Predicting Disease Activity in Rheumatoid Arthritis With the Fibromyalgia Survey Questionnaire: Does the Severity of Fibromyalgia Symptoms Matter?

OBJECTIVE: To determine if the degree of baseline fibromyalgia (FM) symptoms in patients with rheumatoid arthritis (RA), as indicated by the Fibromyalgia Survey Questionnaire (FSQ) score, predicts RA disease activity after initiation or change of a disease-modifying antirheumatic drug (DMARD). METHODS: One hundred ninety-two participants with active RA were followed for 12 weeks after initiation or change of DMARD therapy. Participants completed the FSQ at the initial visit. The Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) was measured at baseline and follow-up to assess RA disease activity. We evaluated the association between baseline FSQ score and follow-up DAS28-CRP. As a secondary analysis, we examined the relationship between the 2 components of the FSQ, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), with follow-up DAS28-CRP. Multiple linear regression analyses were performed, adjusting for clinical and demographic variables. RESULTS: In multiple linear regression models, FSQ score was independently associated with elevated DAS28-CRP scores 12 weeks after DMARD initiation (B = 0.04, P = 0.01). In secondary analyses, the WPI was significantly associated with increased follow-up DAS28-CRP scores (B = 0.08, P = 0.001), whereas the SSS was not (B = -0.03, P = 0.43). CONCLUSION: Higher levels of FM symptoms weakly predicted worse disease activity after treatment. The primary factor that informed the FSQ's prediction of disease activity was the spatial extent of pain, as measured by the WPI.

Reported Pericardial Toxicities Associated with Acute Myelogenous Leukemia Treatments: A Pharmacovigilance Analysis of the FDA Adverse Reporting Database.

Acute myelogenous leukemia (AML) is one of the most common leukemias experienced in adults and conveys significant morbidity and mortality. While the traditional anthracycline based treatments of AML involves cytarabine, developments in alternatives (liposomal cytarabine, fludarabine, cladribine, azacitidine, decitabine), and targeted agents (midostaurin, gilteritinib, enasidenib, ivosidenib, gemtuzumab ozogamicin, and venetoclax) exist. Multiple cardiovascular adverse events, notably pericardial toxicity, have been observed in small studies; however, to date little is known about the comparative pericardial toxicity among these newer regimens. Due to the paucity of data, we sought to investigate the reported pericardial events and mortality associated with treatments for AML. Utilizing the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we identified all adverse events associated with FDA approved treatments for AML (2002-2022). Pericardial events were defined as pericarditis, pericardial effusion and tamponade. We excluded any individuals with age <18 years old. Logistic regression was utilized to identify factors associated with pericardial events. Out of 94,262 reported adverse events, 675 pericardial toxicities were included (243 pericarditis, 479 tamponade). Pericardial events occurred less often in Cladribine (0.3%, P < 0.001), fludarabine (0.4%, P < 0.001), Venetoclax (0.3%, P < 0.001), enasidenib (0.3%, P value < 0.001), and ivosidenib (0.3%, P < 0.001) compared to Cytarabine (0.9%). Tamponade events occurred significantly less often in cladribine (0.1%, P < 0.001), fludarabine (0.4%, P = 0.001), enasidenib (0.1%, P = 0.006), ivosidenib (0.1%, P = 0.01), and venetoclax (0.1%, P < 0.001) compared to cytarabine 0.7%. After adjusting for age and sex, Cladribine (reporting odds ratio [ROR] 0.35 [95% CI 0.18-0.68], P = 0.008) and Fludarabine (ROR 0.65 [0.45-0.92], P = 0.03), venetoclax (ROR 0.57 [0.41-0.79], P < 0.001) remained significantly associated with lower incidence of reported pericardial events. While cytarabine has been the routinely used and/or drug of choice for induction chemotherapy for AML, alternatives like cladribine may have a greater safety profile regarding pericardial toxicities. Future studies should be directed at further investigating cardiovascular safety profiles of AML induction therapy.

Correlation of Fibromyalgia Survey Questionnaire and Quantitative Sensory Testing Among Patients With Active Rheumatoid Arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) commonly demonstrate disordered pain processing associated with high pain sensitization. Pain sensitization is often assessed using quantitative sensory testing (QST), which is burdensome to patients. The self-administered Fibromyalgia Survey Questionnaire (FSQ) has been proposed as a low-burden, surrogate measure of central pain sensitization. We examined the correlation between FSQ and QST in patients with active RA. METHODS: Participants in the Central Pain in Rheumatoid Arthritis (CPIRA) cohort underwent FSQ and QST evaluation at enrollment. QST measures included pressure pain threshold (PPT) at the thumb, trapezius, wrist, and knee; temporal summation (TS) at the wrist and arm; and conditioned pain modulation (CPM). Partial Spearman correlation between FSQ and each QST measure was assessed, adjusted for demographic factors, study site, disease characteristics, and pain catastrophizing. Sensitivity analyses included (1) stratified analysis by sex and (2) evaluation of how each component of FSQ associates with the QST measures. RESULTS: Among 285 participants with active RA, FSQ was weakly but statistically significantly correlated with PPT (r range = -0.31 to -0.21), and TS (r range = 0.13-0.15) at all sites in unadjusted analyses. After adjustment, statistically significant correlations persisted for TS at the wrist and PPT at all sites (except the thumb). Sensitivity analyses did not identify differences in association based on sex or with individual FSQ components. CONCLUSION: FSQ and QST were correlated among participants with active RA, but the strength of association was weak. QST and FSQ are not interchangeable measures of pain sensitization.

Proportionate Cardiovascular Mortality in Chronic Inflammatory Disease in Adults in the United States From 1999 to 2019.

BACKGROUND: Despite a rising prevalence of chronic inflammatory disease (CID), the recent trends in cardiovascular disease (CVD) mortality of patients with CID is scarce. In this study, we investigated patterns of CVD mortality in systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) compared with the general population. METHODS: We used the 1999 to 2019 multiple causes of death files from the national center for health statistics to analyze patterns and trends of proportionate CVD mortality in CID compared with the general population. RESULTS: We analyzed a total of 11,154 CVD deaths in IBD, 58,337 CVD deaths in RA, 6227 CVD deaths in SLE, and 17,826,871 CVD deaths in the general population. Between 1999 and 2019, we found that proportionate CVD mortality decreased significantly in the IBD group (25% to 16%), RA group (34% to 25%), and the general population (41% to 31%), but did not change for the SLE group (15% to 15%). Patients with SLE who died of CVD were approximately 10 years younger compared with CVD decedents with RA, IBD, or general population. The White population had higher proportionate CVD mortality than African American (IBD [19% vs 16%-18%] and SLE [14%-16% vs 12-14%], respectively). CONCLUSIONS: This study identifies current trends in CVD mortality in the CID population and elucidates current demographics in CVD mortality in CID. Although proportionate CVD mortality decreased in the general population, and in patients with RA and IBD, there was no change among patients with SLE. Further studies are needed to elucidate these differences.

Fibromyalgianess and glucocorticoid persistence among patients with rheumatoid arthritis.

OBJECTIVES: Over one-third of patients with RA exhibit evidence of fibromyalgianess, which is associated with higher rates of disability and inadequate responsiveness to RA treatment. Patients with RA often remain on glucocorticoids long-term, despite the known risk of dose-dependent morbidity. We undertook this study to examine the relationship between fibromyalgianess and glucocorticoid persistence among RA patients. METHODS: We followed participants with active RA on oral prednisone for ∼3 months after initiating a new DMARD. Fibromyalgianess was measured using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key FM features often superimposed upon RA. Severity of fibromyalgianess was stratified as follows: FSQ <8 low, FSQ 8-10 moderate and FSQ >10 high/very high. The association between baseline fibromyalgianess and glucocorticoid persistence, defined as prednisone use at 3-month follow-up visit after DMARD initiation, was assessed using multiple logistic regression adjusted for baseline demographics, RA duration, serostatus and inflammatory activity assessed using swollen joint count and CRP. RESULTS: Of the 97 participants on prednisone at baseline, 65% were still taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent glucocorticoid use, compared with 84% of participants with high or very high fibromyalgianess. After adjustment for non-inflammatory factors and inflammatory activity, participants with high/very high baseline fibromyalgianess were more likely to be taking prednisone at follow-up relative to those with low fibromyalgianess [odds ratio 4.99 (95% CI 1.20, 20.73)]. CONCLUSION: High fibromyalgianess is associated with persistent glucocorticoid use, independent of inflammatory activity.

Association of Dysregulated Central Pain Processing and Response to Disease-Modifying Antirheumatic Drug Therapy in Rheumatoid Arthritis.

OBJECTIVE: To determine the association between dysregulated central pain processing and treatment response in rheumatoid arthritis (RA). METHODS: One hundred eighty-two participants with active RA were followed up for 12 weeks after starting a disease-modifying antirheumatic drug (DMARD). To assess central pain processing, participants underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at the trapezius muscles, temporal summation, and conditioned pain modulation (CPM). QST measures were categorized as high central dysregulation versus low central dysregulation. The association between baseline central dysregulation and treatment response, as defined by the European League Against Rheumatism (EULAR) response criteria, was assessed using multiple logistic regression adjusted for demographic characteristics, RA-related variables, and psychosocial variables. RESULTS: A good EULAR response was achieved in fewer participants with high CPM dysregulation than participants with low CPM dysregulation (22.5% versus 40.3%; P = 0.01). A similar trend, though not significant, was noted when central dysregulation was assessed with PPT and temporal summation. The adjusted odds ratios (ORs) for the association between high central dysregulation and good EULAR response were 0.59 for PPTs (95% confidence interval [95% CI] 0.28-1.23), 0.60 for temporal summation (95% CI 0.27-1.34), and 0.40 for CPM (95% CI 0.19-0.83). In a model examining the combined effects of dysregulated temporal summation and CPM, dysregulation of both measures was associated with lower odds of achieving a good EULAR response (OR 0.23 [95% CI 0.07-0.73]). CONCLUSION: Low CPM was significantly associated with lower odds of achieving a good EULAR response, suggesting that inefficient descending inhibitory mechanisms may be a potential treatment target for further study.

Association of Pain Centralization and Patient-Reported Pain in Active Rheumatoid Arthritis.

OBJECTIVE: Pain is a significant burden for patients with rheumatoid arthritis (RA) despite advancements in treatment. We undertook this study to examine the independent contribution of pain centralization to the pain experience of patients with active RA. METHODS: A total of 263 RA patients with active disease underwent quantitative sensory testing (QST), including assessment of extraarticular pressure pain thresholds (PPTs), temporal summation (TS), and conditioned pain modulation (CPM). The pain experience was assessed by a pain intensity numeric rating scale and the Patient-Reported Outcomes Measurement Information System pain interference computerized adaptive test. We examined associations between QST measures and pain intensity and pain interference. Multiple linear regression models were adjusted for demographic and clinical variables, including swollen joint count and C-reactive protein level. RESULTS: Patients with the lowest PPTs (most central dysregulation) reported higher pain intensity than patients with the highest PPTs (adjusted mean difference 1.02 [95% confidence interval (95% CI) 0.37, 1.67]). Patients with the highest TS (most central dysregulation) had higher pain intensity than those with the lowest TS (adjusted mean difference 1.19 [95% CI 0.54, 1.84]). CPM was not associated with differences in pain intensity. PPT and TS were not associated with pain interference. Patients with the lowest CPM (most centrally dysregulated) had lower pain interference than patients with the highest CPM (adjusted mean difference -2.35 [95% CI -4.25, -0.44]). CONCLUSION: Pain centralization, manifested by low PPTs and high TS, was associated with more intense pain. Clinicians should consider pain centralization as a contributor to pain intensity, independent of inflammation.