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Current Opinion in Rheumatology Sep 2023Disease-modifying antirheumatic drugs (DMARDs) have dramatically improved patient outcomes in juvenile idiopathic arthritis (JIA). However, these medications may also... (Review)
Review
PURPOSE OF REVIEW
Disease-modifying antirheumatic drugs (DMARDs) have dramatically improved patient outcomes in juvenile idiopathic arthritis (JIA). However, these medications may also result in physical, psychologic, and economic burden, which must be balanced with risk of flare off treatment. Although some children remain in remission after medication discontinuation, evidence is sparse for if, when, and how medications should be de-escalated once achieving clinically inactive disease (CID). We review the data on medication discontinuation and the role of serologic and imaging biomarkers in JIA.
RECENT FINDINGS
The literature uniformly supports early biologic DMARD initiation, although the optimal timing and strategy for medication withdrawal in patients with sustained CID remains unclear. In this review, we present the current data on flare frequency and time to flare, clinical factors associated with flare, and recapture data for each JIA category. We also summarize the current knowledge on the role of imaging and serologic biomarkers in guiding these treatment decisions.
SUMMARY
JIA is a heterogenous disease for which prospective clinical trials are needed to address the question of when, how, and in whom to withdraw medication. Research investigating the roles of serologic and imaging biomarkers may help improve the ability to ascertain which children can successfully de-escalate medications.
Topics: Child; Humans; Arthritis, Juvenile; Prospective Studies; Antirheumatic Agents; Remission Induction; Biomarkers; Treatment Outcome
PubMed: 37139831
DOI: 10.1097/BOR.0000000000000948 -
Frontiers in Immunology 2023Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to... (Review)
Review
Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren 's syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod's unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Chromones; Sjogren's Syndrome; Cytokines
PubMed: 37809072
DOI: 10.3389/fimmu.2023.1150661 -
Clinical Rheumatology Oct 2023Rheumatoid arthritis (RA) increases the risk of cardiovascular disease (CVD), with inflammation playing a key role. Biologic and targeted synthetic drugs used to treat... (Review)
Review
BACKGROUND
Rheumatoid arthritis (RA) increases the risk of cardiovascular disease (CVD), with inflammation playing a key role. Biologic and targeted synthetic drugs used to treat RA can induce systemic immunomodulation and may have pleiotropic effects on vascular function, making it crucial to investigate their impact on CVD risk in RA patients.
METHODS
A systematic review of the literature was conducted to investigate the impact of biologic and targeted synthetic treatments approved for RA on various cardiovascular markers, including endothelial function, arterial stiffness, and subclinical atherosclerosis. Our analysis included a search of the MedLine (via PubMed) and Web of Science databases using a pre-determined search strategy. We conducted a narrative synthesis of the included studies due to heterogeneity in study design and outcome measures.
RESULTS
From an initial pool of 647 records, we excluded 327 studies based on their titles and abstracts, and we selected 182 studies for final examination. Ultimately, 58 articles met our inclusion criteria and were included in our systematic review. Our analysis of these studies revealed a positive effect of biologic and targeted synthetic therapies on vascular dysfunction associated with RA. However, the impact of these treatments on subclinical atherosclerosis was inconsistent.
CONCLUSION
Overall, our systematic review provides important insights into the potential cardiovascular benefits of biologic and targeted synthetic treatments for RA by a still unknown mechanism. These findings can inform clinical practice and contribute to our understanding of their possible effects on early vascular pathology. Key Points • Great heterogeneity of methods are used to evaluate the endothelial function and arterial stiffness in patients with RA on biologic and targeted synthetic antirheumatic drugs. • Most studies have shown a considerable improvement in endothelial function and arterial stiffness with TNFi, despite some studies reporting only transient or no improvement. • Anakinra and tocilizumab may have a beneficial effect on vascular function and endothelial injury, as indicated by increased FMD, coronary flow reserve, and reduced levels of biomarkers of endothelial function, while the overall impact of JAKi and rituximab remains inconclusive based on the reviewed studies. • To fully comprehend the distinctions between biologic therapies, more long-term, well-designed clinical trials are necessary using a homogeneous methodology.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Rituximab; Biological Products; Cardiovascular Diseases
PubMed: 36991244
DOI: 10.1007/s10067-023-06587-8 -
Arthritis Research & Therapy Jul 2023To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea. (Comparative Study)
Comparative Study
BACKGROUND
To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea.
METHODS
Using 2009-2019 Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users.
RESULTS
We included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00-2.80) for HZ, 1.04 (0.71-1.52) for SBI, and 0.25 (0.09-0.73) for OI.
CONCLUSIONS
This population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Cohort Studies; Herpes Zoster; Herpesvirus 3, Human; Janus Kinase Inhibitors; Opportunistic Infections; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 37495973
DOI: 10.1186/s13075-023-03111-w -
Advances in Therapy Dec 2023In the INBUILD trial in patients with progressive pulmonary fibrosis other than idiopathic pulmonary fibrosis (IPF), nintedanib slowed the rate of decline in forced...
INTRODUCTION
In the INBUILD trial in patients with progressive pulmonary fibrosis other than idiopathic pulmonary fibrosis (IPF), nintedanib slowed the rate of decline in forced vital capacity (FVC; mL/year) over 52 weeks compared with placebo. We assessed the efficacy of nintedanib across subgroups in the INBUILD trial by baseline characteristics.
METHODS
We assessed the rate of decline in FVC over 52 weeks and time to progression of interstitial lung disease (ILD) (absolute decline from baseline in FVC % predicted > 10%) or death over the whole trial in subgroups based on sex, age, race, body mass index (BMI), time since diagnosis of ILD, FVC % predicted, diffusing capacity of the lungs for carbon monoxide (DLco) % predicted, composite physiologic index (CPI), GAP (gender, age, lung physiology) stage, use of anti-acid therapy and use of disease-modifying antirheumatic drugs (DMARDs) at baseline.
RESULTS
The effect of nintedanib versus placebo on reducing the rate of decline in FVC over 52 weeks was consistent across the subgroups by baseline characteristics analysed. Interaction p values did not indicate heterogeneity in the treatment effect between these subgroups (p > 0.05). Over the whole trial (median follow-up time ∼19 months), progression of ILD or death occurred in similar or lower proportions of patients treated with nintedanib than placebo across the subgroups analysed, with no heterogeneity detected between the subgroups.
CONCLUSIONS
In the INBUILD trial, no heterogeneity was detected in the effect of nintedanib on reducing the rate of ILD progression across subgroups based on demographics, ILD severity or use of anti-acid therapy or DMARDs. These data support the use of nintedanib as a treatment for progressive pulmonary fibrosis.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov Identifier: NCT02999178.
Topics: Humans; Lung; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Vital Capacity; Treatment Outcome; Antirheumatic Agents; Disease Progression
PubMed: 37751022
DOI: 10.1007/s12325-023-02668-x -
Survey of Ophthalmology 2024Noninfectious uveitis (NIU) in children and adolescents is a rare but treatable cause of visual impairment in children. Treatments for pediatric NIU and their side... (Review)
Review
Noninfectious uveitis (NIU) in children and adolescents is a rare but treatable cause of visual impairment in children. Treatments for pediatric NIU and their side effects, along with the risks of vision loss and the need for long-term disease monitoring, pose significant challenges for young patients and their families. Treatment includes local and systemic approaches and this review will focus on systemic therapies that encompass corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and biological disease-modifying antirheumatic drugs (bDMARD). Treatment is generally planned in a stepwise approach. Methotrexate is well-established as the preferential csDMARD in pediatric NIU. Adalimumab, an antitumor necrosis factor (TNF) agent, is the only bDMARD formally approved for pediatric NIU and has a good safety and efficacy profile. Biosimilars are gaining increasing visibility in the treatment of pediatric NIU. Other bDMARD with some evidence in literature for the treatment of pediatric NIU include infliximab, tocilizumab, abatacept, rituximab and, more recently, Janus kinase inhibitors. Important aspects of managing children on these systemic therapies include vaccination issues, risk of infection, and psychological distress. Also, strategies need to address regarding primary nonresponse/secondary loss of response to anti-TNF treatment, biological switching, and monitoring regimens for these drugs. Optimal management of pediatric uveitis involves a multidisciplinary team, including specialist pediatric uveitis and rheumatology nurses, pediatric rheumatologists, psychological support, orthoptic and optometry support, and play specialists.
Topics: Humans; Child; Adolescent; Biosimilar Pharmaceuticals; Tumor Necrosis Factor Inhibitors; Antirheumatic Agents; Uveitis; Adrenal Cortex Hormones
PubMed: 36682467
DOI: 10.1016/j.survophthal.2023.01.002 -
Arthritis & Rheumatology (Hoboken, N.J.) Dec 2023Preliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA); however, prior studies have been small... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Preliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA); however, prior studies have been small and/or uncontrolled; this study aimed to address that gap.
METHODS
This randomized, double-blind, sham-controlled trial enrolled patients aged 18 to 75 years with active RA who had failed conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and were naïve to biologic and/or targeted synthetic DMARDs. All patients received an auricular vagus nerve stimulator and were randomized 1:1 to active stimulation or sham. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Secondary endpoints included mean changes in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI).
RESULTS
A total of 113 patients (mean age 54 years; 82% female) enrolled, and 101 patients (89.4%) completed week 12. ACR20 response at week 12 was 25.0% for active stimulation versus 26.9% for sham (difference vs. sham, -1.9; 95% CI, -18.8, 14.9, P = 0.823). The least square mean ± SE change in DAS28-CRP was -0.95 ± 0.16 for active stimulation and -0.66 ± 0.16 for sham (P = 0.201); in HAQ-DI it was -0.19 ± 0.06 for active stimulation and -0.02 ± 0.06 for sham (P = 0.044). Adverse events occurred in 17 patients (15%); all were mild or moderate.
CONCLUSION
Auricular VNS did not meaningfully improve RA disease activity. If VNS with other modalities is pursued in the future for the treatment of RA, larger, controlled studies will be needed to understand its utility.
Topics: Female; Humans; Male; Middle Aged; Antirheumatic Agents; Arthritis, Rheumatoid; C-Reactive Protein; Double-Blind Method; Treatment Outcome; Vagus Nerve Stimulation; Adolescent; Young Adult; Adult; Aged
PubMed: 37390360
DOI: 10.1002/art.42637 -
Innere Medizin (Heidelberg, Germany) Feb 2024Giant cell arteritis (GCA) and Takayasu arteritis (TAK), as the main representatives of large vessel vasculitis, are rheumatological autoimmune disorders associated with... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) and Takayasu arteritis (TAK), as the main representatives of large vessel vasculitis, are rheumatological autoimmune disorders associated with inflammatory vessel wall changes in the arterial system that can lead to many types of organ damage.
MATERIAL AND METHODS
In this review the current scientific evidence on the diagnostics and treatment of large vessel vasculitis is evaluated and discussed.
RESULTS
In addition to the medical history and clinical presentation, imaging techniques nowadays represent the core of large vessel vasculitis diagnostics and have largely replaced the histological confirmation of GCA. After the diagnosis, acute treatment with glucocorticoids should be initiated as rapidly as possible but in the long term this should be tapered out or replaced by a steroid-sparing basic treatment. In contrast to GCA with already available options and other biologic disease-modifying antirheumatic drugs (DMARDs) about to be approved, there are still no approved biologic DMARD treatment options available for the less common TAK.
CONCLUSION
In contrast to the substantial progress in imaging diagnostics of large vessel vasculitis and with respect to the treatment of GCA, the much rarer TAK still requires intensive research efforts, especially to improve the treatment situation.
Topics: Humans; Giant Cell Arteritis; Takayasu Arteritis; Glucocorticoids; Antirheumatic Agents; Biological Products
PubMed: 38240814
DOI: 10.1007/s00108-023-01656-1 -
PloS One 2023Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective treatment for RA, the effects that bDMARDs have on integumentary, cardiac, and immune systems and the high costs associated with these treatments, make that mesenchymal stem cell-based therapies (MSCs) for RA are being considered potential treatment methods. This work analyses the performance in safety and efficacy terms of MSCs techniques.
METHODS AND FINDING
A literature search was performed in PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey databases from inception to October 28, 2022. Three randomized controlled trials (RCTs) and one non-randomized controlled trial (non-RCTs), including 358 patients met our inclusion criteria and were included in qualitative synthesis; only RCTs were eligible for quantitative synthesis (meta-analysis). Meta-analysis of adverse events (AE) in RCTs showed no significant differences in the incidence of AE in the MSCs group compared to the control group (Risk ratio: 2.35; 95% CI, 0.58 to 9.58; I2 = 58.80%). The pooled Risk ratio for non-serious and serious adverse events showed no statistical difference between intervention and control groups concerning the incidence of non-serious and serious adverse events (Risk ratio: 2.35; 95% CI, 0.58 to 9.51; I2 = 58.62%) and (Risk ratio: 1.10; 95% CI, 0.15 to 7.97; I2 = 0.0%) respectively. The Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS28) decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed; however, this improvement was not shown in the studies after 12 months of follow-up without continuous treatment administration.
CONCLUSION
This Systematic review and meta-analysis showed a favorable safety profile, without life-threatening events in subjects with RA, and a trend toward clinical efficacy that must be confirmed through high-quality RCTs, considerable sample size, and extended follow-up in subjects with RA.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Methotrexate; Treatment Outcome; Controlled Clinical Trials as Topic
PubMed: 37498842
DOI: 10.1371/journal.pone.0284828 -
Clinical Rheumatology Dec 2023Comparisons of Janus kinase inhibitors (JAKi) for treatment of rheumatoid arthritis in patients with inadequate response to biologic disease-modifying anti-rheumatic...
Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib.
INTRODUCTION
Comparisons of Janus kinase inhibitors (JAKi) for treatment of rheumatoid arthritis in patients with inadequate response to biologic disease-modifying anti-rheumatic drugs are lacking. We assessed the relative efficacy and safety of four JAKi (tofacitinib, baricitinib, upadacitinib, and filgotinib) in this context.
METHOD
We performed an adjusted indirect comparison (IC) of randomized clinical trials using Bucher's method with an IC and mixed calculator. Endpoints were Disease Activity Score C-reactive protein (DAS28-CRP) and American College of Rheumatology-20 (ACR20). Equivalence was assessed using the equivalent therapeutic alternatives (ETA) guidelines.
RESULTS
We included four of 133 potentially relevant studies. IC showed no statistically significant differences between the four JAKi regarding DAS28-CRP < 3.2. Results were similar in terms of ACR20 except for tofacitinib showing lower efficacy than upadacitinib (RAR -18.4% [IC95% -33.4 to -3.5], p=0.0157). Statistically significant differences were related to the relevant difference for tofacitinib in both endpoints. Despite no statistical differences for baricitinib, we observed a probably clinically relevant difference regarding DAS28-CRP. Probably clinically relevant differences were found for tofacitinib vs. upadacitinib in both endpoints, and for baricitinib vs. upadacitinib in DAS28-CRP. Safety, drug-drug interactions, and convenience considerations did not modify the result of therapeutic equivalence assessment based on efficacy data.
CONCLUSIONS
In conclusion, our results show that filgotinib and upadacitinib are ETA. Baricitinib and upadacitinib are also ETA due to a lack of clear differences and for showing superiority over placebo. The results for tofacitinib and upadacitinib show some inconsistency and more data are needed. Key Points • To date, neither a head-to-head comparison nor an indirect comparison between the Janus kinase inhibitors has been performed in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying anti-rheumatic drugs. • We performed an adjusted indirect comparison that included randomized clinical trials of tofacitinib, baricitinib, upadacitinib, and filgotinib to assess their equivalence in this scenario. • Our results show that baricitinib and filgotinib are equivalent therapeutic alternatives compared to upadacitinib. However, there is some inconsistency in the results of tofacitinib in front of upadacitinib.
Topics: Humans; Janus Kinase Inhibitors; Methotrexate; Arthritis, Rheumatoid; Antirheumatic Agents; C-Reactive Protein; Biological Products
PubMed: 37831336
DOI: 10.1007/s10067-023-06787-2