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ID PMID Title PublicationDate abstract
30787625 Sarilumab monotherapy compared with adalimumab monotherapy for the treatment of moderately 2019 PURPOSE: Treatment outcomes and direct medical costs were examined, from a US health payer perspective, of monotherapy with sarilumab 200 mg subcutaneous (SC) every 2 weeks (Q2W) vs adalimumab 40 mg SC Q2W/QW in adult patients with moderately to severely active rheumatoid arthritis who are intolerant of, inadequate responders to, or considered inappropriate candidates for continued methotrexate treatment. PATIENTS AND METHODS: Short-term analysis was based on 24-week wholesale acquisition costs of drugs and treatment response observed in the MONARCH Phase III trial (NCT02332590) per American College of Rheumatology (ACR) 20/50 criteria and European League Against Rheumatism (EULAR) Moderate/Good Disease Activity Score 28-joint count erythrocyte sedimentation rate. Long-term analysis, which also considered drug administration and routine care costs, was conducted via a 6-month decision tree and a 1- to 10-year Markov model with microsimulation of patient profiles from the MOBILITY Phase III trial (NCT01061736). Utilities and quality-adjusted life-years (QALYs) were estimated by mapping 6-month ACR levels to a relative change in Health Assessment Questionnaire - Disability Index score and via published algorithms. RESULTS: For sarilumab and adalimumab, respectively, 24-week drug costs were $18,954 and $29,232, and costs per responder were $26,435 vs $50,055 on ACR20; $41,475 vs $98,425 on ACR50; and $22,511 vs $41,230 on EULAR Moderate/Good. Base case results at 10 years for total costs and QALYs were $176,977 and 2.75 for sarilumab and $212,136 and 2.61 for adalimumab, respectively. Sarilumab was consistently the more effective and cost-saving treatment across all short-term and long-term incremental analyses. CONCLUSION: Sarilumab monotherapy was the economically dominant treatment on incremental cost per responder and incremental cost per QALY compared with adalimumab monotherapy. These results were maintained within the sensitivity analyses.
31167161 Lung cancer combined with methotrexate-associated lymphoproliferative disorder: A case rep 2019 INTRODUCTION: Methotrexate (MTX)-associated lymphoproliferative disorder occurs in rheumatoid arthritis patients treated with MTX; however, patients with concomitant pulmonary lesions are rare. We present a case of lung cancer combined with MTX-associated lymphoproliferative disorder for which, for which it was necessary to differentiate these from possible pulmonary metastasis. PRESENTATION OF A CASE: A 72-year-old man was referred to our hospital for treatment of squamous cell carcinoma in the left upper bronchus. He was receiving oral MTX and prednisolone for rheumatoid arthritis for 15 years. However, chest computed tomography performed 1 week before surgery revealed a 1-cm-sized pulmonary nodule in the right lung. Surgical pulmonary resection of the right lung tumor revealed substantial B-cell lymphoma-type lymphoproliferative disorder. Left upper lobectomy for the squamous cell carcinoma in the left upper bronchus was performed 5 weeks after the first surgery. Chest CT performed 2 weeks after the first surgery revealed a new 1-cm-sized nodule in the lower left lung lobe. However, after discontinuing oral MTX therapy, the new lesion in the left lower lobe disappeared. DISCUSSION AND CONCLUSION: In lung cancer patients treated with MTX for rheumatoid arthritis, MTX-associated lymphoproliferative disorder should be considered as a differential diagnosis.
30697263 Prevalence and clinical characteristics of rheumatoid arthritis in Poland: a nationwide st 2019 Jan INTRODUCTION: There are no reliable data regarding the prevalence of rheumatoid arthritis (RA) in Poland. MATERIAL AND METHODS: The first stage was a face-to-face survey on a nationwide representative sample of 3000 people, which identified respondents with a physician-confirmed diagnosis of RA. The second stage was a survey of RA patients, which characterized the disease course and treatment. It was evaluated by analysis of a representative group of 1957 RA patients in routine clinical practice. RESULTS: The overall RA prevalence in Poland was 0.9% (95% CI: 0.6-1.2%), 1.06% for women, 0.74% for men. Seventy-eight percent were female, mean age was 56 and mean disease duration 7 years. Younger patients (< 50) remained professionally active in 90% of cases. Thirty percent of patients were diagnosed within 3 months of the first RA symptoms, while for 17% it took more than 1 year. Fifty-six percent of newly diagnosed patients were characterized by high disease activity (DAS-28 > 5.1). Presently, low disease activity (DAS-28 < 3.2) was found in 38.5% of patients. In Poland, 94% of patients have been treated with non-steroid anti-inflammatory drugs, almost 80% with glucocorticoids. Meanwhile, methotrexate, as an anchor drug in Poland, has been used by 80% of patients, biological agents by 2.94% of patients. CONCLUSIONS: This is the first cross-sectional population-based epidemiological study regarding prevalence of RA in the adult Polish population. The results demonstrate a high prevalence, falling within the upper boundary estimates for Europe. Despite ongoing treatment, the majority still have moderate to high disease activity, and the use of biological therapies is low.
31239736 Cost-effectiveness analysis of baricitinib versus adalimumab for the treatment of moderate 2019 Background: Baricitinib is an oral janus kinase inhibitor for the treatment of rheumatoid arthritis (RA) and is approved in Europe for use in adults with moderately-to-severely active RA and an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy. To date, no economic evaluations have assessed the cost-effectiveness of baricitinib in the Spanish setting. Objectives: To evaluate the cost-effectiveness of baricitinib versus adalimumab for the treatment of moderately-to-severely active RA in the Spanish setting. Methods: A discrete event simulation model was developed in Microsoft Excel. Costs and outcomes were estimated over a lifetime horizon using the Spanish national payer perspective. The model compared baricitinib 4 mg once daily in combination with methotrexate with adalimumab 40 mg every other week in combination with methotrexate. Effectiveness and physical function were captured using the American College of Rheumatology criteria and the Health Assessment Questionnaire-Disability Index, input values of which were derived from a phase 3, double-blind, placebo- and active-controlled trial (RA-BEAM; funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01710358). Costs are presented in Euros, 2018 values. Results: In the base case analysis, baricitinib was associated with a quality-adjusted life year gain of 0.09 years over a lifetime horizon, at an incremental cost of -€558 versus adalimumab. Results of various scenario analyses and probabilistic sensitivity analysis generally were consistent with the base case analysis. Conclusion: This analysis suggests that baricitinib is a cost-effective treatment option compared to adalimumab for Spanish patients with moderately-to-severely active RA and a previous inadequate response or intolerance to csDMARD therapy.
30858707 New alternative in the treatment of rheumatoid arthritis: clinical utility of baricitinib. 2019 Baricitinib is an innovative small-molecule drug that reversibly inhibits continuous activation of JAK/STAT pathway, thus reducing joint inflammation. The drug was approved for use as monotherapy or in combination with methotrexate (MTX) in the treatment of adults with moderately to severely active rheumatoid arthritis (RA). The aim of this paper was to review the studies on pharmacology, mode of action, pharmacokinetics, efficacy, and safety of baricitinib in patients with RA. Baricitinib provides an innovative approach to modulating the immune and inflammatory response in patients with RA, which is especially important in individuals who do not respond to disease-modifying antirheumatic drugs or standard biologic drugs (tumor necrosis factor inhibitors) or who lose response over time. Baricitinib therapy reduces symptoms of RA and improves the quality of life. Moreover, it has shown high efficacy and an acceptable safety profile in Phase III randomized controlled trials (RCTs) and become another JAK inhibitor approved for RA treatment, providing a useful alternative option. RCTs have revealed a significant benefit of baricitinib over placebo, MTX, and adalimumab in terms of standard efficacy outcomes, especially the American College of Rheumatology ACR20, ACR50, and ACR70 response rates. Additionally, a clinically meaningful improvement in patient-reported outcomes, including the quality of life, compared with placebo has been reported. The safety profile seems acceptable, although some rare but potentially severe adverse events have been observed, such as serious infections, opportunistic infections (eg, herpes zoster), malignancies, and cardiac or hepatic disorders. Baricitinib administered at an approved dose of 2 or 4 mg once daily offers a novel and promising alternative to parenterally administered biologic drugs used in RA treatment.
30970641 Host-Microbiome Synergistic Control on Sphingolipid Metabolism by Mechanotransduction in M 2019 Apr 9 Chronic inflammatory autoimmune disorders are systemic diseases with increasing incidence and still lack a cure. More recently, attention has been placed in understanding gastrointestinal (GI) dysbiosis and, although important progress has been made in this area, it is currently unclear to what extent microbiome manipulation can be used in the treatment of autoimmune disorders. Via the use of appropriate models, rheumatoid arthritis (RA), a well-known exemplar of such pathologies, can be exploited to shed light on the currently overlooked effects of existing therapies on the GI microbiome. In this direction, we here explore the crosstalk between the GI microbiome and the host immunity in model arthritis (collagen induced arthritis, CIA). By exploiting omics from samples of limited invasiveness (blood and stools), we assess the host-microbiome responses to standard therapy (methotrexate, MTX) combined with mechanical subcutaneous stimulation (MS) and to mechanical stimulation alone. When MS is involved, results reveal the sphingolipid metabolism as the trait d'union among known hallmarks of (model) RA, namely: Imbalance in the S1P-S1PR1 axis, expansion of Prevotella sp., and invariant Natural Killer T (iNKT)-penia, thus offering the base of a rationale to mechanically modulate this pathway as a therapeutic target in RA.
31700250 Safety of Intra-articular Methotrexate Injection With and Without Electroporation for Infl 2019 The general disease activity of patients with rheumatoid arthritis (RA) is well controlled by disease-modifying antirheumatic drugs, but local inflammation often remains in a few small joints. Electroporation, making small pores in cell membranes, has proven useful for drug delivery. The safety of a combination therapy of methotrexate (MTX) and electroporation for local joint inflammation in RA was investigated in a prospective, randomized, double-blind, placebo-controlled, exploratory study (UMIN000016606). The patients were randomly allocated to groups receiving a combination of MTX and electroporation (True-EP) and MTX alone (False-EP) groups. The MTX solution was injected into finger joints under ultrasound guidance. The True-EP group underwent electroporation with MTX, and the False-EP group was given MTX but only pinched using the electrode. The ultrasound grade, disease activity, and safety were evaluated from baseline to 26 weeks. Five patients (3 True-EP and 2 False-EP) with a mean age of 57.4 years and disease duration of 10.2 years were enrolled. The grey-scale grade was unchanged in 3 cases (2 True-EP and 1 False-EP) and increased in 2 cases (1 True-EP and 1 False-EP). Disease activity was alleviated in 3 cases (2 True-EP and 1 False-EP). No patients experienced burned skin or electroshock. The combination therapy of electroporation and MTX was safe for RA patients.
31909075 Nonsurgical management of temporomandibular joint autoimmune disorders. 2019 INTRODUCTION: Temporomandibular disorders (TMD) are observed in a number of autoimmune diseases but limited studies have assessed the effect of autoimmune diseases on TMD. Therefore, the present review article was conducted to determine the effect of autoimmune diseases on TMD. METHODS: International databases, including Web of Sciences, PubMed and Scopus, were searched in order to find related articles. The search key words were; temporomandibular joint (TMJ) autoimmune disorders, TMJ, TMD, medical therapy and non-invasive, local and systemic management. Published articles from June, 2010 to June, 2019 were included in the review. RESULTS: A total of 11 related articles including rheumatoid arthritis (RA), lupus erythematosus and systemic sclerosis were found. All articles noted that TMJ has unique features that distinguishes it from other human body joints. Cases of TMJ injury and TMD require specific treatments. Therefore, early diagnosis of TMD is essential. It was also mentioned in the articles that the collagen-induced arthritis (CIA) method is a suitable method for investigating TMD and its relationship with RA. Treatment methods included oral steroids, Disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, methotrexate 75 mg, and combination therapy with methotrexate. CONCLUSION: Based on the results of this study, TMD exists in some autoimmune diseases, including RA, lupus erythematosus and systemic sclerosis. Therefore, there should be an interdisciplinary collaboration between physicians and dentists in order to choose the best conservative treatment and medication therapy for TMD to reduce the progression and pain associated with this type of disorder.
31105830 MicroRNA-147 negatively regulates expression of toll-like receptor-7 in rat macrophages an 2019 Background/Introduction: Aberrant expression of Toll like receptors (TLR) plays a vital role in pathogenesis of rheumatoid arthritis (RA). Micro RNAs (miRs) could play important role in the related signaling pathways. The present study was undertaken to establish the link between miR-147 and TLR-7 in rat macrophages (in vitro) and in pristane (PS) induced arthritic rats. METHODOLOGY: Dual luciferase assay was done to confirm the interaction between miR-147 and TLR-7. The effect of miR-147 on regulation of TLR-7 was done by RT-qPCR and Immunoblotting studies in rat macrophages (ATCC(®) CRL-2192(TM)) after treating them with miR-147 mimics and inhibitors. R-848 (Imiquimod) was used as TLR-7 stimulant, the mRNA and protein expression levels of IFN-β and TNF-α were recorded to determine the regulation of TLR-7. The levels of miR-147 and TLR-7 were evaluated during induction of rat bone marrow derived macrophage in the PS induced rat macrophages and spleens of methotrexate exposed rats. The miR-147 mimics was injected intraperitoneal to the PS treated rats and the severity of arthritis was studied. RESULTS: The study confirmed TLR-7 mRNA as the potential target of miR-147 in rats. Alterations in miR-147 by transfecting mimics or inhibitors in ATCC(®) CRL-2192(TM) cells exhibited suppression and amelioration of TLR-7 and cytokine expression. The alteration in expression of miR-147 was inversely correlated with expression of TLR-7 during bone marrow derived macrophages induction in PS exposed cells and spleens. The abnormal expression was reversed in spleens of methotrexate treated arthritic rats. The treatment of miR-147 mimic caused suppression in expression of TLR-7 and improved the severity of arthritis in PS induced arthritic rats. CONCLUSIONS: MiR-147 inversely regulates the TLR-7 signaling by targeting TLR-7 itself both in vivo and in vitro. The study provides a novel approach for conditions involving abnormal TLR-7 expression in arthritis.
31548745 Tofacitinib in the treatment of active rheumatoid arthritis - single-centre experience. 2019 OBJECTIVES: To assess the efficacy and safety profile of tofacitinib taken orally at a dose of 10 mg/day in patients with severe active rheumatoid arthritis (RA). MATERIAL AND METHODS: The retrospective observational study included 10 patients (6 women and 4 men) with RA treated with tofacitinib. All the patients had high disease activity (DAS28 [ESR] > 5.1), despite therapy with two synthetic disease-modifying antirheumatic drugs (DMARDs). Before the initiation of treatment, routine laboratory tests were performed, and disease activity was assessed in all the subjects. RESULTS: The mean age of the patients in the study group was 58.18 years (43-67). The average duration of RA was 9.9 years (2-24). The mean baseline value of DAS28 (ESR) was 6.37. Tofacitinib was used in combination with a conventional DMARD in all study subjects: with methotrexate in the majority of patients, and with leflunomide and an antimalarial drug in three patients. The mean duration of therapy with tofacitinib was 7.57 months (3.9-10.8). A significant decrease in the disease activity was observed (p < 0.05). A reduction in DAS28 (ESR) score was seen already after the first month of therapy, and the trend was maintained during subsequent months of follow-up. The mean value of DAS28 (ESR) after 6 months was 2.78. A slight increase in the serum concentration of HDL cholesterol was observed during treatment. In one patient symptoms of chronic upper respiratory tract infection led to discontinuation of the drug. The observed adverse events were of mild/moderate degree. CONCLUSIONS: The results of our retrospective observational study conducted in the setting of daily clinical practice confirm a good clinical response to tofacitinib. Despite the observed adverse effects, in the light of the available data tofacitinib demonstrates a favourable safety profile. JAK kinase inhibitors - a new class of drugs - will enable a wider population of patients to achieve remission or low disease activity.
33458667 Joint Surgery in Tunisian Rheumatoid Arthritis Patients: Prevalence and Risk Factors. 2020 Sep OBJECTIVES: This study aims to assess the prevalence of joint surgery in Tunisian patients with rheumatoid arthritis (RA) and to determine the risk factors of surgical treatment. PATIENTS AND METHODS: This retrospective cross-sectional study was performed over a period of 15 years between January 2000 and December 2014 and included 500 Tunisian patients with RA (78 males, 422 females; mean age 53.4 years; range, 21 to 83 years). The prevalence of joint surgery indication was evaluated. Clinical, paraclinical and therapeutic characteristics of RA were compared according to the need of surgery. RESULTS: Female to male ratio was 5. The indication of joint surgery was noted in 59 patients (12%). Knee joint surgery was the most performed surgical procedure (56% of surgical treatment). A decrease in surgery prevalence from 30% in 2004 to 4% in 2013 was noted. Statistical study showed that factors associated with joint surgery were: delayed diagnosis (p=0.037), long RA duration (p=0.017), young onset of RA (p<0.001), presence of joint deformities (p=0.034), presence of osteoporosis (p=0.029), presence of antinuclear antibodies (p<0.001), combination therapy of methotrexate with other conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (p=0.001), short period of first medical treatment (p=0.012) and high erythrocyte sedimentation rate (ESR) (p=0.027). In multivariate analysis, three factors were independently related to the use of joint surgery: age at disease onset [odds ratio (OR): 2.799 95% confidence interval (CI): 1.49-5.22; p=0.01], high ESR level (OR: 2.807 95% CI: 1.5-5.24; p=0.01) and association of methotrexate with other csDMARDs (OR: 3.500 95% CI: 1.61-7.56; p=0.01). CONCLUSION: Twelve percent of RA patients needed joint surgical treatment. Predictive factors of surgery were age at disease onset, high ESR level and association of methotrexate with other csDMARDs.
31833011 A Comparative Study to Assess the Efficacy, Safety, and Immunogenicity of YLB113 and the E 2020 Mar INTRODUCTION: YLB113 is a biosimilar of the reference product (RP), etanercept, under development for treatment of patients with moderate-to-severe rheumatoid arthritis (RA) and other approved indications. A phase 3 study was conducted in Europe, Japan, and India to compare the efficacy, safety, and immunogenicity of YLB113 with the RP over a treatment period of 52 weeks. METHODS: Overall, 528 patients with moderate-to-severe RA receiving concomitant methotrexate were randomized to receive a once-weekly, subcutaneous dose of 50 mg YLB113 or the RP. The primary endpoint was ACR20 response rate at week 24, with similarity confirmed if the 95% confidence interval (CI) for YLB113 and the RP was within the range of - 15 to 15%. Safety and immunogenicity endpoints were assessed to week 52. RESULTS: Based on the European analysis, in the full analysis set, ACR20 response at week 24 was 83.3% and 88.5% for YLB113 and the RP, respectively. Responses were within the predefined clinical equivalence margin. The sensitivity analysis in the per protocol set revealed a similar proportion of subjects exhibiting ACR20 response at week 24 between groups, with a difference of - 5.1% (95% CI - 11.07 to 0.81). The incidence of treatment-emergent adverse events was comparable between groups, and the incidence of antidrug antibody development to week 24 favored YLB113 (0.8 vs. 8.3%). CONCLUSIONS: This study demonstrated biosimilarity of YLB113 to the RP regarding efficacy, safety, and immunogenicity in patients with moderate-to-severe RA. Based on the same mechanism of action, biosimilarity could be extrapolated to other therapeutic indications approved for etanercept. TRIAL REGISTRATION: EudraCT Number: 2015-002,809-12.
31721017 Spebrutinib (CC-292) Affects Markers of B Cell Activation, Chemotaxis, and Osteoclasts in 2020 Mar INTRODUCTION: Spebrutinib (CC-292) is an orally administered, covalent, small-molecule inhibitor of Bruton's tyrosine kinase (BTK), part of the B-cell and Fc receptor signaling pathways. This study evaluated spebrutinib pharmacology and mechanism of action over a 4-week treatment period in patients with active rheumatoid arthritis (RA). METHODS: Primary human B cells, T cells, natural killer cells, macrophages, dendritic cells, basophils, and osteoclasts were treated with spebrutinib in vitro. Clinical pharmacodynamics were studied in 47 patients with active RA on background methotrexate therapy randomized to oral spebrutinib 375 mg/day or placebo. RESULTS: In vitro, spebrutinib inhibited B-cell proliferation more potently than T-cell proliferation and reduced both lymphoid and myeloid cytokine production and degranulation, as well as osteoclastogenesis. Clinical efficacy trended higher in spebrutinib-treated RA patients, with 41.7% (10/24) achieving ≥ 20% improvement in ACR response criteria (ACR20) versus 21.7% (5/23) of placebo patients at week 4 (P = 0.25). Treatment-emergent adverse events were comparable between treatment groups. In spebrutinib-treated patients, median BTK occupancy in peripheral blood was 83%, and significant increases in total CD19(+) and mature-naive CD27(-)CD38(-)IgD(+) B cells and decreases in transitional CD27(-)CD38(+) B cells were observed. Spebrutinib significantly reduced serum chemokines chemokine ligand 13 (CXCL13), macrophage inflammatory protein-1β (MIP-1β), and the bone resorption biomarker carboxy-terminal collagen cross-linking telopeptide (CTX-I) (P < 0.05). Clinical response to spebrutinib was associated with lower increases in CD19(+) B cells and greater decreases in CXCL13 and MIP-1β from baseline to week 4. High CD19(+) B cells and low CTX-I at baseline were associated with better spebrutinib clinical response. CONCLUSIONS: Spebrutinib inhibited various leukocyte responses in vitro, including those of B cells and osteoclasts. In this small study in RA patients, spebrutinib was well tolerated, showed a downward trend for symptoms, significantly modulated B-cell populations, and reduced markers of chemotaxis and osteoclast activity. TRIAL REGISTRATION: NCT01975610.
31908843 Correction: Abatacept in combination with methotrexate in Japanese biologic-naive patients 2019 [This corrects the article DOI: 10.1136/rmdopen-2018-000813.].
30989021 Au Clusters Treat Rheumatoid Arthritis with Uniquely Reversing Cartilage/Bone Destruction. 2019 Apr 3 Super-small nanoclusters may intrinsically trigger specific molecular pathway for disease treatment in vitro/vivo. To prove the hypothesis the super-small nanoclusters, e.g., Au clusters, are directly used to treat rheumatoid arthritis (RA) in vitro/vivo. RA is a chronic autoimmune disease that is characterized by the inflammation of joints and the unreversible destruction of the cartilage/bone. Au clusters significantly suppress lipopolysaccharide (LPS)-induced proinflammatory mediator production in the murine macrophage cell line by inhibiting the signaling pathways that regulate the major proinflammatory mediator genes. In preclinical rat RA studies, Au clusters strongly prevent type II collagen-induced rat RA without systemic side effects. Compared with the clinical first-line anchored anti-RA drug, methotrexate, Au clusters equally inhibit inflammation in vivo. Type II collagen-induced rat RA is characterized with the destruction of cartilage/bone; treatment with Au clusters reverses the destruction of cartilage/bone to its normal state. This is because Au clusters directly inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and function through the downregulation of osteoclast-specific genetic marker expression. However the methotrexate almost has no positive effect for this key issue in rat RA therapy. These data prove that the super-small nanoclusters, e.g., Au clusters, could be a novel candidate nanodrug for RA treatment.
31408659 Anti-arthritic effect of β-caryophyllene and its ameliorative role on methotrexate and/or 2019 Sep 15 AIM: Rheumatoid arthritis (RA) is the most widespread inflammatory arthropathy, which causes severe disability. It is highly important to ameliorate the side effects caused by different drugs used to treat RA. Therefore, this study assessed the potential role of β-caryophyllene (BCP) in treating adjuvant-induced arthritis (AIA), increasing the efficacy of methotrexate (MTX) and/or leflunomide (LEF), and ameliorating their side effects. MATERIAL AND METHODS: AIA was induced in rats by injecting complete Freund's adjuvant. The rats were divided into different groups such as sham group; control group; monotherapy groups, including BCP (300 mg/kg), MTX (1 mg/kg), and LEF (10 mg/kg); and combined groups, including MTX + BCP, LEF + BCP, MTX + LEF, and MTX + LEF + BCP groups. KEY FINDINGS: Monotherapy with BCP or MTX or LEF as well as MTX + LEF significantly reduced paw thickness and arthritic index; the histopathological changes in hind paw joints were recovered; and oxidative stress and tumor necrosis factor-alpha (TNF-α) levels in arthritic rats were reduced. The co-administration of BCP and MTX and/or LEF significantly improved the therapeutic efficacy of MTX and/or LEF and significantly reduced the myelosuppressive and hepatotoxic effects of MTX and/or LEF. Taken together, BCP could be used with MTX and/or LEF for the treatment of RA to reduce the side effects of the drugs and increase their efficacy.
30679916 Comparative analysis of US real-world dosing patterns and direct infusion-related costs fo 2019 PURPOSE: The objectives of this study were to evaluate and compare treatment patterns and infusion-related health care resource expenditures for rheumatoid arthritis (RA) patients initiating golimumab for intravenous use (GLM-IV) and infliximab (IFX) therapy and to assess cost implications from the commercial perspective. METHODS: Adult RA patients with a new episode of GLM-IV or IFX treatment between Janu-ary 1, 2014 and March 31, 2016 were identified from MarketScan databases and evaluated for maintenance infusion intervals and related costs of treatment. IFX and GLM-IV patients were matched 1:1 on index medication treatment duration, gender, payer type, prior biologic use, and post-index methotrexate use. Paid amounts for drugs and associated administration costs were applied to treatment group dosing patterns. RESULTS: Final matched treatment groups included 547 GLM-IV and 547 IFX patients (mean age = 55-56 years). Mean (SD) follow-up was 609 (161) days for GLM-IV and 613 (163) days for IFX. Treatment duration was 396 (240) days for GLM-IV and 397 (239) days for IFX. Overall, 80% of GLM-IV and 39% of IFX maintenance infusions were given approximately every 8 weeks; and 6% of GLM-IV and 53% of IFX maintenance infusions occurred more frequently than every 8 weeks (P<0.001). When weighting of the maintenance infusion interval was applied, the mean number of induction plus maintenance infusions during the first year of treatment was estimated at 7.03 for GLM-IV and 9.48 for IFX. From the commercial perspective, drug plus administration costs per infusion were $5,846 for GLM-IV and $5,444 for IFX with total annual cost of therapy for GLM-IV patients costing $10,507 less than that for IFX patients in the first year and $6,774 less than that for IFX patients in subsequent years. CONCLUSION: Annual GLM-IV drug plus administration costs for commercial health plans were significantly less than IFX in RA patients due to differences in real-world dosing and administration.
31853152 Observational study of inflammatory arthritis treatment by etanercept originator switched 2019 OBJECTIVES: The aim of the study was to assess the safety and efficacy of switching an etanercept originator to an etanercept biosimilar in rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis patients. MATERIAL AND METHODS: In 162 patients etanercept originator treatment had been replaced with the biosimilar (Group 1), and in six patients the biosimilar was initiated as the first biological agent (Group 2). The efficacy and safety of the treatment were monitored at 3-6 months. RESULTS: In the majority of patients in Group 1 (n = 138) the etanercept biosimilar was well tolerated, whereas in 24 patients a switch back to the originator was required. The loss of efficacy was confirmed in nine patients using clinical scoring system, and nine patients reported subjective loss of efficacy; 13 patients reported adverse events, most often headache (n = 3) and skin lesions (n = 3). In four patients injection site reactions were present. The adverse events (AE) and/or the loss of the biosimilar efficacy were more commonly observed in women, patients with rheumatoid arthritis (especially in those who did not receive methotrexate), and in patients with a previous history of any other biological treatment. In patients in Group 2 the therapy was effective and no adverse events were observed. CONCLUSIONS: The etanercept biosimilar seems to be effective and well-tolerated in the majority of patients. Nevertheless, in some cases, switching from the originator to the biosimilar was associated with AEs or loss of efficacy.
31303928 [Renal amyloidosis complicating adult onset Still's disease: about three cases]. 2019 Renal amyloidosis is a rare complication of adult onset Still's disease. We here report three cases of renal amyloidosis in a series of 33 cases of adult onset Still's disease. The three patients enrolled had an average age of 43 years (with a range from 33 to 58 years). The diagnosis of Still's disease was retained on the basis of febrile polyarthritis (3 cases) associated with fleeting rush (1 case), biologic inflammatory syndrome in the absence of any infectious, inflammatory or neoplastic causes. All patients were treated with corticosteroids secondarily associated with methotrexate due to destructive polyarthritis (2 cases) and to a recurrence (1 case). Renal amyloidosis had occurred 4.9 years after Still's disease (with a range from 33 months to 7 years). Amyloidosis was revealed by nephrotic syndrome (3 cases) associated with renal failure (1 case). Diagnosis was based on renal puncture biopsy (3 cases) which showed AA amyloidosis (2 cases) and untyped amyloidosis (1 case). All patients received colchicine. Outcome was favorable in a female patient while in the other two patients the disease progressed to chronic renal failure. Renal amyloidosis uncommonly results from adult onset Still's disease. Once the disease gets established it can be life-threatening.
32743513 Programmed death ligand 2 - A link between inflammation and bone loss in rheumatoid arthri 2020 OBJECTIVE: Active rheumatoid arthritis (RA) is accompanied by increased appendicular and axial bone loss, closely associated to the degree of inflammation. The programmed death-1 (PD-1) pathway is important for maintaining peripheral tolerance, and its ligand PD-L2 has recently been associated with bone morphogenetic protein activity. Here, we report that PD-L2 plays a central role in RA osteoimmunology. METHODS: Femoral bone mineral density (BMD) and trabecular bone microstructure were evaluated by micro-CT in wild type (WT) and PD-L2(-/-) mice. Osteoclasts were generated from RA synovial fluid mononuclear cells and peripheral blood monocytes. The effects of recombinant PD-L2, was evaluated by tartrate-resistant acid phosphatase (TRAP) activity and the development of bone erosions in the presence of anti-citrullinated protein antibodies (ACPA). Plasma soluble (s)PD-L2 levels were measured in patients with early (e)RA (n ​= ​103) treated with methotrexate alone or in combination with the TNF inhibitor Adalimumab. RESULTS: PD-L2(-/-) mice had a decreased BMD and deteriorated trabecular bone microstructure that was not related to the RANKL/OPG pathway. PD-L2 decreased TRAP activity in osteoclasts and decreased ACPA-induced erosions. In the RA synovial membrane PD-L2 was highly expressed especially in the lining layer and plasma sPD-L2 levels were increased in eRA patients and decreased with treatment. One-year sPD-L2 correlated inversely with erosive progression two years after treatment initiation with methotrexate and placebo. CONCLUSION: PD-L2 regulates bone homeostasis in RA. Our findings provide new insight into the relationship between the immune system and bone homeostasis, and suggest a potential therapeutic target for limiting inflammatory bone loss in RA.