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Summary: An 82-year-old woman with a 60-year history of a lung tumor presented with hypoglycemia. Non-islet cell tumor hypoglycemia (NICTH) was suspected; however, her hypoglycemia stabilized with supplemental food. She was discharged, based on her wishes, and planned to undergo surgery later. After discharge, the hypoglycemia worsened rapidly and required immediate resection. Postoperatively, the hypoglycemia resolved. Western immunoblot analysis confirmed the presence of big insulin-like growth factor 2, confirming NICTH. This patient experienced the rapid progression of symptoms after an unprecedentedly long-term asymptomatic state. Therefore, when NICTH is suspected, early intervention is recommended regardless of the presence of asymptomatic state. Learning points: In patients with NICTH, the onset of hypoglycemia is usually within a year of tumor detection, and few reports regarding long-term asymptomatic NICTH have been documented. NICTH can cause rapidly progressive symptoms after a long-term asymptomatic state, as in this case, and an asymptomatic state does not preclude the necessity for intervention, especially when patients are at risk for malnutrition. Tumor resection is the only curative treatment for patients with NICTH, but there is no consensus regarding the timing of surgery. However, considering the possibility of rapid symptom progression, patients should be examined and treated in a timely manner.
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BACKGROUND: Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA. METHODS: We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan-Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model. RESULTS: Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001). CONCLUSIONS: In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.
Subject(s)
Arthritis, Rheumatoid , Azetidines , Janus Kinase Inhibitors , Piperidines , Purines , Pyrazoles , Sulfonamides , Humans , Arthritis, Rheumatoid/drug therapy , Male , Female , Middle Aged , Janus Kinase Inhibitors/therapeutic use , Janus Kinase Inhibitors/adverse effects , Azetidines/therapeutic use , Azetidines/adverse effects , Retrospective Studies , Aged , Pyrazoles/therapeutic use , Pyrazoles/adverse effects , Purines/therapeutic use , Purines/adverse effects , Sulfonamides/therapeutic use , Sulfonamides/adverse effects , Piperidines/therapeutic use , Piperidines/adverse effects , Pyrimidines/therapeutic use , Pyrimidines/adverse effects , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Triazoles/therapeutic use , Triazoles/adverse effects , Risk Factors , Adult , PyridinesABSTRACT
This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan-Meier's curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan-Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.
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Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis without severe myositis but with characteristic cutaneous manifestations and severe interstitial lung disease. Joint symptoms can occur in patients with anti-MDA5 antibody-positive CADM. However, the treatment strategy and utility of ultrasound for treating joint symptoms remain unknown. We herein report an 85-year-old man with anti-MDA5 antibody-positive CADM who presented with ultrasound-confirmed synovitis that improved with medium-dose corticosteroid therapy.
Subject(s)
Autoantibodies , Dermatomyositis , Interferon-Induced Helicase, IFIH1 , Synovitis , Ultrasonography , Humans , Dermatomyositis/drug therapy , Dermatomyositis/immunology , Dermatomyositis/diagnostic imaging , Dermatomyositis/complications , Male , Interferon-Induced Helicase, IFIH1/immunology , Aged, 80 and over , Synovitis/drug therapy , Synovitis/diagnostic imaging , Synovitis/etiology , Synovitis/immunology , Autoantibodies/blood , Autoantibodies/immunology , Adrenal Cortex Hormones/therapeutic use , Treatment OutcomeABSTRACT
Objective: This study aimed to compare the incidence rates (IRs) of infections, including herpes zoster (HZ), in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) or interleukin-6 inhibitors (IL-6is). Methods: We retrospectively analyzed 444 RA patients treated using IL-6is (n = 283) or JAKis (n = 161). After adjusting for clinical characteristic imbalances by propensity score matching (PSM), we compared the IRs of infections including HZ between the JAKi and IL-6i groups. Results: Observational period: 1423.93 patient years (PY); median observational period: 2.51 years. After PSM, incidence rate ratios comparing JAKi with IL-6i were 3.45 (95% confidence interval [CI]: 1.48-9.04) for serious infections other than HZ indicating that the JAKi-treated group was more likely to develop serious infection than the IL-6i-treated group. Multivariate Cox regression analyses revealed that the use of prednisolone > 5.0 mg/day, coexisting interstitial lung disease (ILD), and diabetes mellitus (DM) were independent risk factors for serious infections. The crude IR for HZ was significantly higher in the JAKi group, but the difference between groups was not significant (IRR: 2.83, 95% CI: 0.87-10.96) in PSM analysis. Unadjusted and PSM analyses performed in our study showed increased IRs of serious infections in patients with RA treated with JAKis compared with those treated with IL-6is. Conclusions: The presence of ILD or DM and the use of prednisolone were found to be independent risk factors for serious infection in RA patients treated using JAKis. Whereas the IRs for HZ after PSM were not significantly different between the JAKi and IL-6i groups.
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Diabetes is a risk factor for thyroid cancer development. Serum thyroglobulin (Tg) levels are useful as sensitive and specific tumor markers for monitoring radioiodine (RAI)-refractory thyroid cancer; however, the impact of glycemic control on serum Tg levels is poorly understood. Here, we present a case of a female patient with lung metastases of RAI-refractory thyroid cancer in whom glycemic control may have influenced the serum Tg levels. Despite receiving thyroid-stimulating hormone suppression therapy, her serum Tg levels remained elevated. Subsequently, she developed type 2 diabetes and was administered antidiabetic medications for 6 years. Throughout the course of diabetes management, her serum Tg levels fluctuated according to the level of glycemic control, showing a strong correlation with her hemoglobin A1c levels (r = 0.92, P < .01). Similar to the serum levels of other tumor markers, such as the carcinoembryonic antigen and carbohydrate antigen 19-9, the serum levels of Tg can be influenced by glycemic control. Therefore, serum Tg levels in patients with RAI-refractory thyroid cancer and diabetes should be monitored with attention to glycemic control.
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Globally, the rapid aging of the population is predicted to become even more severe in the second half of the 21st century. Thus, it is expected to establish a growing expectation for innovative, non-invasive health indicators and diagnostic methods to support disease prevention, care, and health promotion efforts. In this study, we aimed to establish a new health index and disease diagnosis method by analyzing the minerals and free amino acid components contained in hair shaft. We first evaluated the range of these components in healthy humans and then conducted a comparative analysis of these components in subjects with diabetes, hypertension, androgenetic alopecia, major depressive disorder, Alzheimer's disease, and stroke. In the statistical analysis, we first used a student's t test to compare the hair components of healthy people and those of patients with various diseases. However, many minerals and free amino acids showed significant differences in all diseases, because the sample size of the healthy group was very large compared to the sample size of the disease group. Therefore, we attempted a comparative analysis based on effect size, which is not affected by differences in sample size. As a result, we were able to narrow down the minerals and free amino acids for all diseases compared to t test analysis. For diabetes, the t test narrowed down the minerals to 15, whereas the effect size measurement narrowed it down to 3 (Cr, Mn, and Hg). For free amino acids, the t test narrowed it down to 15 minerals. By measuring the effect size, we were able to narrow it down to 7 (Gly, His, Lys, Pro, Ser, Thr, and Val). It is also possible to narrow down the minerals and free amino acids in other diseases, and to identify potential health indicators and disease-related components by using effect size.
Subject(s)
Amino Acids , Hair , Humans , Hair/chemistry , Male , Amino Acids/analysis , Amino Acids/metabolism , Female , Middle Aged , Adult , Alopecia/diagnosis , Aged , Minerals/analysis , Minerals/metabolism , Alzheimer Disease/diagnosis , Alzheimer Disease/metabolism , Stroke , Hypertension , Depressive Disorder, Major/diagnosis , Diabetes Mellitus/diagnosis , Case-Control StudiesABSTRACT
OBJECTIVES: We aimed to evaluate the effects of age on clinical characteristics and outcomes in biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD)-naïve patients with rheumatoid arthritis (RA). METHODS: We analysed the cases of 234 Japanese b/tsDMARD-naïve RA patients who underwent b/tsDMARD treatment in a multicentre ultrasound prospective observational cohort. We compared the clinical characteristics at baseline and outcomes at 12 months between those aged ≥60 years and those <60 years. RESULTS: Compared to the <60-year-old group (n = 78), the ≥60-year-old group (n = 156) had higher inflammatory marker values and ultrasound combined scores, especially wrist joints, at baseline. Age at baseline positively correlated significantly with the ultrasound scores at baseline; however, age was not a significant variable by the multiple regression analysis. The patients treated with different MOAs in the ≥60-year-old group had comparable outcomes and multiple regression analysis revealed that mechanism of action (MOA) was not a significant contributor to the Clinical Disease Activity Index at 12 months. CONCLUSIONS: RA patients with advanced age demonstrated distinctive clinical characteristics. The MOAs were not associated with clinical outcomes and ultrasound outcomes in RA patients with advanced age.
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Systemic lupus erythematosus (SLE) is often seen with antiphospholipid antibody syndrome (APS), and these conditions may occur concurrently with severe immune thrombocytopenia (ITP) and even acute kidney injury (AKI); however, post-renal AKI due to bleeding is uncommon. Here, we describe a case of post-renal AKI and anuria in a patient with SLE and APS, which were attributable to urinary tract obstruction due to massive blood clots caused by secondary ITP. A 50-year-old Japanese woman was admitted to our hospital with anuria, abdominal tenderness, purpura in the trunk and in both legs, and severe thrombocytopenia. She had been receiving medical treatment for APS and SLE till the age of 45 years. Computed tomography revealed a blood clot without extravasation in both urinary tracts, and she was diagnosed with post-renal AKI due to complete obstruction of the urinary system. Additionally, based on her medical history, elevated platelet-associated Immunoglobulin G (IgG) levels, and increased megakaryocyte count, she was diagnosed with secondary ITP complicated by SLE and APS. She also had elevated APS-related autoantibodies, including antiphosphatidylserine/prothrombin Immunoglobulin M (IgM), and IgG. However, concomitant serositis such as lupus enteritis or cystitis was not seen. She was treated with a combination of glucocorticoids, intravenous immunoglobulin, and continuous haemodialysis/haemofiltration, which resulted in rapid improvement of her symptoms and renal dysfunction. Secondary ITP-induced massive bleeding of urinary tract can cause post-renal AKI. Appropriate diagnosis and aggressive treatment are necessary to improve prognosis in such patients.
Subject(s)
Acute Kidney Injury , Lupus Erythematosus, Systemic , Humans , Female , Middle Aged , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/diagnosis , Thrombocytopenia/etiology , Thrombocytopenia/diagnosis , Thrombocytopenia/complications , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Thrombosis/etiology , Thrombosis/diagnosis , Treatment OutcomeABSTRACT
OBJECTIVE: Glucocorticoids are effective in treating rheumatoid arthritis (RA) when used appropriately considering the balance of the risks and benefits, especially at low doses. We aimed to evaluate the response of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients having already been treated with glucocorticoids. METHODS: We reviewed RA patients treated with b/tsDMARDs in a prospective multicenter ultrasound cohort study. We compared the differences in the clinical characteristics at baseline and outcomes at 12 months between the two groups having been treated with and without glucocorticoids at baseline. The differences in the clinical characteristics and the treatments were balanced by the inverse probability weighting (IPW) with the propensity score. RESULTS: Of 307 patients with RA, 160 patients were treated with glucocorticoids at baseline. The median dose of glucocorticoids was equivalent to 5.0 mg/day of prednisolone. Significant differences were in age and concomitant methotrexate use, composite measures for the disease activity, and the ultrasound grayscale score at baseline. Patients treated with glucocorticoids had less frequent remissions defined by composite measures and ultrasound findings than those treated without glucocorticoids. These significant differences in the achievement of remissions remained robust even after adjusting differences in the clinical characteristics and the treatments between the two groups by IPW. CONCLUSION: RA patients treated with glucocorticoids had a higher disease activity at baseline and a poorer response to treatments with b/tsDMARDs than those without glucocorticoids. The states of patients requiring glucocorticoids might be associated with the poor response to the b/tsDMARDs.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Glucocorticoids/adverse effects , Cohort Studies , Prospective Studies , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Methotrexate/therapeutic use , Antirheumatic Agents/adverse effects , Multicenter Studies as TopicABSTRACT
Coronavirus disease 2019 (COVID-19) is a respiratory viral disease, and several cases of autoimmune diseases have been reported after infection. This report presents the case of a 38-year-old Japanese woman who developed systemic lupus erythematosus (SLE) following COVID-19. Clinical manifestations included dermatological complications, joint pain, and positive autoantibodies. The patient met the SLE classification criteria, and renal involvement was observed. Her symptoms improved with immunosuppressive therapy. A literature review identified 10 similar cases, those with lymphopenia and renal involvement. SLE should be considered in patients with persistent nonspecific symptoms after COVID-19 infection, particularly when hematologic and renal involvement are present.
Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Female , Adult , COVID-19/complications , COVID-19/diagnosis , Immunosuppressive Agents/therapeutic use , SARS-CoV-2ABSTRACT
The complement component C5a contributes to the recruitment of immune cells to inflamed tissues and local inflammation. The proinflammatory cytokine interleukin (IL)-1ß is also related to inflammatory disorders through inflammasome activation. However, the association between inflammasome activation and C5a is unclear. Human peripheral blood mononuclear cells (PBMCs) were stimulated with C5a and measured for IL-1ß secretion by enzyme-linked immunosorbent assay (ELISA). The pro-IL-1ß expression in cell lysates was also examined by Western blot analysis. Similarly, magnetic bead-isolated CD14+ monocyte-depleted and lymphocyte-depleted PBMCs were stimulated with C5a, and immunoblot analysis was performed using an anti-cleaved-IL-1ß (p17) antibody. FACS was performed to detect caspase-1-activated cells. C5a-stimulated PBMCs produced IL-1ß in C5a concentration-dependent manner. The protein levels of pro-IL-1ß in the cell lysates were significantly increased. Furthermore, the cleaved-IL-1ß (p17) was faintly detected in the same lysates. Active caspase-1 was demonstrated in C5a-simulated CD14+ monocytes by FACS. Cleaved-IL-1ß (p17) was demonstrated in the supernatant of C5a-stimulated PBMCs. Lymphocyte-depleted PBMCs stimulated with C5a but monocyte-depleted PBMCs produced cleaved-IL-1ß (p17). C5a induced the production of mature IL-1ß in PBMCs. The IL-1ß production is mediated mainly by caspase-1 activation in CD14+ monocytes. These results suggest that C5a alone potentiates mature IL-1ß production mainly in monocytes.
Subject(s)
Caspase 1 , Complement C5a , Interleukin-1beta , Leukocytes, Mononuclear , Humans , Interleukin-1beta/metabolism , Caspase 1/metabolism , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/immunology , Inflammasomes/metabolism , Inflammasomes/immunology , Monocytes/immunology , Monocytes/metabolism , Cells, Cultured , Lipopolysaccharide Receptors/metabolism , Enzyme ActivationABSTRACT
This study evaluated the real-world effectiveness of belimumab (BLM) in the treatment of systemic lupus erythematosus (SLE) patients with moderate to high disease activity. This retrospective cohort study enrolled 129 Japanese patients with moderate to high SLE disease activity who received BLM between January 2013 and March 2023. The clinical outcomes, including the flare-free survival, SLE Disease Activity Index 2000 (SLEDAI-2K) score, and prednisone-equivalent dose, in the BLM and mycophenolate mofetil (MMF) treatment groups were compared before and after treatment. Safety data for BLM were collected. Additionally, we compared the effectiveness of BLM and intravenous cyclophosphamide (IV-CY) treatment using the stabilized inverse probability of treatment weighting (IPTW) method based on the propensity scores. This observational study enrolled 129 patients with moderate/severe SLE: 48 patients received belimumab, 45 received IV-CY, and 36 received MMF and prednisolone for remission induction therapy. The median follow-up for the BLM group was 17.0 months. Among them, 19 received BLM plus MMF. BLM significantly reduced the mean SLEDAI-2K (from mean baseline to 52 weeks: 49.2% reduction from 12.8 to 6.5) and prednisone daily dose (from mean baseline to 52 weeks: 21.9% reduction from 12.8 to 10.0 mg/day). The flare-free survival at 52 weeks was not significantly different between the BLM and MMF groups. There was no significant difference in the flare-free survival rates or reduction rates of the SLEDAI-2K between the patients treated with BLM and those treated with BLM plus MMF. In the propensity score-matched comparative analyses, there was no significant difference in the flare-free survival rates or an estimated decline in the SLEDAI-2K scores between the patients with lupus treated with BLM and IV-CY. BLM may be a promising alternative treatment option for lupus patients with moderate or high disease activity who do not respond to conventional treatments.
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Background: To investigate the clinical features of Japanese patients with Familial Mediterranean Fever (FMF), we evaluated the frequency of attacks, treatment responses, and adverse effects in 27 patients with FMF treated with colchicine or canakinumab in a real-world clinical setting. Methods: We retrospectively reviewed 27 Japanese patients with FMF treated at our institute between April 2012 and June 2023. All patients were diagnosed with FMF according to the Tel-Hashomer criteria. We performed genetic analyses of the MEFV gene using targeted next-generation sequencing. The clinical response was monitored through the number of attacks, and inflammatory markers were monitored through the C-reactive protein (CRP), and serum amyloid A (SAA) concentrations. Colchicine resistance was defined as the presence of at least one attack/month despite administration of the maximum tolerated dose of colchicine for at least 6 months, and C-reactive protein and serum amyloid A levels above the normal range between attacks. Results: A total of 27 patients diagnosed with FMF were enrolled in this study and the median follow-up period was 36.4 months. The median attack frequency was 1.0 (interquartile range: 0.33-1.0) every 3 months before treatment initiation. All the patients (n = 27) were treated with colchicine. Among the 27 patients, 20 (71.8%) showed a clinical response and 7 (25.9%) showed an incomplete response with sufficient doses of colchicine (n = 5) and non-sufficient doses (n = 2). Two patients on non-sufficient doses were unable to increase colchicine to the maximum dose due to diarrhea and liver dysfunction. All seven patients achieved a reduction in attack frequency after the initiation of canakinumab. No serious adverse events associated with canakinumab treatment were observed. In these seven patients with colchicine-resistant FMF (crFMF), the MEFV exon 10 variant was not detected, and the absence ratio of the MEFV variant was significantly higher compared to those without crFMF. Conclusions: Colchicine was effective in 71.8% (20/27) of Japanese patients with FMF; however, the remaining patients (7/27) had crFMF. Canakinumab effectively controlled febrile attacks in crFMF, even in the absence of pathogenic MEFV exon 10 variants.
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Background: The ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis. Methods: We retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups. Results: After PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67-7.42) for malignancy and 3.03 (95% CI: 0.77-15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23-2.97). Conclusion: The IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Interleukin-6 Inhibitors , Janus Kinase Inhibitors , Neoplasms , Humans , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Interleukin-6 Inhibitors/adverse effects , Interleukin-6 Inhibitors/therapeutic use , Janus Kinase Inhibitors/adverse effects , Janus Kinase Inhibitors/therapeutic use , Neoplasms/chemically induced , Retrospective StudiesABSTRACT
The articular involvement in patients with familial Mediterranean fever (FMF) represents a clinical characteristic of acute monoarthritis with pain and hydrarthrosis, which always resolves spontaneously. Colchicine prevents painful arthritis attacks in most FMF cases. Spondyloarthritis is rarely associated with Japanese patients with FMF. Here, we report a Japanese male patient with FMF-related axial joint involvement. A 43-year-old male Japanese patient who presented with recurrent febrile episodes with hip joint and back pain was referred to our hospital. He carried heterozygous variants in exon 2 (L110P/E148Q) of the MEFV gene. FMF was suspected, and oral administration of colchicine (1 mg/day) was initiated. Colchicine treatment improved his febrile attack with hip joint pain. He was diagnosed as having FMF based on the Tel-Hashomer diagnostic criteria for FMF since he fulfilled one major criterion (repeated febrile attack accompanied by hip joint pain) and one minor criterion (improvement with colchicine treatment). Although the human leucocyte antigen-B27 allele was not detected, sacroiliitis-related symptoms progressed despite the ongoing colchicine treatment. Salazosulphapyridine and methotrexate were administered in addition to colchicine; however, these treatments were not effective. Canakinumab treatment successfully resolved this unique aspect of sacroiliitis, and the patient was finally diagnosed with FMF-associated axial joint involvement.
Subject(s)
Familial Mediterranean Fever , Sacroiliitis , Humans , Male , Adult , Familial Mediterranean Fever/complications , Familial Mediterranean Fever/diagnosis , Familial Mediterranean Fever/drug therapy , Colchicine/therapeutic use , Sacroiliitis/diagnosis , Sacroiliitis/drug therapy , Sacroiliitis/etiology , Japan , Fever , Arthralgia , Pyrin/geneticsABSTRACT
BACKGROUND: We examined the real-world drug retention rate and safety data of Janus kinase inhibitors (JAKis) in elderly patients with rheumatoid arthritis (RA). METHODS: This study enrolled 133 RA patients (≥65 years) with sufficient clinical data who were initiated with JAKis during the study period. These patients were divided into two groups: the very elderly group (≥ 75 years) and the elderly group (65 ≤ years < 75). The drug retention rates of JAKis were compared using Kaplan-Meier curves. RESULTS: The discontinuation rates of JAKis were as follows: lack of effectiveness 27 (20.3%), adverse events (AEs) 29 (21.8%), and remission 2 (1.5%). There was no significant difference in the overall drug retention rate between the very elderly group (≥75 years) and the elderly group. Furthermore, the overall drug retention rates of JAKis were not affected by gender, methotrexate use, and anti-citrullinated protein/peptide antibody (ACPA) status. The discontinuation rates of JAKis due to AEs were comparable both in the very elderly group (≥75 years) and the elderly group (65 ≤ years < 75). Whereas chronic lung disease and hypoalbuminemia were independently associated with discontinuation rates due to AEs, the overall drug retention rates were significantly lower in patients treated with the approved dose of JAKis than in those treated with a reduced or tapered dose. CONCLUSIONS: Our results suggest that the overall drug retention rate of JAKis in very elderly patients (≥75 years) was comparable with that in elderly patients (65 ≤ years < 75). The discontinuation rates of JAKis due to AEs were also comparable both in very elderly group patients and elderly patients.
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OBJECTIVES: To determine whether drug-induced lymphocytopenia is associated with drug retention rates of JAKi (tofacitinib or baricitinib) in rheumatoid arthritis (RA) patients. METHODS: Patients with RA who were initiated with tofacitinib (n = 38) or baricitinib (n = 74) between July 2015 and July 2022 and continued for at least 4 months were enrolled in this study. Absolute lymphocyte count (ALC) value was obtained pre-treatment and monthly after initiation of JAKi (up to 4 months). Associations between ALC nadir at an early phase (up to 4 months) from JAKi initiation and drug retention rates were analysed. RESULTS: 112 patients (87 females; age, 71.2 ± 14.0 years; disease duration, 9.2 ± 10.5 months; DAS28-CRP, 3.60 ± 1.12; DAS28-ESR, 4.43 ± 1.29; CDAI, 17.9 ± 12.9; C-reactive protein, 3.07 ± 3.43 mg/dL; and lymphocyte count, 1361.9 ± 538.7 per µL) treated with tofacitinib or baricitinib were retrospectively analysed. Lymphocytopenia (>10% decline in lymphocyte count to pre-treatment basal levels) was observed in a quarter of RA patients treated with JAKi (tofacitinib; 16 baricitinib; 14). RA patients with lymphopenia were associated with the lower drug retention rates of tofacitinib compared to those without lymphocytopenia. The reduced drug retention rates in patients with lymphocytopenia were attributed to the discontinuation of tofacitinib due to AEs. Whereas lymphocytopenia was not associated with lower drug retention rates of baricitinib. Pre-treatment absolute lymphocyte counts did not affect the drug retention rates of JAKi in patients with RA. CONCLUSIONS: These findings suggest that lymphopenia during the first 4 months from the initiation of JAKi is associated with reduced drug retention rates in patients with RA due to AEs, which is exclusively associated with the use of tofacitinib.
ABSTRACT
Temporal arteritis (TA) is a large-vessel vasculitis mostly seen in older patients. Amyloid A (AA) amyloidosis secondary to a chronic inflammation induces multiple organ dysfunctions, including a dysfunction of the gastrointestinal tract. Herein, we present a case of TA complicated by AA amyloidosis that was resistant to oral and intravenous steroids. An 80-year-old man with a history of new-onset headache, jaw claudication, and distended temporal arteries was referred to our department. On admission, the patient presented with tenderness and a subcutaneous temporal nodule in both temple arteries. Ultrasonography of the nodule revealed an anechoic perivascular halo surrounding the right temporal artery. Following the diagnosis of TA, high-dose prednisolone therapy was initiated. However, the patient presented with recurrent abdominal pain and refractory diarrhea. Due to the unclear origin of refractory diarrhea, an extensive workup, including biopsy of the duodenal mucosa, was performed. Endoscopy revealed chronic inflammation in the duodenum. Immunohistochemical analysis of duodenal mucosal biopsy samples revealed AA amyloid deposition resulting in the diagnosis of AA amyloidosis. After tocilizumab (TCZ) administration, refractory diarrhea reduced; however, the patient died of intestinal perforation 1 month after the start of TCZ administration. Gastrointestinal involvement was the main clinical manifestation of AA amyloidosis in the present case. This case highlights the importance of bowel biopsy screening for amyloid deposition in patients with unexplained gastrointestinal tract symptoms, even in a recent onset of large-vessel vasculitis. In the present case, the carriage of the SAA1.3 allele likely contributed to the rare association of AA amyloidosis with TA.