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ID PMID Title PublicationDate abstract
32376462 Sialic acid-modified chitosan oligosaccharide-based biphasic calcium phosphate promote syn 2020 Jul 10 Therapeutic goals for rheumatoid arthritis (RA) consist of inhibiting the inflammatory response and repairing the damaged bone/cartilage. Tissue engineering could achieve both goals, however, it was hindered due to the lack of biologically relevant tissue complexity, limitation in covering the entire polyarthritis lesions and requirement of extra surgical implantation. Integrating nanotechnologies into clinically sized implants represents a major opportunity to overcome these problems. Herein, we designed a sialic acid (SA)-modified chitosan oligosaccharide-based biphasic calcium phosphate (BCP), a biomimetic nanoplatform that could load with methotrexate. We found that SA modification could not only improve the accumulation of the designed organic-inorganic nanoplatform in arthritic paws (34.38% higher than those without SA modification at 48 h), but also cooperate with BCP to exert synergetic mineralization of calcium phosphate, allowing more osteoblasts to attach, proliferate and differentiate. The more differentiated osteoblasts produced 4.46-fold type I collagen and 2.60-fold osteoprotegerin compared to the control group. Besides, the disassembled nanorods released chitosan oligosaccharide-based micelles, revealing a cartilage-protective effect by reducing the loss of glycosaminoglycan. All these improvements contributed to the light inflammatory response and reduced destruction on cartilage/bone. The findings provide a novel strategy for RA therapy via nanometer-scale dimension mimicking the natural tissues.
32147565 Important determinants of the patient choice between TNF- vs. non-TNF Biologic disease-mod 2020 Jul OBJECTIVE: To assess why patients choose TNF- versus non-TNF biologics for treating active rheumatoid arthritis (RA) after methotrexate-failure. METHODS: Participants responded to the question "What sort of things help a patient decide the treatment choice between the two types of injectable biologics, TNF biologic versus non-TNF biologic, for treating active rheumatoid arthritis when methotrexate fails to control RA disease activity?" They nominated responses, discussed and then voted. RESULTS: Forty-four patients participated in 10 nominal groups (Birmingham; n=6; New York City: n=4), who were predominantly female (86%), 68% white, with a mean age of 65 (standard deviation [SD], 12) years. Present/past DMARDs included methotrexate in 91%, glucocorticoids in 11%, and biologics and/or Jak-inhibitors in 68% of participants. Pain and fatigue were mild-moderate with means of 3.9 (SD, 2.5) and 4.3 (SD, 2.5), respectively, on 0-10 scale; mean morning joint stiffness was 1.3hours (SD, 2.1). The number of groups that nominated each response and total votes were as follows: (1) Side effects/fear of side effects: 10/10; 31% votes (82/264); (2) Efficacy/ability to reduce joint damage: 9/10; 30% votes (80/264); (3) Doctor's opinion, 6/10; 12% votes (32/264); (4) Cost, 7/10; 9% votes (25/264); (5) Other drugs/comorbidity, 4/10; 12% votes (31/264); (6) Experience of others/information-seeking/own research, 2/10; 2% votes (5/264); (7) Newness, 1/10; 2% votes (6/264); and (8) Convenience/frequency of use, 1/10; 1% votes (3/264). CONCLUSIONS: We identified the patient perspective of choice between TNF versus non-TNF biologic for treating active RA. This knowledge can help in informative shared decision-making in clinical care.
32892311 Managing rheumatoid arthritis during COVID-19. 2020 Nov The outbreak of coronavirus in the world has led to an uncertainty about treatment of patients with autoimmune disorders because of their weakened immune system coupled with immunosuppressive agents they take which predisposes them to a host of infections. Data on COVID-19 patients with underlying rheumatological diseases has been emerging mostly in the form of small case series and one global registry. From these data, it seems like our patients, although immunosuppressed, are not particularly susceptible to the coronavirus infection and if infected, do not have significantly worse outcomes than other patients. In fact, drugs like hydroxychloroquine, dexamethasone, and tocilizumab have been studied for treatment of COVID-19. However, this is only preliminary data, and since a few parts of the world are still grappling with the pandemic at its peak, we need to be equipped on how to protect and manage our immunosuppressed patients. Published evidence to guide treatment decisions are lacking and doubts regarding continuation and initiation of immunosuppressants remain. Rheumatoid arthritis (RA) is the most common immune-mediated disorder in COVID-19 patients, and in this review, we discuss how the commonly used drugs in RA alter the patients' susceptibility to this infection. The review also summarizes the recommendations from the major bodies on how to manage this disease in these times. Key Points • Patients on immunosuppressive medications are not found to be at a greatly increased risk of acquiring COVID-19 infection. • Patients doing well on a stable dose of steroid and/or Disease-Modifying Antirheumatic Drugs (DMARDs) should be allowed to continue the same unless they get infected in which case, temporary stoppage of methotrexate and leflunomide may be considered. • Initiation of high-dose steroids, DMARDs, and biologics, if the clinical situation demands so, can be done. • Maintenance biologic therapy for stable patients should be individualized by the treating physician.
32078955 PRP-chitosan thermoresponsive hydrogel combined with black phosphorus nanosheets as inject 2020 May Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease causing destruction of bone and cartilago articularis. Traditional treatment methods have many side effects, or too concerne about the anti-inflammatory mechanisms but ignore osteanagenesis. In this work, a novel therapeutic platform combined black phosphorus nanosheets (BPNs) into platelet-rich plasma (PRP)-chitosan thermoresponsive hydrogel has been prepared for management of RA. The BPNs generate local heat upon near-infrared irradiation, and delivering reactive oxygen species (ROS) to the inflamed joints simultaneously for removing hyperplastic synovial tissue. The injectable chitosan thermoresponsive hydrogel can take control of the releasing of BPNs degradation products, which provide ample raw materials for osteanagenesis. In addition, the PRP can effectively improve the adhesion and increase capacity of mesenchymal stem cells on chitosan thermosensitive hydrogels. And this thermoresponsive hydrogel can protect articular cartilage by reducing the friction on the surrounding tissue. Drug delayed release property was indicated by the release and uptake of methotrexate. The edema degree of the arthritic mouse was reduced obviously by the BPNs/Chitosan/PRP thermoresponsive hydrogel. Both in vitro and in vivo studies suggest that the thermoresponsive hydrogel can provide a potential possibility for the management of RA.
31761888 Nivolumab for Methotrexate-associated Classic Hodgkin's Lymphoma in a Rheumatoid Arthritis 2020 Mar 15 Nivolumab exerts therapeutic activity in patients with classic Hodgkin's lymphoma (CHL) but may cause several types of immune-related adverse events. Some rheumatoid arthritis (RA) patients develop CHL during methotrexate therapy (MTX-CHL); however, the efficacy and safety of nivolumab for these patients remain unclear. A 68-year-old woman was diagnosed with CHL after six years of MTX therapy for RA. The disease did not respond to any type of chemotherapy. Nivolumab was then initiated, and the patient was successfully treated without the reactivation of RA. The reactivation of RA always needs to be considered with the administration of nivolumab.
33025946 Peficitinib hydrobromide to treat rheumatoid arthritis. 2020 Aug Peficitinib hydrobromide is a small Janus kinase inhibitor (JAK1, JAK2, JAK3 and TYK2) molecule for the treatment of rheumatoid arthritis (RA). Phase II and phase III clinical trials and extension studies with different doses have been conducted to assess the drug's efficacy and safety with substantially improved outcomes observed in RA. This JAK inhibitor oral drug demonstrated clinical response as once-daily monotherapy in patients with moderate to severe RA, also in combination with methotrexate (MTX), who had an inadequate response to MTX. The findings from studies of this new JAK inhibitor have shown that, both in monotherapy as well as in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), it has efficacy, safety and tolerability in RA patients.
33001390 Rituximab as a treatment option in a patient with rheumatoid arthritis and a history of ma 2021 Feb When compared to general population, patients with rheumatoid arthritis are at higher risk of some malignancies (especially lymphomas and lung cancer). Genetic predisposition, chronic inflammatory stimuli and viral infections are some of the reasons untreated patients are at higher risk. Clinical studies and national/international registries collect the data about the malignancies with higher incidence (such as lung, skin and breast cancer) but on the other hand, malignancies with lower incidence (such as sarcomas) are rarely reported. We report a case of a 47-year-old male with a history of a malignant intracranial chondrosarcoma/osteochondroma who developed seropositive rheumatoid arthritis. Due to progression of erosions, the patient was initialy treated with conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) and later on with rituximab. The patient's rheumatoid arthritis went and remained in remission on maintenance therapy with rituximab (every 6-8 months) and low-dose methotrexate with no relapse of malignant intracranial chondrosarcoma/osteochondroma. Rituximab should be considered as a treatment option in patients with rare and agressive malignancies, such as sarcomas.
33346891 Efficacy and safety of iguratimod combined with methotrexate vs. methotrexate alone in rhe 2021 Jun The current systematic review and meta-analysis aims to evaluate the efficacy and safety of iguratimod (IGU) combined with methotrexate (MTX) versus MTX alone in rheumatoid arthritis (RA). Two independent investigators searched for original randomized controlled trials (RCTs) related to the combination of IGU and MTX in RA published before November 1, 2019, in PubMed, Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), and WanFang Data. Additionally, we searched clinical trial registry websites. We assessed the methodological quality of the included trials using the Cochrane Collaboration tool and the seven-point Jadad scale. Statistical analyses were performed using Review Manager (RevMan) 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Meta-regression and publication bias analyses were performed using Stata version 14 software (StataCorp., College Station, TX, USA). A total of 7 RCTs consisting of 665 participants, with 368 participants in the active arm and 297 in the placebo arm, were included in the meta-analysis. The American College of Rheumatology (ACR) value was better in the IGU + MTX group than in the MTX alone group, with a pooled relative risk (RR) for ACR20 (American College of Rheumatology 20% improvement criteria), ACR50, and ACR70 of 1.40 (95% CI, 1.13-1.74), 2.09 (95% CI, 1.67-2.61), and 2.24 (95% CI, 1.53-3.28), respectively. The results of the meta-analysis demonstrated that there was no statistical significance in adverse events (1.06 (95% CI, 0.92-1.23)). The combined treatment is an effective, safe, and economical treatment option for patients who do not respond well to methotrexate alone or for patients who cannot afford expensive biologics that have no confirmed efficacy.
33243729 [Mechanism of Xiaowugui decoction for treating collagen-induced arthritis in mice]. 2020 Nov 30 OBJECTIVE: To explore the mechanism of Xiaowugui decoction (XWGD) decoction in treating rheumatoid arthritis (RA) in mice. METHODS: Healthy male DBA/1 mice were used for CIA modeling. Twenty-five CIA mice with successful modeling and similar arthritis index (AI) scores were randomized equally into model group (CIA), methotrexate (MTX) group, and low-, medium-, and high-dose XWGD groups (0.975, 1.95, and 3.9 g/mL, respectively), with another 5 normal mice as the normal control group. The mice in normal control and CIA groups were given saline once a day, those in MTX group were given 0.1 mg/mL MTX once a week, and those in XWGD groups were treated daily via garage of XWGD containing crude drugs of different doses for 28 consecutive days. The AI score and HE staining were used to evaluate the changes in the joints of the CIA mice. The effect of XWGD on Th1, Th17, MDSC, G-MDSC and M-MDSC cells were evaluated with flow cytometry. RESULTS: Treatment with MTX and different doses of XWGD significantly decreased the AI score of the mice and relieved joint inflammation as compared with the model group (P < 0.05), and a higher dose of XWGD decoction produced a stronger therapeutic effect. Compared with those in CIA model group, the mice in MTX and XWGD treatment groups showed significantly decreased percentages of Th1, Th17 and M-MDSC cells in the spleen and increased percentages of G-MDSC cells (P < 0.01), and these changes were more conspicuous with a higher dose of XWGD. Correlation analysis showed that Th1 and Th17 cells were positively correlated with M-MDSC and negatively correlated with G-MDSC cells (P < 0.01). CONCLUSIONS: XWGD can improve joint inflammation in CIA mice by increasing the percentages of G-MDSC cells and decreasing the percentages of M-MDSC, Th1 and Th17 cells, and a high dose of XWGD can produce an equivalent therapeutic effect to methotrexate but with better safety.
32863415 Methotrexate-Induced Pancytopenia and Mucositis Caused by Medication Error. 2020 Mar The use of methotrexate in routine clinical practice is becoming more common among specialties such as rheumatology, dermatology, oncology and obstetrics. General clinicians are increasingly encountering patients on this drug. Though it has a high safety profile, there is a recognised risk of acute toxicity or long-term complications associated with its use, which can be worsened by several factors such as advanced age, moderate to severe renal impairment, low folate level and/or inadequate folate supplementation, hypoalbuminaemia, polypharmacy causing drug-drug interactions and wrongful administration. We present a case of a 45-year old woman with rheumatoid arthritis who presented with acute pancytopaenia and mucositis due to methotrexate toxicity. We highlight its peculiar dosing regimen to minimise prescribing errors. FUNDING: None.
32237478 [Meta-analysis of RCT studies on clinical efficacy of single administration of Tripterygiu 2020 Feb To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.
32345367 Tapering of biological antirheumatic drugs in rheumatoid arthritis patients is achievable 2020 Apr 28 BACKGROUND/PURPOSE: Studies have demonstrated that rheumatoid arthritis (RA) patients who achieve low disease activity or remission are able to taper biological disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to evaluate the proportion of patients in whom bDMARDs can be tapered in daily practice and to analyse the characteristics of these patients. Other objectives were to analyse which bDMARDs are more suitable for dose reduction and the cost savings. RESULTS: Data from 332 eligible RA patients from our Brussels UCLouvain cohort were retrospectively analysed; 140 patients (42.1%) received a tapered regimen, and 192 received stable doses of bDMARDs. The age at diagnosis (43.1 vs 38.7 years, p = 0.04), health assessment questionnaire (HAQ) score (1.3 vs 1.5, p = 0.048), RF positivity rate (83.3 vs 72.9%, p = 0.04) and disease duration at the time of bDMARD introduction (9.7 vs 12.1 years, p = 0.034) were significantly different between the reduced-dose and stable-dose groups. Interestingly, relatively more patients receiving a tapered dose were treated with a combination of bDMARDs and methotrexate (MTX) (86.7% vs 73.8%, p = 0.005). In our cohort, anti-TNF agents were the most commonly prescribed medications (68%). Only 15 patients experienced a flare during follow-up. Adalimumab, etanercept and rituximab were the most common bDMARDs in the reduced-dose group and were associated with the most important reductions in annual cost. CONCLUSION: In daily practice, tapering bDMARDs in RA patients who have achieved low disease activity or remission is an achievable goal in a large proportion of patients, thereby reducing potential side effects and annual drug-associated costs. The combination of bDMARDs with MTX could improve the success of dose reduction attempts. TRIAL REGISTRATION: This retrospective non-interventional study was retrospectively registered with local ethics approval.
32371431 Comparative effectiveness of improvement in pain and physical function for baricitinib ver 2020 Apr OBJECTIVE: To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised, methotrexate (MTX)-controlled trials in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)/biologic (bDMARD)-naïve RA patients using matching-adjusted indirect comparisons (MAICs). METHODS: Data were from Phase III trials on patients receiving monotherapy baricitinib, tocilizumab, adalimumab, tofacitinib or MTX. Pain was assessed using a visual analogue scale (0-100 mm) and physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI). An MAIC based on treatment-arm matching, an MAIC with study-level matching and Bucher's method without matching compared change in outcomes between therapies. Matching variables included age, gender, baseline disease activity and baseline value of outcome measure. RESULTS: With all methods, greater improvements were observed in pain and HAQ-DI at 6 months for baricitinib compared with adalimumab and tocilizumab (p<0.05). Differences in treatment effects (TEs) favouring baricitinib for pain VAS for treatment-arm matching, study-level matching and Bucher's method, respectively, were -12, -12 and -12 for baricitinib versus adalimumab and -7, -7 and -9 for baricitinib versus tocilizumab; the difference in TEs for HAQ-DI was -0.28, -0.28 and -0.30 for adalimumab and -0.23, -0.23 and -0.26 for tocilizumab. For baricitinib versus tofacitinib, no statistically significant differences for pain improvement were observed except with one of the three methods (Bucher method) and none for HAQ-DI. CONCLUSIONS: Results suggest greater pain reduction and improved physical function for baricitinib monotherapy compared with tocilizumab and adalimumab monotherapy. No statistically significant differences in pain reduction and improved physical function were observed between baricitinib and tofacitinib with the MAIC analyses.
32711562 Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a 2020 Jul 25 OBJECTIVES: Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA). METHODS: HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA). RESULTS: Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect. CONCLUSION: The novel HDAC6 inhibitor CKD-506 suppresses inflammatory responses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA.
32202079 Nanomedicines for the delivery of glucocorticoids and nucleic acids as potential alternati 2020 Sep Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects 0.5-1% of the world population. Current treatments include on one hand non-steroidal anti-inflammatory drugs and glucocorticoids (GCs) for treating pain and on the other hand disease-modifying anti-rheumatic drugs such as methotrexate, Janus kinase inhibitors or biologics such as antibodies targeting mainly cytokine expression. More recently, nucleic acids such as siRNA, miRNA, or anti-miRNA have shown strong potentialities for the treatment of RA. This review discusses the way nanomedicines can target GCs and nucleic acids to inflammatory sites, increase drug penetration within inflammatory cells, achieve better subcellular distribution and finally protect drugs against degradation. For GCs such a targeting effect would allow the treatment to be more effective at lower doses and to reduce the administration frequency as well as to induce much fewer side-effects. In the case of nucleic acids, particularly siRNA, knocking down proteins involved in RA, could importantly be facilitated using nanomedicines. Finally, the combination of both siRNA and GCs in the same carrier allowed for the same cell to target both the GCs receptor as well as any other signaling pathway involved in RA. Nanomedicines appear to be very promising for the delivery of conventional and novel drugs in RA therapeutics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.
32522251 Efficacy and safety of sarilumab in combination with csDMARDs or as monotherapy in subpopu 2020 Jun 10 BACKGROUND: The interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors. This analysis investigated the efficacy and safety of sarilumab in patient subgroups. METHODS: Data were included from phase III studies: two placebo-controlled studies of subcutaneous sarilumab 150/200 mg every 2 weeks (q2w) either + MTX in MTX-IR patients (52 weeks) or + csDMARDs in TNF-IR/INT patients (24 weeks), and a monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w in MTX-IR/INT patients (24 weeks). Prespecified and post hoc subgroups included patient demographics, disease characteristics, and prior treatments. Prespecified and post hoc endpoints included clinical, radiographic, and physical function measures, and p values are considered nominal. Safety was assessed during double-blind treatment. RESULTS: The superiority of sarilumab (either as monotherapy vs. adalimumab or in combination with csDMARDs vs. placebo + csDMARDs) across clinical endpoints was generally consistent across subgroups defined by patient demographics, disease characteristics, and prior treatments, demonstrating the benefit of sarilumab treatment for a wide range of patient types. Interaction p values of < 0.05 were consistently observed across studies only for baseline anti-cyclic citrullinated peptide antibody (ACPA) status for American College of Rheumatology 20% response, but not American College of Rheumatology 50% or 70% response. Adverse events and worsening laboratory parameters occurred more frequently in sarilumab-treated vs. placebo-treated patients and were more frequent in the small number of patients ≥ 65 years (n = 289) vs. patients < 65 years (n = 1819). Serious infections occurred in six patients aged ≥ 65 years receiving sarilumab, although the incidence of serious infections was generally higher in patients aged ≥ 65 years regardless of treatment. CONCLUSIONS: Apart from ACPA status, there were no consistent signals indicating differential effects of sarilumab in any of the subpopulations assessed. Sarilumab demonstrated consistent efficacy and safety across a wide range of patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01061736, registered on February 03, 2010; ClinicalTrials.gov NCT01709578, registered on October 18, 2012; ClinicalTrials.gov NCT02332590, registered on January 07, 2015.
32735145 Radiographic and clinical effects of 10 mg and 25 mg twice-weekly etanercept over 52 w 2021 Mar OBJECTIVES: To compare the radiographic and clinical effects of 25 versus 10 mg twice-weekly (BIW) etanercept over 52 weeks in Japanese patients with active rheumatoid arthritis (RA). METHODS: This was a post-hoc analysis of a Phase 3 study where Japanese patients with active RA were randomized to receive BIW etanercept 25 mg (n = 182), etanercept 10 mg (n = 192), or methotrexate (n = 176) for 52 weeks (NCT00445770). This analysis included assessments of week-24 and week-52 disease activity, week-52 radiographic progression, and the relationship between baseline characteristics and week 52 clinical outcomes with clinically relevant radiographic progression (CRRP) at week 52. RESULTS: At week 52, there were no significant differences between 25 and 10 mg etanercept in terms of achieving low disease activity or remission. CRRP was observed in 36% and 32% of patients in the 10 and 25 mg groups, respectively. Predictor analysis suggested that worse background disease status, treatment with methotrexate rather than etanercept, and poorer clinical outcomes at week 52 were associated with CRRP. CONCLUSIONS: The 25 mg BIW etanercept dosage does not appear to be significantly more efficacious than 10 mg in Japanese patients with RA. Further studies evaluating the optimal etanercept dosing regimen in this patient population may be merited. NCT: NCT00445770.
33060309 Benefits of Methotrexate Use on Cardiovascular Disease Risk Among Rheumatoid Arthritis Pat 2021 Jun OBJECTIVE: Methotrexate (MTX) has been associated with reduced risk for cardiovascular disease (CVD) events among patients with rheumatoid arthritis (RA) not exposed to biologic disease-modifying antirheumatic drugs (bDMARDs). The effect of concomitant MTX on CVD risk among RA patients initiating bDMARDs remains unknown. METHODS: A retrospective cohort study was conducted to assess the effect of MTX on CVD risk using 2006-2015 Medicare claims data for patients with RA initiating bDMARD. The main exposure was current use of MTX, updated in a time-varying fashion. The primary outcome was a composite of incident myocardial infarction (MI), stroke, and fatal CVD. Secondary outcomes were each event that comprised the primary outcome. Incidence rates (IR) and 95% CI were calculated using Poisson regression. Associations between MTX and risk of CVD were assessed using Cox regression. RESULTS: A total of 88,255 bDMARD initiations and 1861 CVD events were included in this study. Mean age was 64.6 (12.3) years, 84.0% were female, and 68.2% were non-Hispanic White. The crude IRs (95% CI) for CVD were 17.9 (16.9-18.8) and 12.1 (11.1-13.2) per 1000 patient-years among MTX unexposed and exposed, respectively. The multivariable adjusted HR (95% CI) for CVD events associated with MTX was 0.76 (0.68-0.85). Multivariable adjusted HRs were 0.78 (0.66-0.91), 0.74 (0.62-0.88), 0.77 (0.68-0.86), and 0.82 (0.73-0.93) for MI, stroke, MI or stroke, and a composite CVD outcome, respectively. Results were robust in sensitivity and subgroup analyses. CONCLUSION: Among patients with RA receiving biologics, concomitant MTX use was associated with a 24% lower risk for CVD events.
32532307 Predicting the treatment response of certolizumab for individual adult patients with rheum 2020 Jun 12 BACKGROUND: A model that can predict treatment response for a patient with specific baseline characteristics would help decision-making in personalized medicine. The aim of the study is to develop such a model in the treatment of rheumatoid arthritis (RA) patients who receive certolizumab (CTZ) plus methotrexate (MTX) therapy, using individual participant data meta-analysis (IPD-MA). METHODS: We will search Cochrane CENTRAL, PubMed, and Scopus as well as clinical trial registries, drug regulatory agency reports, and the pharmaceutical company websites from their inception onwards to obtain randomized controlled trials (RCTs) investigating CTZ plus MTX compared with MTX alone in treating RA. We will request the individual-level data of these trials from an independent platform (http://vivli.org). The primary outcome is efficacy defined as achieving either remission (based on ACR-EULAR Boolean or index-based remission definition) or low disease activity (based on either of the validated composite disease activity measures). The secondary outcomes include ACR50 (50% improvement based on ACR core set variables) and adverse events. We will use a two-stage approach to develop the prediction model. First, we will construct a risk model for the outcomes via logistic regression to estimate the baseline risk scores. We will include baseline demographic, clinical, and biochemical features as covariates for this model. Next, we will develop a meta-regression model for treatment effects, in which the stage 1 risk score will be used both as a prognostic factor and as an effect modifier. We will calculate the probability of having the outcome for a new patient based on the model, which will allow estimation of the absolute and relative treatment effect. We will use R for our analyses, except for the second stage which will be performed in a Bayesian setting using R2Jags. DISCUSSION: This is a study protocol for developing a model to predict treatment response for RA patients receiving CTZ plus MTX in comparison with MTX alone, using a two-stage approach based on IPD-MA. The study will use a new modeling approach, which aims at retaining the statistical power. The model may help clinicians individualize treatment for particular patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number pending (ID#157595).
31207152 Live Zoster Vaccine in Patients With Rheumatoid Arthritis Treated With Tofacitinib With or 2020 Mar OBJECTIVE: To explore herpes zoster (HZ) rates and live zoster vaccine (LZV) safety in a subset of patients with rheumatoid arthritis who received LZV before tofacitinib ± methotrexate (MTX), or adalimumab (ADA) plus MTX in the ORAL Strategy. METHODS: ORAL Strategy was a 1-year, phase IIIb/IV, randomized, triple-dummy, active-comparator-controlled study. MTX-inadequate responder patients received tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID plus MTX, or ADA 40 mg every other week plus MTX (1:1:1 randomization). Eligible patients age ≥50 years could opt to receive LZV 28 days before initiating study treatment. HZ incidence rates (IRs; patients with events per 100 patient-years) were calculated. Opportunistic HZ infections (multidermatomal/disseminated), serious HZ events, and LZV-related adverse events were monitored. RESULTS: In ORAL Strategy, 216 of 1,146 patients (18.8%) received LZV. Overall, 18 patients (1.6%) developed HZ (vaccinated: n = 3; nonvaccinated: n = 15). HZ IRs were 1.1 (95% confidence interval [95% CI] 0.3-2.9), 2.3 (95% CI 1.0-4.6), and 1.7 (95% CI 0.6-3.7) for tofacitinib monotherapy, tofacitinib plus MTX, and ADA plus MTX, respectively, and were generally similar between vaccinated and nonvaccinated patients. Three multidermatomal, 1 disseminated, and 2 serious HZ events occurred. No vaccinated patients had zoster-like lesions within 42 days of vaccination; 1 patient had vaccination-site erythema. CONCLUSION: LZV was well tolerated, and HZ IRs were generally similar between treatment groups and vaccinated versus nonvaccinated patients. However, ORAL Strategy was not powered for comparisons between vaccinated and nonvaccinated patients because <20% of all patients were vaccinated. Furthermore, LZV has been shown to be effective only in ~50% of individuals.