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1.
Clin Rheumatol ; 43(6): 2133-2138, 2024 Jun.
Article En | MEDLINE | ID: mdl-38703283

INTRODUCTION: Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce. METHODS: From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years. RESULTS: In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups. CONCLUSION: In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points • Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages • An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed • No significant differences in infection incidence were found between tofacitinib and baricitinib.


Antirheumatic Agents , Arthritis, Rheumatoid , Azetidines , Janus Kinase Inhibitors , Piperidines , Purines , Pyrazoles , Pyrimidines , Sulfonamides , Humans , Male , Janus Kinase Inhibitors/therapeutic use , Janus Kinase Inhibitors/adverse effects , Female , Middle Aged , Arthritis, Rheumatoid/drug therapy , Purines/therapeutic use , Purines/adverse effects , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Piperidines/therapeutic use , Piperidines/adverse effects , Aged , Pyrimidines/therapeutic use , Pyrimidines/adverse effects , Sulfonamides/therapeutic use , Sulfonamides/adverse effects , Azetidines/therapeutic use , Azetidines/adverse effects , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Incidence , Herpes Zoster/epidemiology , Herpes Zoster/chemically induced , Adult , Infections/epidemiology , Infections/chemically induced
2.
BMJ Case Rep ; 17(5)2024 May 31.
Article En | MEDLINE | ID: mdl-38821562

We present a case of a woman in her 30s who visited the rheumatology clinic due to her persistent knee pain for 5 years, which spread to multiple joints. She was diagnosed with seropositive rheumatoid arthritis (RA). While most joints responded well to methotrexate and subsequently etanercept, persistent unilateral knee pain prompted further investigation. Imaging revealed synovitis and joint effusion in her knee, prompting arthroscopy and synovial biopsy, revealing pigmented villonodular synovitis (PVNS). Despite initial success with a tricompartmental synovectomy, her disease recurred. The decision was made to pursue medical therapy, with pexidartinib initiated by the oncology team. Our case report highlights the importance of considering other underlying conditions in patients with RA who do not achieve full clinical improvement despite standard treatment. Physicians should remain vigilant for atypical presentations and imaging features in patients with RA, for early recognition of PVNS can significantly impact treatment decisions and patient outcomes.


Arthritis, Rheumatoid , Knee Joint , Synovitis, Pigmented Villonodular , Humans , Synovitis, Pigmented Villonodular/diagnosis , Female , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/diagnosis , Knee Joint/pathology , Knee Joint/diagnostic imaging , Adult , Arthroscopy , Arthralgia/etiology , Synovectomy , Antirheumatic Agents/therapeutic use , Magnetic Resonance Imaging , Diagnosis, Differential
3.
Int Immunopharmacol ; 134: 112167, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38754279

BACKGROUND: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage. METHODS: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method. RESULTS: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias. CONCLUSIONS: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.


Spondylarthritis , Tumor Necrosis Factor Inhibitors , Humans , Spondylarthritis/drug therapy , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Symptom Flare Up , Drug Tapering , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/administration & dosage , Randomized Controlled Trials as Topic
5.
RMD Open ; 10(2)2024 May 20.
Article En | MEDLINE | ID: mdl-38772677

OBJECTIVES: Non-adherence to rheumatoid arthritis (RA) treatments must be identified. A methotrexate (MTX) urinary dosage (METU) was recently developed. The aim of our study was to assess adherence to MTX in RA using METU in real-life conditions and to compare it with indirect adherence measurement technics. METHODS: We performed a cross-sectional study at Reims University Hospital. We included over 18-year-old patients with RA treated by MTX for more than 6 months. Patients were invited to complete demographic, clinical and psychological questionnaires and adherence measurement technics (Compliance Questionnaire of Rheumatology (CQR) and Medication Possession Ratio (MPR)). A urinary sample was collected to measure MTX and information about tolerance was evaluated through Methotrexate Intolerance Severity Score. RESULTS: 84 patients were included, 26 using oral MTX, 58 subcutaneous (SC) MTX. Among them, 73% were female, mean age was 61.5 years, MTX mean dose was 15 mg/week and 61.9% were treated by biological DMARDs (Disease Modifying Antirheumatic Drugs). 77 patients (91.7%) were adherent to treatment according to METU, whereas MPR and CQR reported less adherence (69.5% and 61.9%, respectively). MPR and METU were not significantly different in SC MTX users (p=0.059). Non-adherent patients had a higher number of tender joints and C reactive protein value (p<0.05). CONCLUSION: This is the first largest study evaluating MTX adherence in patients with RA using a urinary dosage. We identified that indirect adherence measurements did not reflect real-life adherence. It would be appreciable to realise METU, in a new study, in patients with RA with unexplained response to treatment, to consider it before escalating therapeutic strategy.


Antirheumatic Agents , Arthritis, Rheumatoid , Medication Adherence , Methotrexate , Humans , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/urine , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Methotrexate/adverse effects , Female , Male , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/administration & dosage , Cross-Sectional Studies , Middle Aged , Aged , Surveys and Questionnaires , Adult , Biomarkers/urine
7.
Int J Rheum Dis ; 27(5): e15189, 2024 May.
Article En | MEDLINE | ID: mdl-38769844

BACKGROUND: To describe the 3- and 5-year outcomes of an inception cohort of Australian children with JIA for whom 1-year outcomes have previously been published. METHODS: Data regarding clinical outcomes of the original cohort of 134 patients at 3 and 5 years were sought. Relevant clinical features and medication exposures entered prospectively into an electronic record were collected and analyzed using descriptive statistics. RESULTS: Data were available for 110 and 98 patients at 3 and 5 years, respectively. The proportion of patients with active joints progressively decreased from 34% at 12 months to 21% at 3 years and 16% at 5 years. Cumulative exposure to methotrexate increased between 3 and 5 years (75%-80%), however, point prevalence use decreased (45%-41%). Cumulative exposure and point prevalence use of bDMARDS both increased between 3 and 5 years; 30%-42% and 29%-33%, respectively. Thirty-five percent of patients had inactive joint disease off medications at 5 years, which occurred most frequently in patients with sJIA and oligoarthritis. CONCLUSION: Five-year outcomes of Australian children with JIA are good, with only a small minority having ongoing active joint disease at 5 years. bDMARDS play an increasing role in management over time; however, methotrexate use remains significant. A majority of children remain on medications at 5 years.


Antirheumatic Agents , Arthritis, Juvenile , Methotrexate , Humans , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/epidemiology , Arthritis, Juvenile/diagnosis , Male , Female , Child, Preschool , Treatment Outcome , Child , Methotrexate/therapeutic use , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Time Factors , Australia/epidemiology , Remission Induction , Prospective Studies , Adolescent , Disease Progression
8.
Int J Rheum Dis ; 27(5): e15196, 2024 May.
Article En | MEDLINE | ID: mdl-38769886

INTRODUCTION: Systemic juvenile idiopathic arthritis (sJIA) is a distinct disease subset, with a poorer prognosis compared with other JIA subsets. Tocilizumab has an important role in the management of sJIA refractory to standard initial therapy. However, no specific guidelines exist for the tapering of tocilizumab therapy in sJIA, which could have implications on the overall cost and side effects of treatment. METHODS: This was an observational study which included 21 children with refractory sJIA, who were initially put on injection tocilizumab every 2 weekly, with subsequent dosing tapered to 4 weekly and 6 weekly intervals based on JIA ACR 70 responses at 12 and 24 weeks, respectively. The primary outcome at week 36 included JIA ACR 30, 50, 70, and 90 response rates with other efficacy and safety measures as secondary outcomes. RESULTS: At 36 weeks, JIA ACR 30, 50, 70, and 90 responses were observed in 90.5%, 90.5%, 71.4%, and 52.4% patients respectively along with significant improvement in hematological and inflammatory parameters. The mean prednisolone dose could be reduced from 0.54 to 0.13 mg/kg/day and around 29% patients were able to discontinue steroids altogether. No serious adverse events were recorded. With drug tapering, we could curtail on 26% of the total tocilizumab dose that would have been otherwise required on the continuous 2 weekly protocol. CONCLUSIONS: Tocilizumab, used in an early response-based tapering regimen, was both safe and efficacious in children with sJIA refractory to standard therapy. Larger and longer duration studies are required to further validate our observations.


Antibodies, Monoclonal, Humanized , Antirheumatic Agents , Arthritis, Juvenile , Drug Tapering , Humans , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/diagnosis , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Female , Child , Male , Treatment Outcome , Time Factors , Child, Preschool , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Adolescent , Prednisolone/administration & dosage , Prednisolone/adverse effects , Remission Induction , Drug Administration Schedule
9.
Tidsskr Nor Laegeforen ; 144(6)2024 May 14.
Article En, Nor | MEDLINE | ID: mdl-38747669

Background: A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review. Case presentation: The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level. Interpretation: Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.


Medication Errors , Methotrexate , Humans , Female , Methotrexate/adverse effects , Methotrexate/administration & dosage , Aged , Dyspnea/chemically induced , Leucovorin/adverse effects , Leucovorin/administration & dosage , Antidotes/administration & dosage , Antidotes/therapeutic use , Antirheumatic Agents/adverse effects , Antirheumatic Agents/administration & dosage
10.
Front Immunol ; 15: 1359041, 2024.
Article En | MEDLINE | ID: mdl-38711497

Background: Immunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients. Methods: Fifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment. Results: Compared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients. Conclusion: Exogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.


Antibodies, Monoclonal, Humanized , Arthritis, Rheumatoid , Drug Therapy, Combination , Interleukin-2 , Adult , Aged , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Interleukin-2/administration & dosage , Interleukin-2/adverse effects , Interleukin-2/therapeutic use , Treatment Outcome
12.
J Manag Care Spec Pharm ; 30(5): 480-489, 2024 May.
Article En | MEDLINE | ID: mdl-38701025

BACKGROUND: Rituximab (RTX) is an anti-CD20 monoclonal antibody that is used to treat various conditions in cancer, rheumatoid arthritis (RA), and multiple sclerosis (MS). Although RTX has been used in the United States for almost 3 decades, questions remain regarding its real-world utilization and effectiveness. OBJECTIVE: To describe the state of observational research and real-world evidence evaluating RTX in oncology, RA, and off-label use in MS. METHODS: A broad search was conducted in MEDLINE, Embase, and CINAHL covering the period of January 2010 to June 2022. Two reviewers independently screened all identified records for each disease category (cancer, RA, MS) beginning with title review, followed by abstract, and full-text review to identify relevant publications to include in the final analysis. Data were extracted and summarized for each disease based on overall trends, similarities, and differences across included studies and stratified by disease state. RESULTS: A total of 260 studies met eligibility criteria, with 79 studies for the RA cohort, 144 for cancer, and 37 for MS. Across all disease cohorts, most studies (n = 189; 72.7%) were retrospective. 171 (65.8%) studies used hospital or electronic health record data as their data source and 65 (23.2%) used registry databases. Most studies (n = 153; 58.8%) assessed the effectiveness of RTX measured by disease-specific endpoints, followed by safety (n = 60; 23.1%), treatment patterns (n = 32; 12.3%), and descriptive analyses assessing treatment adherence and economic burden of disease (n = 16; 6.2%). Although safety was not the primary outcome for most studies, the majority of studies across all disease states still reported some form of safety measure. Conclusive statements on RTX's benefit varied across disease states, with MS having the most (n = 30; 81.1%) studies suggesting the drug's positive benefit. There were limited studies assessing RTX use, associated economic burden, and biosimilar switching. CONCLUSIONS: The findings underscore the need for health care providers to better understand the treatment landscape and utilization of RTX, particularly in terms of patient selection, timing of initiation, and long-term outcomes. Real-world evidence can help support health care decisions and treatment using rituximab.


Arthritis, Rheumatoid , Multiple Sclerosis , Neoplasms , Rituximab , Humans , Multiple Sclerosis/drug therapy , Rituximab/therapeutic use , Arthritis, Rheumatoid/drug therapy , Neoplasms/drug therapy , Antirheumatic Agents/therapeutic use , Treatment Outcome , Observational Studies as Topic , Off-Label Use
13.
Pediatr Rheumatol Online J ; 22(1): 53, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730442

BACKGROUND: Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial. METHODS: 92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week. RESULTS: 32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4-10), median 10 months (7-16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6-9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group. CONCLUSIONS: Escalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety. TRIAL REGISTRATION: Dutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585 .


Antirheumatic Agents , Arthritis, Juvenile , Drug Therapy, Combination , Etanercept , Methotrexate , Humans , Arthritis, Juvenile/drug therapy , Etanercept/administration & dosage , Etanercept/therapeutic use , Etanercept/adverse effects , Female , Male , Child , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/therapeutic use , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Child, Preschool , Dose-Response Relationship, Drug , Treatment Outcome , Prednisolone/administration & dosage , Sulfasalazine/administration & dosage , Sulfasalazine/therapeutic use
14.
PLoS One ; 19(5): e0302308, 2024.
Article En | MEDLINE | ID: mdl-38709812

Rheumatoid arthritis causes joint inflammation due to immune abnormalities, resulting in joint pain and swelling. In recent years, there have been considerable advancements in the treatment of this disease. However, only approximately 60% of patients achieve remission. Patients with multifactorial diseases shift between states from day to day. Patients may remain in a good or poor state with few or no transitions, or they may switch between states frequently. The visualization of time-dependent state transitions, based on the evaluation axis of stable/unstable states, may provide useful information for achieving rheumatoid arthritis treatment goals. Energy landscape analysis can be used to quantitatively determine the stability/instability of each state in terms of energy. Time-series clustering is another method used to classify transitions into different groups to identify potential patterns within a time-series dataset. The objective of this study was to utilize energy landscape analysis and time-series clustering to evaluate multidimensional time-series data in terms of multistability. We profiled each patient's state transitions during treatment using energy landscape analysis and time-series clustering. Energy landscape analysis divided state transitions into two patterns: "good stability leading to remission" and "poor stability leading to treatment dead-end." The number of patients whose disease status improved increased markedly until approximately 6 months after treatment initiation and then plateaued after 1 year. Time-series clustering grouped patients into three clusters: "toward good stability," "toward poor stability," and "unstable." Patients in the "unstable" cluster are considered to have clinical courses that are difficult to predict; therefore, these patients should be treated with more care. Early disease detection and treatment initiation are important. The evaluation of state multistability enables us to understand a patient's current state in the context of overall state transitions related to rheumatoid arthritis drug treatment and to predict future state transitions.


Antirheumatic Agents , Arthritis, Rheumatoid , Arthritis, Rheumatoid/drug therapy , Humans , Cluster Analysis , Antirheumatic Agents/therapeutic use , Female , Middle Aged , Male , Cohort Studies , Aged , Adult , Time Factors
15.
PLoS One ; 19(5): e0298679, 2024.
Article En | MEDLINE | ID: mdl-38696444

INTRODUCTION: Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. METHODS: We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. RESULTS: Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. CONCLUSION: In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.


Antirheumatic Agents , Arthritis, Juvenile , Recurrence , Humans , Arthritis, Juvenile/drug therapy , Adult , Male , Female , Young Adult , Adolescent , Retrospective Studies , Antirheumatic Agents/therapeutic use , Risk Factors , Proportional Hazards Models
17.
Front Immunol ; 15: 1400097, 2024.
Article En | MEDLINE | ID: mdl-38799449

This report describes the case of a 48-year-old woman who presented with sternoclavicular joint arthritis after administration of an immune checkpoint inhibitor (ICI), durvalumab, for small cell lung carcinoma. The onset of arthritis transpired 18 months after the commencement of the ICI therapeutic regimen and demonstrated resilience to glucocorticoid treatment. After excluding infectious aetiologies and metastatic involvement, the patient was diagnosed with ICI-induced arthritis (ICI-IA). Considering the articular implications akin to the SAPHO syndrome, the patient was treated with infliximab, resulting in complete resolution. This finding implies that biological DMARDs can serve as effective interventions for ICI-induced sternoclavicular joint arthritis. Given the heterogeneous nature of its pathogenesis, the selection of therapeutic agents may require customization based on the distinct clinical presentation of each individual case.


Arthritis , Immune Checkpoint Inhibitors , Infliximab , Sternoclavicular Joint , Humans , Female , Infliximab/therapeutic use , Infliximab/adverse effects , Middle Aged , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Arthritis/drug therapy , Arthritis/chemically induced , Arthritis/etiology , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/immunology , Treatment Outcome , Antibodies, Monoclonal
18.
Arch Dermatol Res ; 316(5): 194, 2024 May 22.
Article En | MEDLINE | ID: mdl-38775951

Hydroxychloroquine (HCQ) is an immunomodulator used in dermatology and rheumatology. Side effects may be observed on routine monitoring studies before they become clinically apparent. The goal of this retrospective chart review was to assess laboratory abnormalities in dermatologic and rheumatologic patients taking HCQ. Medical records of patients prescribed HCQ were retrospectively reviewed. Demographics, reported side effects, and parameters on baseline and follow-up complete blood count (CBC) and comprehensive metabolic panel (CMP) were recorded and graded. Laboratory abnormalities were considered severe if they were grade 3 or greater according to Common Terminology Criteria for Adverse Events v3.0 and persistent if they continued beyond subsequent laboratory testing. Of 646 eligible charts, 289 had monitoring studies for review. There were 35 severe (grade 3 or 4, 35/289; 12%) adverse events that developed, as noted on CBC or CMP. Of these 35 severe adverse events, 25 self-corrected on subsequent testing, and 10 (10/289, 3%) across 9 patients were persistent, including glomerular filtration rate, alanine transferase, alkaline phosphatase, glucose, hemoglobin and lymphopenia abnormalities. Of these 10 abnormalities, 7/10 (70%) were unlikely due to hydroxychloroquine use according to the calculated Naranjo score for each patient. Severe laboratory abnormalities while taking hydroxychloroquine are rare, even in a population with a high rate of comorbidities. Among the abnormalities observed, the majority of them (70%) were likely due to disease progression or a medication other than hydroxychloroquine. CBC and CMP monitoring for the reason of observing abnormalities while on HCQ should be at the discretion of the prescribing physician.


Drug Monitoring , Hydroxychloroquine , Humans , Hydroxychloroquine/adverse effects , Female , Middle Aged , Retrospective Studies , Male , Adult , Aged , Drug Monitoring/methods , Antirheumatic Agents/adverse effects , Rheumatic Diseases/drug therapy , Skin Diseases/diagnosis , Skin Diseases/chemically induced , Skin Diseases/drug therapy
19.
Medicine (Baltimore) ; 103(18): e38002, 2024 May 03.
Article En | MEDLINE | ID: mdl-38701278

BACKGROUND: The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis. METHODS: Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value. RESULTS: We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously. CONCLUSIONS: Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.


Antirheumatic Agents , Arthritis, Juvenile , Network Meta-Analysis , Arthritis, Juvenile/drug therapy , Humans , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Antirheumatic Agents/administration & dosage , Randomized Controlled Trials as Topic , Treatment Outcome , Adalimumab/therapeutic use , Adalimumab/adverse effects , Adalimumab/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin 1 Receptor Antagonist Protein/adverse effects , Bayes Theorem
20.
Int Immunopharmacol ; 134: 112239, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38761785

We aimed to identify an expression profile of lncRNAs potentially related to treatment response in Psoriatic arthritis (PsA) patients, to be used as potential genomic biomarkers predictors of drug treatment effectiveness. In addition, we evaluated a possible association between lncRNAs genetic variants and the response to therapy using the clinical parameter of Disease Activity Index. For the expression study, we collected 48 treated PsA patients, monitoring the treatment response for 12 months. We initially used PCR Array and, then, we validated the results with qRT-PCR. We also retrospectively genotyped 163 treated PsA patients. Firstly, we observed a significant difference in the expression level between Responder and non-Responder patients, of 4 lncRNAs in the group of PsA patients treated with TNFi and of 3 lncRNAs in the group of patients treated with IL17i. Then, we confirmed a significant decrease of MEG3 expression in non-Responder patients compared to Responders, also considering separately the single groups of patients treated with TNFi and IL17i. In addition, our results seem to highlight a potential dose-dependent effect of rs941576 (MEG3) variant allele on Disease Activity Index. Our study suggests a possible role of the lncRNA MEG3 in the treatment response to biological drugs.


Arthritis, Psoriatic , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/genetics , Male , Female , Middle Aged , Adult , Treatment Outcome , Retrospective Studies , Biomarkers , Polymorphism, Single Nucleotide , Interleukin-17/genetics , Interleukin-17/metabolism , Biological Products/therapeutic use , Antirheumatic Agents/therapeutic use
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