adjusted Cox (all-cause mortality) and Fine-Gray (cause-specific mortality) regression. RESULTS: The cohort comprised 5,677 patients (median age 61.4 years, 68% women), with 40% as never smokers, 34% former smokers, and 26% current smokers at baseline. Compared to never smoking, current smoking was associated with an increased risk of all-cause mortality (hazard ratio 1.98 [95% confidence interval (95% CI) 1.56, 2.53]), and mortality due to circulatory disease (subdistribution hazard ratio [SHR] 1.96 [95% CI 1.33, 2.90]) and lung cancer (SHR 23.2 [95% CI 5.15, 105]). Each year of smoking cessation was associated with a decreased risk of all-cause mortality (former heavy smokers SHR 0.85 [95% CI 0.77, 0.94], former light smokers SHR 0.90 [95% CI 0.84, 0.97]). CONCLUSION: Current smoking is associated with an increased risk of all-cause, cardiovascular, and lung cancer mortality in patients with RA. Each year of cessation is associated with a reduced risk of all-cause mortality. This information may prove helpful in smoking cessation programs for patients with RA.