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ID PMID Title PublicationDate abstract
35449681 Diffuse Large B-cell Lymphoma of the Tibia in a Patient With Longstanding Seropositive Rhe 2022 Mar There has been an observance of increased occurrence of malignant lymphomas in patients with rheumatoid arthritis (RA). The increased risk of lymphoproliferative disorders has been linked to the severity of RA disease activity, the use of disease-modifying agents like methotrexate and certain genetic links between RA and lymphomas. This article outlines the case of an 88-year-old gentleman with a 13-year history of seropositive rheumatoid arthritis on methotrexate who presented with ankle pain and was subsequently found to have diffuse large B-cell lymphoma on further workup.
35285489 Successful Switching Treatment of Adalimumab for Refractory Pyoderma Gangrenosum in a Pati 2022 Mar 12 Pyoderma gangrenosum (PG) is a rare chronic skin disease characterized by painful skin ulcers. There are no treatment guidelines for PG, but systemic treatments including biologics are often used. Recently, adalimumab (ADA), a fully human monoclonal antibody against tumor necrosis factor, was approved for refractory PG treatment in Japan. Herein, we report a case of rheumatoid arthritis with refractory PG two months after orthopedic surgery of the foot during treatment with low-dose etanercept and methotrexate. Although adding a moderate dose of glucocorticoid did not improve her PG, the patient showed a remarkable response after switching from etanercept to ADA in a higher dose than that used to treat rheumatoid arthritis. This higher dose of ADA may be effective for the treatment of refractory PG after the failure of another tumor necrosis factor inhibitors.
35464521 Methotrexate Pneumonitis After a Low-Dose Medication Error: A Case Report. 2022 Mar Methotrexate is recommended as the first choice of standard drug therapy following the diagnosis of rheumatoid arthritis. Pneumonitis related to methotrexate is a serious, unpredictable adverse event that may become life-threatening. We reported a case of a 68-year-old woman with rheumatoid arthritis that misunderstood the directions for use and took methotrexate daily, instead of weekly, leading to hepatic, hematological, and pulmonary toxicity.Although the histological evaluation was not performed, patient's clinical presentation, in addition to subsequent investigational findings, supported a diagnosis of pneumonitis resulting from MTX exposure. Toxic dosing over a long period of time along with the concomitant taking of pantoprazole and hypoalbuminemia could have increased the incidence of some adverse events. Concerning pneumonitis related to methotrexate, the toxic dose may have accelerated the pulmonary manifestations, but we do not know if correct dose had been taken, this adverse event would occur. This case enlightened two important issues in rheumatoid arthritis treatment: the possibility of medication errors and the rare, but potentially life-threatening, methotrexate-induced pneumonitis. Improving education and warnings when prescribing and dispensing low-dose methotrexate is essential.
35449774 Can SARS-CoV-2 infection trigger rheumatoid arthritis? A case report. 2022 Apr Inflammatory arthritis has been reported after SARS-COV-2 infection. We present a case of a 38-year-old female patient who developed polyarthralgia 1 month after SARS-COV-2 infection. Musculoskeletal examination was significant for synovitis of hands and wrists. Antinuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) antibodies were positive. Magnetic resonance imaging of the hands showed synovitis of the metacarpophalangeal joints and proximal interphalangeal joints of the hands, wrist joints, and tendinitis with tenosynovitis. The patient was diagnosed with seropositive nonerosive rheumatoid arthritis (RA) and initiated on therapy using nonsteroidal anti-inflammatory agents and disease-modifying anti-rheumatic drug methotrexate leading to an improvement in symptoms.
35145797 A Unique Interaction of Methotrexate and Nitrofurantoin Resulting in Irreversible Pulmonar 2022 Jan Pulmonary toxicity is the most well-known severe complication related to both methotrexate and nitrofurantoin, which can present as acute, subacute, and chronic. Rheumatoid arthritis is also known to cause pulmonary disease if left untreated. In this report, we present a unique case of a 94-year-old female being treated with methotrexate for several years and then treated with nitrofurantoin in the setting of rheumatoid arthritis and chronic urinary tract infections, resulting in irreversible pulmonary fibrosis, which can further cause more susceptibility to infections and pneumonia. Drug-drug interactions are common in polypharmacy and a patient's history should be analyzed thoroughly before prescribing any new medication that can cause more harm to the patient than good.
35453032 Treatment of early rheumatoid arthritis: Methotrexate and beyond. 2022 Jun For the last several decades, the standard of care for the initial management of rheumatoid arthritis (RA) has been methotrexate. Methotrexate is effective as monotherapy and in combination with conventional, biologic, and targeted-synthetic therapies. Methotrexate is generally well-tolerated, but has important, albeit uncommon, potential side-effects including a risk of liver toxicity and cytopenias. Some studies suggest that more active monitoring in patients with fatty liver disease may be appropriate. With reassuring safety data, more rapid dose escalation and use of subcutaneous therapy may provide even greater success. Some off-target benefits such as a reduction in cardiovascular disease risk have also been demonstrated, though these studies may suffer from confounding. Recent published guidelines continue to endorse methotrexate as first-line therapy. Methotrexate is a low-cost, safe, and effective therapy for RA that should not be overlooked nor too quickly abandoned.
35650123 A Case of Endothelial Damage-dominant Nephritis Related to IgA Vasculitis after 11 Years' 2022 May 31 A 43-year-old Japanese woman with rheumatoid arthritis treated by infliximab and methotrexate for 11 years was admitted for proteinuria and purpura. A kidney biopsy revealed endothelial damage-dominant nephritis with IgA deposition. Infliximab and methotrexate were discontinued, and tocilizumab was started; however, proteinuria persisted. Therefore, tocilizumab was discontinued, and oral prednisolone and methylprednisolone pulse therapy were administered. After 6 months, urinary protein was less than 0.1 g/day, and purpura subsided. To our knowledge, this is the first case of endothelial damage-dominant nephritis related to IgA vasculitis involving the skin and kidney after long-term use of infliximab and methotrexate.
35308233 Tofacitinib Decreases Autophagy of Fibroblast-Like Synoviocytes From Rheumatoid Arthritis 2022 The pathway of Janus tyrosine kinases (JAKs) has a central role in the pathogenesis of Rheumatoid Arthritis (RA) by regulating multiple immune functions and cytokine production. The JAK inhibitor tofacitinib is effective in RA patients not responding to methotrexate or TNF-inhibitors. Since hyperactive autophagy has been associated with impaired apoptosis of RA fibroblast-like synoviocytes (FLS), we aimed to investigate the role of tofacitinib in modulating autophagy and apoptosis in these cells. FLS isolated from RA biopsies were cultured with tofacitinib in presence of autophagy inducer rapamycin and in serum deprivation condition. Levels of autophagy, apoptosis, and citrullinated proteins were analyzed by western blot, flow cytometry, immunocytofluorescence, and Real-Time PCR. Rapamycin induced an increase in RA-FLS autophagy while the levels of autophagy marker LC3-II were reduced after in vitro treatment with tofacitinib. The analysis of autophagic flux by specific fluorescence dye confirmed the reduction of autophagy in RA FLS. The treatment with tofacitinib did not influence apoptosis of RA FLS. Modulation of the autophagic process by tofacitinib did not significantly change citrullination. The results of this study demonstrate that tofacitinib is able to modulate autophagy of FLS contributing to its effectiveness in RA patients.
35371839 Acute Pneumocystis jirovecii Pneumonia Due to Absolute Lymphopenia. 2022 Mar Pneumocystis pneumonia (PCP) is an opportunistic fungal infection associated with human immunodeficiency virus (HIV) infection as an acquired immunodeficiency syndrome (AIDS)-defining illness. The PCP incidence in patients with HIV has declined over the last few decades due to effective antiretroviral therapy and prophylaxis. The PCP incidence in HIV-negative patients has increased due to the increasing use of a wide array of immunosuppressants in cancer and autoimmune disease. PCP clinical course varies from patients with HIV in their clinical features, the severity of clinical presentation, and mortality. PCP in autoimmune diseases is rare, especially in rheumatoid arthritis (RA) in the United States of America (USA). Here, we describe an elderly Caucasian female with rheumatoid arthritis and left lung mucinous adenocarcinoma status post recent resection with no chemotherapy on a low dose of methotrexate (MTX) and prednisone presenting with acute hypoxic respiratory failure due to PCP from absolute lymphopenia.
35168508 Assessment of Rheumatoid Hand Function as a Characteristic Feature of Rheumatoid Arthritis 2022 Feb 15 BACKGROUND: The hand is an excellent work tool that provides the functional ability to mechanical work. The hand is affected in rheumatoid arthritis (RA) patients, it is a significant problem in the functional sphere as a result of deformities, the grasping function limitation and muscle strength. OBJECTIVES: The aim of the study was the assessment of grip strength, endurance and manipulation abilities of rheumatoid hands with or without deformities treated with methotrexate (MTX) or MTX plus biologics (MTX+BIO). MATERIAL AND METHODS: The study involved 80 RA women, (40 received MTX+BIO, 40 MTX), treated at the Rheumatology Department of the Central Clinical Hospital of Interior Affairs in Warsaw. VAS-pain, DAS28, SDAI, HAQ, HAQ hands, estimation of hand grip strength, endurance, manipulation ability were analyzed. RESULTS: In group MTX+BIO values of DAS28 (3.7±1.3 vs 4.3±1.2, p=0.019), HAQ (0.72 ± 0.57 vs 1.08± 0.87, p=0.011) and HAQ-hand (0.85±0.65 vs. 1.19±0.68, p=0.024) were statistically lower than in MTX group. Hand deformations recorded in 35 (43.7%) cases, 16 (40%) in MTX group, 19 (47.5%) in MTX+BIO. Comparison of grip strength, endurance, manipulation ability showed better results in MTX+BIO group with deformities (significance level from 0.013 to 0.046) than in MTX group. Relative differences in hand function in MTX + BIO group ranged from 10.8% (maximal power grip strength) to 127.6% (minimal hand endurance), after disease duration adjustment - from 28.2% (maximal power grip strength) to 148.4% (minimal hand endurance). CONCLUSION: Measuring grip strength, hand endurance, manipulation abilities are useful in RA patients with hand deformities.
35249916 A Case of Pneumonia and Meningoencephalitis Due to Varicella-zoster Virus Reinfection and 2022 Mar 5 A 72-year-old woman with rheumatoid arthritis was treated with methotrexate (MTX) and iguratimod. Upon examination of a liver tumor, blisters due to varicella-zoster virus (VZV) infection were observed. Despite oral administration of valacyclovir, she developed varicella pneumonia and meningoencephalitis. A VZV antibody test revealed reinfection. The liver tumor shrank after discontinuance of MTX, and polymerase chain reaction revealed the reactivation of the Epstein-Barr virus (EBV). Therefore, we were unable to deny MTX-associated lymphoproliferative disorder (MTX-LPD). This is the first case of a complication of pneumonia and meningoencephalitis due to VZV reinfection and EBV reactivation.
35165740 Seasonal Exacerbation of Rheumatoid Arthritis Detected by Big Claims Data Analysis: A Retr 2022 Feb 15 OBJECTIVES: The objective of the study was to determine the seasonal changes in the initiation of biological disease-modifying antirheumatic drugs (bDMARDs) and methotrexate (MTX) using big claims data. METHODS: We counted the monthly number of initial administrations of each bDMARD and MTX in patients with rheumatoid arthritis (RA) between April 2010 and March 2017. Data were collected from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). This database covers more than 95% of Japanese citizens. Seasonal changes in the number of initiations were determined. Patient claims were also classified according to drugs, districts, gender and ages. RESULTS: The initiation of bDMARDs and MTX administration varied according to the season in a sine curve shape, with the highest numbers in May to July and the lowest numbers in November to January. The same changing pattern was observed among each bDMARD, district, gender and age groups particularly when the number was on the higher side. CONCLUSION: We noted an apparent seasonal change in the number of bDMARDs initiated, with a peak during spring, suggesting an exacerbation of RA in the spring in Japan. These changes are overlooked in daily practice and are only visible using big data.
35640001 A Retrospective, Longitudinal Study of Rheumatoid Arthritis Treatment Patterns with Janus 2022 May 27 OBJECTIVES: There is limited information on the clinical use of Janus kinase inhibitors (JAKis) for rheumatoid arthritis (RA) treatment in Japan. The aim of this study was to identify disease-modifying antirheumatic drug (DMARD) treatment patterns in Japan. METHODS: This retrospective, longitudinal study extracted data from the Japan Medical Data Center database. Patients with RA diagnosis were enrolled 2016-2019, during which patients had a first prescription of a major DMARD, split into six mutually exclusive classes: methotrexate (MTX); other conventional synthetic (cs)DMARDs; tumor necrosis factor alpha (TNFα) inhibitors; cytotoxic T-lymphocyte-associated antigen-4-immunoglobulin; anti-interleukin-6 receptor therapies; and JAKis. The primary objective was to describe DMARD treatment patterns, especially for JAKis. RESULTS: Overall, 10,399 patients were included in the analysis. The most common treatments were MTX, other csDMARDs, and TNFα inhibitors. The total number of JAKi prescriptions increased approximately eight-fold during 2016-2019. Most (61.1%) patients who received JAKis had prior MTX or TNFα inhibitor treatment. JAKi treatment duration was longer than for biologics and other csDMARDs, and comparable to that of MTX. CONCLUSIONS: The sequence of drug class prescriptions for RA in Japan during 2016-2019 followed clinical guidelines. Over this period, JAKis were increasingly used as second-line treatment following MTX.
35636630 Development of pH-sensitive dextran-based methotrexate nanodrug for rheumatoid arthritis t 2022 May 27 Rheumatoid arthritis (RA) is a chronic and symmetrical autoimmune disease that primarily characterized with articular synovial hyperplasia, joint swelling, cartilage and bone destruction. The in-depth understanding of the role of immune signaling pathway inhibitors provides inspiration for the construction of new and more effective strategy for RA therapy. In this study, by loading methotrexate (MTX) into an acetalated dextran biopolymer, AcDEX, we developed a pH-sensitive, MTX-loaded and molecularly targeted nanodrug MTX@pH-AcDEX NPs) to decrease the toxicity of MTX and simultaneously enhance its therapeutic effect. The resultant MTX@pH-AcDEX NPs showed the spherical morphology and notable pH-responsiveness with high drug loading of 88.32%. As demonstrated in vitro and in vivo, the reduced cytotoxicity of both RAW264.7 cells and LPS-activated RAW264.7 cells treated with MTX@pH-AcDEX NPs was found compared to free MTX. Upon intravenous administration into adjuvant-induced arthritis (AIA) rat model, the nanodrug had potent pharmacokinetic and pharmacodynamic profiles, which can accumulate in RA lesions and release MTX inhibitors for regulating the JAK-STAT pathways. As a result, the MTX@pH-AcDEX NPs achieved the cartilage and bone protective and a better anti-inflammatory effect with negligible systemic toxicity, suggesting the strong potential of safe and effective nanodrug for RA therapy as well as other autoimmune diseases.
35600883 Huangqi Guizhi Wuwu Decoction Improves Arthritis and Pathological Damage of Heart and Lung 2022 Background: Huangqi Guizhi Wuwu Decoction (HGWD) is a traditional and effective Chinese medicine compound decoction for the treatment of rheumatoid arthritis (RA). However, there is few research on the treatment of rheumatoid cardiopulmonary complications. The present study was to study whether HGWD can alleviate the pathological changes caused by rheumatoid arthritis and cardiopulmonary complications. Methods: Five 3-month-old TNF-Tg mice were treated with HGWD (9.1 g/kg) once a day or the same dose of normal saline lasted for 8 weeks, and wild-type littermates of the same age were used as a negative control, and methotrexate (MTX) was intraperitoneally administered as a positive control. After the treatment, pathological staining was performed on the mouse ankle joints, heart, and lungs. Result: It was found that HGWD reduced the inflammation of the ankle joint synovium in TNF-Tg mice, and reduced myocardial hypertrophy, inflammatory infiltration and fibrosis of heart, as well as lung inflammation and fibrosis. Immunohistochemical staining with anti-TNF-α antibody showed that HGWD reduced the expression of TNF-α in the heart of TNF-Tg mice. Conclusion: In conclusion, HGWD alleviates joint inflammation in TNF-Tg mice and reduces the pathological changes of the heart and lungs.
35106597 Rheumatoid Arthritis Caused by Non-Tuberculous Mycobacteria Infection. 2022 Feb 1 A 72-year-old Japanese woman had right digital flexor tenosynovitis with a non-tuberculous mycobacteria (NTM) infection, which was identified as Mycobacterium marinum in culture. She had been treated at another hospital with clarithromycin, rifampicin, and ethambutol for the non-tuberculous tenosynovitis. However, the swelling of her right hand worsened, and 5 months later her left hand swelled and she exhibited symmetrical arthritis. Blood tests detected elevated serum C-reactive protein and rheumatoid factor positivity. Although rheumatoid arthritis (RA) was suspected and corticosteroid treatment was started, she came to our hospital because of the insufficient treatment effect. Musculoskeletal ultrasonography showed intra-articular and peritendinous power Doppler signal-positive symmetrical synovitis. A contrast-enhanced MRI evaluation of the left hand without NTM tenosynovitis revealed findings of inflammatory synovitis accompanied by bone marrow edema. We diagnosed RA and started treatment with weekly low-dose methotrexate pulses and 2 weeks of tocilizumab administration; her symptoms then disappeared within 2 months. This is a rare case of RA manifested with NTM-associated arthritis.
34797392 A flare of Still's disease following COVID-19 vaccination in a 34-year-old patient. 2022 Apr Vaccination is a cornerstone for reducing the risk of COVID-19 infection during a pandemic. Although the currently used COVID-19 vaccine is considered safe, some concerns persist regarding the likelihood of flares of rheumatic diseases. Still's disease is a rare auto-inflammatory disorder of unknown etiology, and the data on the flare of Still's disease following COVID-19 vaccination are limited. Therefore, we hereby present the case of a 34-year-old female patient with Still's disease who experienced a flare after a ChAdOx1 nCoV-19 vaccination. The patient visited the emergency department complaining of fever, arthralgia, myalgia, pleuritic chest pain and macular salmon-pink rash on her back for the past 2 days. She had maintained low Still's disease activity with etanercept and low-dose glucocorticoid for 14 years. She received the ChAdOx1 nCoV-19 vaccine 7 days before the flare. Laboratory investigations revealed leucocytosis and elevated serum levels of erythrocyte sedimentation rate, C-reactive protein, and ferritin. Computed tomography showed no specific findings. She received methylprednisolone pulse therapy, etanercept, and methotrexate for treating the Still's disease flare. However, her symptoms were not fully controlled, and she developed pericarditis, pleuritis, fever and macular rashes expanding to her extremities. After excluding infectious conditions by blood culture and pleural fluid analysis, we administered tocilizumab with methotrexate and prednisolone. Her symptoms and laboratory findings improved significantly, and she was discharged without symptoms 7 days later. Although rare, this case of a patient with Still's disease undergoing a flare following vaccination suggests that close observation of disease activity is warranted following COVID-19 vaccination.
35114930 Randomized clinical trials on the efficacy and safety of tocilizumab in subjects with rheu 2022 Feb 2 Background The current therapy of Rheumatoid Arthritis (RA) is confronted with many challenges such as inadequate response, infection, and treatment failure. Aim and objective The main objective was to assess the efficacy and safety of tocilizumab (TCZ) in subjects with RA using the available evidence from published randomized controlled trials. Methods The current systematic review was performed on nine randomized controlled trials from 2002 to 2016 for TCZ in subjects with rheumatoid arthritis. The primary outcomes were the clinical improvement in American College Rheumatology 20% (ACR20) or Disease Activity Score remission (DAS28), in addition to other outcomes such as ACR50 and ACR70 in the intention-to-treat population. Results We have conducted a systematic review on nine randomized controlled trials, with 4129, [100%] enrolled, of which 3248 [78.7%] were on the intention-to-treat. 2147 (66.1%) were treated with TCZ and 1101 (33.9%) have had received placebo or methotrexate or other conventional Disease-Modifying Anti-rheumatic Drugs (cDMARD) or biologic Disease-Modifying Anti-rheumatic Drugs (bDMARDs). In subjects taking TCZ with or without concomitant methotrexate, compared to placebo, subjects treated with TCZ 4 or 8 mg/kg were substantially and statistically significantly more likely than placebo or methotrexate to achieve the ACR20 and/or DAS28. There were no statistically significant differences in serious adverse events such as serious infection; however, subjects on TCZ were more likely to have increased lipid profile. Conclusion TCZ mono-therapy or in combination with methotrexate is valuable in diminishing rheumatoid arthritis disease activity and improving disability. Treatment with TCZ was associated with a significant surge in cholesterol levels, but no serious adverse effects. Randomized clinical trials with safety as primary outcome are warranted to report these safety issues.
35445719 Pharmacokinetics, Pharmacodynamics and Safety of Single-Dose Subcutaneous Sarilumab With o 2022 Apr 21 OBJECTIVES: To assess safety and pharmacokinetics (PK) of single-dose subcutaneous (SC) sarilumab or tocilizumab SC ± methotrexate; to assess pharmacodynamics (PD) of sarilumab SC or tocilizumab SC monotherapy in Japanese rheumatoid arthritis (RA) patients. METHODS: TDU13402 was a randomized, double-blind, placebo-controlled, single-ascending dose Phase 1 study (NCT01850680). Twenty-four patients (6 per treatment group) received sarilumab 50, 100, or 200 mg plus methotrexate or placebo (2 per cohort) on Day (D) 1; PK and safety were assessed through D57. PDY14191 was a randomized, open-label, single-dose study (NCT02404558). Thirty patients (15 per arm) received sarilumab 150 mg or tocilizumab 162 mg on D1; PK, PD and safety were assessed through D43. RESULTS: TDU13402: mean serum sarilumab exposure increased in a greater than dose proportional manner from 50 to 200 mg dose with no clinically meaningful increase in treatment-emergent adverse events (TEAEs). PDY14191: PK profiles of single-dose sarilumab 150 mg or tocilizumab 162 mg were similar; some numerical differences in PD profiles and TEAEs were observed. Neutrophil count decreased/neutropenia was the most frequently reported TEAE with sarilumab treatment in both studies. CONCLUSIONS: PK, PD and safety profiles of single-dose sarilumab SC with/without methotrexate were consistent with results anticipated in Japanese patients with RA.
35286798 Fatal multiorgan dysfunction following repeated iodinated radiocontrast injection in a pat 2022 Jun BACKGROUND: Methotrexate is an antimetabolite drug that blocks dihydrofolate reductase and impairs cellular DNA synthesis. Administration of intravenous iodinated radiocontrast agents can cause life-threatening toxicity in patients receiving methotrexate. CASE: A 60-year-old female patient with rheumatoid arthritis underwent a craniotomy and clipping of a distal anterior cerebral artery aneurysm. The patient had been on low-dose oral methotrexate for the previous 5 years, which was discontinued two days before surgery. The patient received the first intravenous contrast agent injection (iohexol) during diagnostic cerebral angiography one day prior to surgery (50 ml) and the second contrast dose on the first postoperative day (60 ml). The patient developed severe methotrexate toxicity, leading to fatal multiorgan failure and death following repeated contrast imaging with intravenous iohexol. CONCLUSIONS: Even though low-dose oral methotrexate has minor adverse effects, life-threatening toxicity can be precipitated in the presence of iodinated contrast agents.