Abstract:Combined infliximab and methotrexate treatment improves the depressive state in rheumatoid arthritis patients more effectively than methotrexate alone Abstract Objective: Rheumatoid arthritis (RA) patients have a greater depressive tendency than normal subjects, and infliximab is known to provide quick therapeutic effects and to have high bioavailability for RA. We therefore investigated whether the depressive state of RA patients would be improved by infliximab.Material and Methods: The Self-Rating Depression… Show more
“…Faecal calprotectin, conversely, indexes neutrophil infiltration into gastro-intestinal (GI) mucosal tissue and is the noninvasive gold standard for indexing inflammation of the gastrointestinal mucosa in IBD, reflecting mucosal inflammation in Crohn’s Disease (CD) more accurately than C-reactive protein or clinical scores such as the Crohn’s Disease Activity Index (CDAI) [ 19 , 20 ]. Treatment with anti-TNFα, a widely used therapy in patients with IBD[ 21 ], effectively modulates immune function in the gastrointestinal tract, and appears to reduce sickness behavior and depressive symptoms in IBD [ 22 , 23 ], rheumatoid arthritis [ 24 ] and psoriasis [ 25 ].…”
BackgroundIn inflammatory bowel disease (IBD), immune activation with increased circulating TNF-α is linked to the intensity of gastrointestinal symptoms and depression or anxiety. A central feature of depression is cognitive biases linked to negative attributions about self, the world and the future. We aimed to assess the effects of anti-TNFα therapy on the central processing of self-attribution biases and visceral afferent information in patients with Crohn’s disease.MethodsWe examined 9 patients with Crohn’s disease (age 26.1±10.6. yrs, 5 female, 5 ileocolonic, 2 colonic and 2 ileal disease) during chronic anti-TNFα therapy (5 adalimumab, 4 infliximab). Patients were studied twice in randomized order before and after anti-TNFα administration. On each occasion patients underwent functional magnetic resonance imaging (fMRI) of the brain during a test of implicit attribution biases regarding sickness/health and undertook a standardized nutrient challenge.ResultsFollowing anti-TNFα treatment, ratings of ‘fullness’ following nutrient challenge reduced compared to pre-treatment ratings (p<0.05). Reaction times revealed improved processing of self-related and positive health words, consistent with improved implicit sense of wellbeing that correlated with improvements in sensory function after treatment (r = 0.67, p<0.05). Treatment-associated improvements in implicit processing were mirrored by alterations of prefrontal, amygdala, posterior cingulate and visual regions. Between patients, the degree of functional amygdala change was additionally explained by individual differences in attention regulation and body awareness rankings.ConclusionIn patients with Crohn’s disease, anti-TNFα administration reduces visceral sensitivity and improves implicit cognitive-affective biases linked to alterations in limbic (amygdala) function.
“…Faecal calprotectin, conversely, indexes neutrophil infiltration into gastro-intestinal (GI) mucosal tissue and is the noninvasive gold standard for indexing inflammation of the gastrointestinal mucosa in IBD, reflecting mucosal inflammation in Crohn’s Disease (CD) more accurately than C-reactive protein or clinical scores such as the Crohn’s Disease Activity Index (CDAI) [ 19 , 20 ]. Treatment with anti-TNFα, a widely used therapy in patients with IBD[ 21 ], effectively modulates immune function in the gastrointestinal tract, and appears to reduce sickness behavior and depressive symptoms in IBD [ 22 , 23 ], rheumatoid arthritis [ 24 ] and psoriasis [ 25 ].…”
BackgroundIn inflammatory bowel disease (IBD), immune activation with increased circulating TNF-α is linked to the intensity of gastrointestinal symptoms and depression or anxiety. A central feature of depression is cognitive biases linked to negative attributions about self, the world and the future. We aimed to assess the effects of anti-TNFα therapy on the central processing of self-attribution biases and visceral afferent information in patients with Crohn’s disease.MethodsWe examined 9 patients with Crohn’s disease (age 26.1±10.6. yrs, 5 female, 5 ileocolonic, 2 colonic and 2 ileal disease) during chronic anti-TNFα therapy (5 adalimumab, 4 infliximab). Patients were studied twice in randomized order before and after anti-TNFα administration. On each occasion patients underwent functional magnetic resonance imaging (fMRI) of the brain during a test of implicit attribution biases regarding sickness/health and undertook a standardized nutrient challenge.ResultsFollowing anti-TNFα treatment, ratings of ‘fullness’ following nutrient challenge reduced compared to pre-treatment ratings (p<0.05). Reaction times revealed improved processing of self-related and positive health words, consistent with improved implicit sense of wellbeing that correlated with improvements in sensory function after treatment (r = 0.67, p<0.05). Treatment-associated improvements in implicit processing were mirrored by alterations of prefrontal, amygdala, posterior cingulate and visual regions. Between patients, the degree of functional amygdala change was additionally explained by individual differences in attention regulation and body awareness rankings.ConclusionIn patients with Crohn’s disease, anti-TNFα administration reduces visceral sensitivity and improves implicit cognitive-affective biases linked to alterations in limbic (amygdala) function.
“…However, there is a lack of data on the effect of biologic agents on depression. A study conducted in Japan found that combined infliximab and methotrexate treatment was more effective in improving the depressive state of patients with RA compared with methotrexate alone . In a Taiwan cross-sectional study, authors found a significantly lower risk of depression among patients receiving etanercept compared with the nonbiologic group .…”
Section: Discussionmentioning
confidence: 99%
“…A study conducted in Japan found that combined infliximab and methotrexate treatment was more effective in improving the depressive state of patients with RA compared with methotrexate alone. 35 In a…”
ImportanceDepression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA.ObjectiveTo investigate the risk of depression following RA diagnosis among patients in South Korea.Design, Setting, and ParticipantsThis retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023.ExposuresSeropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more.Main Outcomes and MeasuresNewly diagnosed depression (ICD-10 codes F32 or F33).ResultsThe mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74]).Conclusions and RelevanceThis nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.
“…The up-regulation of TNF levels in depressed patients has been demonstrated, therefore, infliximab is used to treat depression also (Rani et al, 2022 ). In 2014, a clinical study involving 34 RA-associated depression patients showed that infliximab could reduce RA disease activity and improve symptoms of depression (Miwa et al, 2014 ). However, randomized controlled trials conducted in Canada and the United States showed that infliximab did not significantly reduce depression in adults with bipolar depression compared with a placebo (McIntyre et al, 2019 ).…”
Section: What Causes Depression In Ra Patients?mentioning
Depression is an independent mood disorder and one of the most common comorbidities of rheumatoid arthritis (RA). Growing evidence suggests that there is two-way regulation between RA and depression, resulting in a vicious cycle of RA, depression, poor outcomes, and disease burden. The rising prevalence of RA-associated depression warrants a re-examination of the relationships between them. Here we provide an overview of the etiology and pathological mechanisms of RA-associated depression, and recent advances in treatment with biologics, which will facilitate the development of new and effective prevention and treatment strategies.
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