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ID PMID Title PublicationDate abstract
33166704 [Methotrexate: How long between administration and conception?]. 2021 Feb In women of childbearing age, methotrexate is prescribed in many indications other than cancer, either chronically (psoriasis, rheumatoid arthritis, IBD, etc.) or occasionally (ectopic pregnancies). The time given to these patients to consider pregnancy is currently subject to great variability depending on the sources. Analysis of the available objective evidence suggests that it is not justified to unnecessarily lengthen this period, and that conceiving the menstrual cycle following stopping methotrexate is quite possible.
32076877 Correction to: Development of Methotrexate and Minocycline Loaded Nanoparticles for the Ef 2020 Feb 19 Typesetting error occurred and author corrections to the numbering of figures and captions at the proofing stage were not incorporated in the published article.
32990361 Maintenance of Sustained Low Disease Activity or Remission in Patients With Rheumatoid Art 2020 Oct OBJECTIVE: The purpose of this study was to evaluate maintenance of remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) who achieved remission/LDA with etanercept (ETN) plus a conventional synthetic disease-modifying antirheumatic drug (csDMARD) and to compare patients who discontinued csDMARD to receive ETN monotherapy (Mono) with those remaining on combination therapy (Combo). METHODS: Patients from the Corrona RA registry between October 1, 2001, and August 31, 2017, were eligible. The index date for the Mono cohort was the csDMARD discontinuation date; the index visit for the Combo cohort was estimated from time between ETN initiation and csDMARD discontinuation in the Mono cohort. The main outcome calculated was maintenance of remission/LDA. Patients were censored if they switched to or added a biologic DMARD, discontinued ETN, when a csDMARD was reintroduced (Mono), or if methotrexate increased more than 5 mg/d (Combo). Trimming was used to balance demographic and clinical characteristics between groups. Cox regression models were adjusted for the remaining differences across groups. RESULTS: We identified 182 Mono and 403 Combo patients; 120 Mono and 207 Combo patients remained after trimming. Most patients (approximately 80%) were biologic medication-naive before initiating ETN. At 24 months postindex, modeled percentages of patients remaining in remission/LDA were 75% for Mono and 86% for Combo (overall adjusted P = 0.057). More patients were censored for therapy change in Mono than in Combo groups (37% versus 5%), largely due to reintroduction of csDMARDs in the Mono group. CONCLUSION: Many patients with RA who achieved remission/LDA on combination therapy maintained remission/LDA with ETN monotherapy for 2 years after csDMARD discontinuation. ETN monotherapy may be a viable option for patients who discontinue csDMARDs after achieving LDA/remission.
32716841 Insufficiency fractures of the knee, ankle, and foot in rheumatoid arthritis: A case serie 2020 Jul OBJECTIVE: To evaluate cases of insufficiency fractures verified by magnetic resonance imaging (MRI) of the knee, ankle, and foot in patients with rheumatoid arthritis (RA) cared for in our clinic over an 8-year period, to identify possible risk factors, and to test these in a case-control study. METHODS: All patients in the rheumatology clinic with RA were registered prospectively in the database, DANBIO. All MRIs ordered from the clinic were registered and coded according to the anatomical region. We were thus able to retrieve all patients with RA and performed an MRI of the knee or ankle/foot. The patients with fractures constituted the case series, and the patients without fractures constituted the control group. RESULTS: The RA clinic population comprised 1,624 patients who underwent a total of 70 MRIs. CASE SERIES: 39 insufficiency fractures were identified in 32 patients; 93% were women, and the median age was 68 years (range 33-89 years). Half of the patients had a T score >-2.5. The case control group without fractures comprised 38 patients; 74% were women, and the median age was 62 years (range 32-84 years). In the case series, 20 patients experienced later additional episodes of insufficiency fractures in the knee, ankle, or foot. CONCLUSION: Insufficiency fractures of the knee, ankle, and foot are a significant cause of pain and long-lasting disability in RA. Recurrent fractures are common. Diagnosis is often delayed and confused with arthritic activity. Conventional radiography and DEXA scan are often normal. Older age, female gender, radiological erosions in hand/wrist, and treatment with methotrexate were all significantly associated with fractures.
31782724 Does biologic survival depend on co-prescribed methotrexate dose in established rheumatoid 2020 Jan OBJECTIVE: Several seminal studies have suggested that a combination therapy of biologics with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) improve disease outcomes in rheumatoid arthritis (RA). Hence, most guidelines reflect this practice. It has also been shown that methotrexate (MTX) at a dose of 8-10 mg/week is perhaps sufficient to achieve better outcomes in early RA. However, it is not clear whether this strategy enhances biologic retention in the patients with established RA. We present a real-world retrospective study to investigate whether csDMARD co-prescription improves biologic retention and the optimal dose to preserve such response. MATERIALS AND METHODS: All patients prescribed biologic therapy for RA at our center between 2003 and 2017 were identified through the departmental database. They were split into five groups based on a weekly MTX dose (≤7.5 mg, 10-17.5 mg, ≥20 mg), other csDMARD prescription, or biologic monotherapy. The one-way analysis of variance model for independent values was utilized to ascertain the significance of data. The Mann-Whitney two-tailed U test was employed to determine the significance of relationship between the monotherapy group and other arms. The significance level was predefined at 0.05. RESULTS: A total of 168 patients with 198 biologic events were included. The mean age was 59.4 years (range, 24-90 years). 78% were women. The mean disease duration was 155.6 months (range, 15-491). There was a statistically significant difference (p=0.03) in biologic retention among the five arms. Compared to monotherapy, the data remained significant for ≥20 mg MTX and csDMARD groups; however, the biologic retention in the other two MTX arms was not significant. There was no significant relationship among groups for DAS28 improvement (p=0.24). CONCLUSION: Our results suggest that to improve biologic retention, the MTX dose should be increased to 20 mg a week or more, and, in people with MTX intolerance, csDMARDs co-presciption can be an alternative strategy. Maintenance with a low-to-moderate MTX dose can lead to poorer retention rates.
32707665 Silicon Nanofluidic Membrane for Electrostatic Control of Drugs and Analytes Elution. 2020 Jul 19 Individualized long-term management of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal management of pathologies, such as diabetes, hypertension, rheumatoid arthritis. Several triggered systems for drug delivery have been demonstrated. However, they mostly rely on continuous external stimuli, which hinder their application for long-term treatments. In this work, we investigated a silicon nanofluidic technology that incorporates a gate electrode and examined its ability to achieve reproducible control of drug release. Silicon carbide (SiC) was used to coat the membrane surface, including nanochannels, ensuring biocompatibility and chemical inertness for long-term stability for in vivo deployment. With the application of a small voltage (≤ 3 V DC) to the buried polysilicon electrode, we showed in vitro repeatable modulation of membrane permeability of two model analytes-methotrexate and quantum dots. Methotrexate is a first-line therapeutic approach for rheumatoid arthritis; quantum dots represent multi-functional nanoparticles with broad applicability from bio-labeling to targeted drug delivery. Importantly, SiC coating demonstrated optimal properties as a gate dielectric, which rendered our membrane relevant for multiple applications beyond drug delivery, such as lab on a chip and micro total analysis systems (µTAS).
33164739 Treating rheumatoid arthritis with leflunomide monotherapy versus combination therapy with 2021 Jan OBJECTIVE: Combination therapies have been proposed as a strategy to control inflammation more effectively in patients with rheumatoid arthritis (RA). Few studies examine the combined effect of methotrexate (MTX) and leflunomide (LFN). This study evaluated the symptom control and side effects of the combination of MTX and LFN compared with LFN monotherapy. METHODS: We conducted a retrospective analysis of 113 patients with RA treated with either LFN alone (n=22) or in combination with MTX (n=91). Data on disease activity score 28 erythrocyte sedimentation rate (DAS-28 ESR), DAS-28 C-reactive protein (DAS-28 CRP), blood cell count, liver enzymes, and creatinine levels were determined. Samples were collected on day 0 (initiation of LFN) and at 6 and 12 months. RESULTS: We found no differences between the 2 groups in DAS-28 on day 0 and at 6 and 12 months (p=0.89, p=0.42, and p=0.09, respectively, for DAS-28 ESR; p=0.97, p=0.27, and p=0.63, respectively, for DAS-28 CRP). In addition, we observed no differences in the blood cell count, liver enzymes, and creatinine levels between the treatment groups at any of the time points (all p>0.05). CONCLUSION: Our results suggest that the efficacy of the combined treatment with MTX and LFN is similar to that of LFN alone. No increase in toxicity was observed with the combination therapy.
32291887 Clinical efficacy and safety of certolizumab pegol in cutaneous symptoms on psoriasis in p 2020 May We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor-alpha agent, as monotherapy on skin psoriasis (PsO) in patients affect both by psoriatic arthritis (PsA) and mild-severe PsO. To date, the CZP is authorized for the treatment of PsA, PsO beyond that rheumatoid arthritis, axial spondyloarthritis/ankylosing spondylitis, and Crohn's. Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI). Twelve patients (9M and 3F mean age 57.8 ± 8 years) were enrolled in our study. Nine patients had been previously treated with others biologic agents, three patients were naïve. Clinical and laboratory evaluations including PASI, erythrosedimentation rate, and C-reactive protein were performed at baseline (BL), at Week 12 (W12), Week 24 (W24), and Week 52 (W52) of treatment. Although the combination between methotrexate and CZP is allowed, we included, in our study, patients treated only with CZP. In such a way as to be as specific as possible, topical corticosteroids, vitamin D derivatives, retinoid creams, anthralin derivatives as well as p-UVA or UV-B have been forbidden to enrolled patients. With the same purpose, all the patients used the identical moisturizing cream two times a day. Mean PASI score decreased from 18 (BL) to 0 (W52) as follows: 18 at BL, 4 at W12, 0 at W24, and 0 at W52. Severe adverse events were not reported. Safety evaluations were performed every 3 months: liver and renal functions were monitored in all patients during the treatment, and no patient presented abnormal values. To the best of our knowledge, this is the first report that highlights the efficacy of CZP as monotherapy in psoriasis with mild to severe cutaneous involvement. Although to date the drug is authorized only for PsA, our results demonstrate that CZP is safe and effective on both cutaneous and joint components representing, therefore, an effective option in the treatment of cutaneous symptoms of PsO. Limitations of our study are presented by the relatively short observation time (W52) and by numeric small study group. Long-term data with a larger number of enrolled patients are necessary in order to confirm our preliminary observations.
32546977 Using a Discrete-Choice Experiment in a Decision Aid to Nudge Patients Towards Value-Conco 2020 PURPOSE: To evaluate, in a proof-of-concept study, a decision aid that incorporates hypothetical choices in the form of a discrete-choice experiment (DCE), to help patients with early rheumatoid arthritis (RA) understand their values and nudge them towards a value-centric decision between methotrexate and triple therapy (a combination of methotrexate, sulphasalazine and hydroxychloroquine). PATIENTS AND METHODS: In the decision aid, patients completed a series of 6 DCE choice tasks. Based on the patient's pattern of responses, we calculated his/her probability of choosing each treatment, using data from a prior DCE. Following pilot testing, we conducted a cross-sectional study to determine the agreement between the predicted and final stated preference, as a measure of value concordance. Secondary outcomes including time to completion and usability were also evaluated. RESULTS: Pilot testing was completed with 10 patients and adjustments were made. We then recruited 29 patients to complete the survey: median age 57, 55% female. The patients were all taking treatment and had well-controlled disease. The predicted treatment agreed with the final treatment chosen by the patient 21/29 times (72%), similar to the expected agreement from the mean of the predicted probabilities (68%). Triple therapy was the predicted treatment 24/29 times (83%) and chosen 20/29 (69%) times. Half of the patients (51%) agreed that completing the choice questions helped them to understand their preferences (38% neutral, 10% disagreed). The tool took an average of 15 minutes to complete, and median usability scores were 55 (system usability scale) indicating "OK" usability. CONCLUSION: Using a DCE as a value-clarification task within a decision aid is feasible, with promising potential to help nudge patients towards a value-centric decision. Usability testing suggests further modifications are needed prior to implementation, perhaps by having the DCE exercises as an "add-on" to a simpler decision aid.
31745741 Myocarditis in Adult-Onset Still's Disease: Case-Based Review. 2020 Mar Cardiac involvement in adult-onset Still's disease (AOSD) usually manifests as a pericardial disease. Myocarditis is uncommon (prevalence of 7%). However, the cardiocirculatory failure is the second cause of life-threatening AOSD. Herein, we report the case of a 38-year-old man who was diagnosed with myocarditis caused by AOSD. He was treated medically with steroids and methotrexate, and his course was favorable. A literature search in PubMed/MEDLINE and Scopus databases from 1971 to 2019 identified 47 additional cases of myocarditis and AOSD. The main features found in these reports were reviewed and are the following: (i) myocarditis is a rare complication of AOSD manifested by fever, chest pain, dyspnea, and tachycardia; (ii) cardiac biomarkers, electrocardiogram (ECG), transthroracic echocardiography (ECHO), and cardiac magnetic resonance imaging (MRI) are useful noninvasive diagnostic tools; and (iii) myocarditis is a potentially life-threatening complication of AOSD but responds positively to steroids and other immunomodulatory drugs. This review suggests that this entity should be suspected in cases of acute febrile myocarditis after ruling out other causes since a prompt treatment results in a good prognosis.
33029724 Abatacept: A Review of the Treatment of Polyarticular-Course Juvenile Idiopathic Arthritis 2020 Dec Juvenile idiopathic arthritis (JIA) encompasses several forms of chronic inflammatory arthritis of unknown etiology presenting in children < 16 years of age, with a minimum symptom duration of 6 weeks. Approximately half of affected children have polyarticular-course JIA (pJIA), a functional concept related to several clinically and genetically heterogeneous JIA categories (systemic, extended oligoarthritis, polyarticular rheumatoid factor-positive or rheumatoid factor-negative, enthesitis-related arthritis, and psoriatic arthritis), which has as its defining feature the involvement of five or more joints during the disease course. Chronic inflammation and joint damage lead to the manifestations of JIA such as pain, limitation of motion, and loss of physical function, all of which negatively impact patients' quality of life. The American College of Rheumatology recommends initial treatment with a conventional synthetic disease-modifying antirheumatic drug (csDMARD), such as methotrexate (MTX) and, in patients with pJIA who have an inadequate response or intolerance to MTX, the use of a biologic DMARD (bDMARD) such as a tumor necrosis factor inhibitor, abatacept, or tocilizumab. Abatacept selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T cell activation, and thus has a distinct mechanism of action upstream of that of other currently available bDMARD treatments for rheumatic diseases. To enable physicians to make informed treatment decisions, it is important to review available data for the existing therapeutic agents. Here, we summarize the current evidence from phase III pivotal trials of intravenous (IV) and subcutaneous (SC) abatacept and from an ongoing registry of patients with JIA treated with abatacept. In the pivotal trials for IV and SC abatacept, either with or without MTX, both formulations demonstrated clinical efficacy, with a high proportion of patients achieving stringent clinical responses, as well as improvements in patient-reported outcomes and a favorable safety profile, particularly with regard to infections.
33103025 The Association of Methotrexate, Sulfasalazine, and Hydroxychloroquine Use With Fracture i 2020 Oct This study was conducted to evaluate the extent to which disease-modifying antirheumatic medications (DMARDs) used as part of a triple therapy for the treatment of rheumatoid arthritis (RA) including methotrexate, sulfasalazine, and hydroxychloroquine are associated with fractures in postmenopausal women with RA. Incident fractures following use of methotrexate, sulfasalazine, and/or hydroxychloroquine in postmenopausal women with RA in the Women's Health Initiative were estimated by Cox proportional hazards using hazard ratios (HRs) and 95% CIs after consideration of potential confounders. There were 1201 women with RA enrolled in the Women's Health Initiative included in these analyses, of which 74% were white, 17% were black, and 9% were of other or unknown race/ethnicity. Of the women with RA, 421 (35%) had not used methotrexate, sulfasalazine, or hydroxychloroquine, whereas 519 (43%) women had used methotrexate, 83 (7%) sulfasalazine, and 363 (30%) hydroxychloroquine alone or in combination at some time during study follow-up. Over a median length of 6.46 years of follow-up, in multivariable adjusted models, no statistically significant association was found between methotrexate (HR, 1.1; 95% CI, 0.8-1.6), sulfasalazine (HR, 0.6; 95% CI, 0.2-1.5), or hydroxychloroquine (HR, 1.0; 95% CI, 0.7-1.5) use and incident fractures or between combination therapy with methotrexate and sulfasalazine or methotrexate and hydroxychloroquine use (HR, 0.9; 95% CI, 0.5-1.6) and incident fractures. In conclusion, postmenopausal women with RA receiving any component of triple therapy should not be expected to have any substantial reduction in fracture risk from use of these DMARDs. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
33304673 Hypogonadotropic Hypogonadism and Juvenile Idiopathic Arthritis in an African Boy: What is 2020 Nov 5 The association between hypogonadotropic hypogonadism and juvenile chronic arthritis has rarely been reported in the literature. We report an untreated case of systemic juvenile idiopathic arthritis in a young African male with co-presentation of hypogonadotropic hypogonadism. Possible pathophysiological and etiological links are discussed. A 16-year-old boy was received in our outpatient department for chronic arthritis with temporomandibular involvement and fever. There was no family history of rheumatic diseases or psoriasis. Body temperature was 39.5°C at admission. The clinical examination found synovitis of wrists and knees and inflammatory lymphadenopathy. This polyarthritis occurred in a context of hypogonadism marked by impuberism of Tanner classification stage P2G2. Laboratory tests showed biological inflammatory syndrome and hyperferritinemia with collapsed glycosylated ferritin at 11%. Hormonal testing found low blood testosterone (0.08 mg/L) and pituitary hormone levels attesting to hypogonadotropic hypogonadism. Screening for infections was negative. The immunological assessment for antinuclear antibodies, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were negative. Standard radiography showed bilateral wrist carpitis. The olfactory bulb was present and normal by cerebral magnetic resonance imaging. The diagnosis of systemic juvenile idiopathic arthritis associated with hypogonadotropic hypogonadism, probably related to delayed puberty, was retained. A therapy combining corticosteroid, methotrexate for arthritis, and hormone replacement with testosterone led to regression of arthritis, biological inflammatory syndrome, and hypogonadism. The presence of rheumatic disease in this context of hypogonadism, regardless of its cause, is mainly associated with very low testosterone levels and the presentation of arthritis in these patients tends to be more severe.
33259155 2020 Jul Immune mediated immunological disorders comprise of a group of common conditions that affects the immunomodulatory pathways resulting in lasting and disabling inflammatory conditions. Rheumatological disorders such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory conditions that affect predominantly the musculoskeletal system leading to pain, disability, functional impairment and lowered health related quality of life (HrQoL).(,) Treatment of these disorders aim at symptom management and to prevent and control joint and organ damage. They include corticosteroids, non-steroidal anti-inflammatory agents and disease-modifying antirheumatic drugs (DMARDs). Conventional DMARDs (cDMARDs) like methotrexate, sulfasalazine and hydroxychloroquine target the immune pathways, and have been used in early and long-term management of rheumatological disorders. Biologic DMARDs (bDMARDs) and janus kinase inhibitors target the molecules in the inflammatory pathway, thereby suppressing inflammation in RA, PsA and AS among other conditions. The clinical superiority of bDMARDs compared to placebo in rheumatological disorders have been established.(,). Among bDMARDs, tumor necrosis factor-alpha (TNF-α) inhibitors like adalimumab (ADA), infliximab (INF), etanercept (ETN), golimumab (GOL), and certolizumab pegol (CTZ) are approved for used in RA, PsA and AS.(,) In addition, interleukin-6 inhibitors like tocilizumab (TOC) and sarilumab (SAR) and T-cell stimulation blocker, abatacept (ABA) are used for RA, In PsA, secukinumab (SEC) is approved for use, and in AS ixekizumab (IXE) and SEC are also approved.(,) A janus kinase inhibitor, tofacitinib (TOF), is also approved for use in patients with RA. There is a scarcity of head-to-head trials comparing the clinical effectiveness of bDMARDs with each other. bDMARDs and targeted DMARDs being expensive, long term treatments with these agents will result in increased healthcare expenditure.(,) Thus, in the absence of comparative evidence, cost is a major determinant factor in the choice of bDMARDs. The objective of this report is to summarize the evidence regarding the comparative efficacy of ADA compared with other bDMARDs and tofacitinib in patients with rheumatological disorders.
32598110 2020 Mar Upadacitinib is a Janus kinase (JAK) inhibitor (also referred to as a targeted synthetic disease-modifying antirheumatic drug [tsDMARD] in practice), indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. The recommended dose of upadacitinib is 15 mg daily as monotherapy or combination therapy. At the sponsor-submitted price of $48.68 per 15 mg tablet, the annual treatment cost is $17,770. The sponsor submitted a cost-utility analysis that considered upadacitinib as initial treatment for moderate-to-severe RA after an inadequate response or are intolerant to either a conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR population) or a biologic disease-modifying antirheumatic drug (bDMARD-IR population). The sponsor’s analysis was conducted from the perspective of a Canadian publicly funded health care payer over a five-year time horizon. Comparators included csDMARDs, bDMARDs, and other tsDMARDs. The pharmacoeconomic submission was based on a Markov model, where treatment response was evaluated using the American College of Rheumatology (ACR) response criteria. The model was composed of four main health states after the evaluation of initial treatment: 20% improvement in ACR criteria (ACR20); 50% improvement in ACR criteria (ACR50); 70% improvement in ACR criteria (ACR70); and lack of adequate treatment response (i.e., did not achieve minimum of ACR20). Patients who had an inadequate response or discontinued treatment owing to a serious adverse event (SAE) could receive a subsequent treatment and transition to any of the previously mentioned health states. If an adequate response was not achieved on subsequent treatment, patients received best supportive care (BSC), the prior therapy (bDMARD or tsDMARD) which patients achieved the best treatment effect. A sponsor-commissioned network meta-analysis (NMA) was submitted and informed the comparative ACR response at weeks 12 and 24. SAEs were incorporated on the basis of an NMA previously conducted by CADTH4 and updated to include upadacitinib and other missing comparators. Long-term discontinuation was included in the model owing to a loss of treatment effect over time. Health state utility values for ACR response and nonresponse were based on Health Assessment Questionnaire (HAQ) scores mapped to the Health Utility Index 3 (HUI-3) tool. In the sponsor’s base case, upadacitinib + csDMARD was associated with both higher total costs and quality-adjusted life-years (QALYs) when compared to csDMARD monotherapy in both target populations. In the csDMARD-IR population, the preferred option is csDMARD monotherapy if the decision-maker’s willingness to pay (WTP) is below $74,979 per QALY, infliximab 3 mg/kg + csDMARD if the decision-maker’s WTP is between $74,979 and $80,897 per QALY, etanercept 50 mg + csDMARD if the decision-maker’s WTP is between $80,897 and $107,659 per QALY, and upadacitinib + csDMARD if the decision-maker’s WTP is more than $107,659 per QALY. In the bDMARD-IR population, the preferred option is a csDMARD if the decision-maker’s WTP is below $104,193 per QALY, upadacitinib + csDMARD if the decision-maker’s WTP is between $104,193 and $303,516 per QALY, and tocilizumab 8 mg/kg + csDMARD if the decision-maker’s WTP is more than $303,516 per QALY. Other treatments were dominated or extendedly dominated.
32043832 Predicting Remission Among Patients With Rheumatoid Arthritis Starting Tocilizumab Monothe 2020 Feb OBJECTIVE: Most patients with rheumatoid arthritis (RA) strive to consolidate their treatment from methotrexate combinations. The objective of this analysis was to identify patients with RA most likely to achieve remission with tocilizumab (TCZ) monotherapy by developing and validating a prediction model and associated remission score. METHODS: We identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remission was defined as a Clinical Disease Activity Index score less than 2.8 at 24 weeks post randomization. We used logistic regression to assess the association between each predictor and remission. After selecting variables and assessing model performance in the derivation data set, we assessed model performance in the validation data set. The cohorts were combined to calculate a remission prediction score. RESULTS: The variables selected included younger age, male sex, lower baseline Clinical Disease Activity Index score, shorter RA disease duration, region of the world (Europe and South America [increased odds of remission] versus Asia and North America), no previous exposure to disease-modifying antirheumatic drugs and/or methotrexate, lower baseline Health Assessment Questionnaire Disability Index score, and baseline hematocrit. The area under the receiver operating characteristic curve was 0.739 in the derivation data set and 0.756 in the validation data set. Patients were categorized into three remission prediction categories based on the remission prediction score: 40% in the low (less than 10% probability of remission), 45% in the intermediate (10%-25% probability), and 15% in the moderate remission prediction category (greater than 25% probability). CONCLUSION: We used easily accessible factors to develop a remission prediction score to predict RA remission at 24 weeks after initializing TCZ monotherapy. These results may provide guidance to clinicians tailoring treatment options based on clinical characteristics.
33073933 Evaluation of Improvement in Skin and Nail Psoriasis in Bio-naïve Patients With Active Ps 2020 Nov OBJECTIVE: To evaluate whether intravenous (IV) golimumab produces improvements in skin and nail symptoms that are concomitant with improvements in quality of life (QoL) and joint symptoms in patients with psoriatic arthritis. METHODS: Patients were randomized to either IV golimumab 2 mg/kg at weeks 0, 4, then every 8 weeks (q8w) through week 52 or placebo at weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at weeks 24, 28, and then q8w through week 52. Assessments included Psoriasis Area and Severity Index (PASI), modified Nail Psoriasis Severity Index (mNAPSI), Dermatology Life Quality Index (DLQI), and American College of Rheumatology (ACR) rheumatoid arthritis response criteria. RESULTS: Through week 24, achievement of PASI 75/90/100 responses (P ≤ .0098) and mean improvements in mNAPSI (-11.4 vs -3.7; P < .0001) and DLQI (-9.8 vs -2.9; P < .0001) were significantly greater with golimumab versus placebo. Responses were maintained in patients treated with golimumab through week 52. In placebo-crossover patients, increases in the proportion of patients achieving PASI 75/90/100 responses were observed from weeks 24 to 52, and mean improvements in mNAPSI (from -3.7 to -12.9) and DLQI (from -2.9 to -7.8) increased from weeks 24 to 52. Simultaneous achievement of PASI and DLQI responses, PASI and ACR responses, and mNAPSI and DLQI responses were also observed. Similar responses were observed for all assessments regardless of concomitant methotrexate use. CONCLUSION: Improvements in skin and nail psoriasis symptoms with IV golimumab in patients with psoriatic arthritis were concomitant with improvements in QoL and arthritis disease activity through 1 year.
31852268 Infection risk in patients undergoing treatment for inflammatory arthritis: non-biologics 2020 Feb Introduction: Despite the therapeutic effectiveness of biologics targeting immune cells or cytokines in patients with inflammatory arthritis, which reflects their pathogenic roles, an increased infection risk is observed in those undergoing biological treatment. However, there are limited data regarding the comparison of infection risks in inflammatory arthritis patients treated with non-biologics (csDMARDs), biologics (bDMARDs), including tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors, or targeted synthetic (ts)DMARDs.Areas covered: Through a review of English-language literature as of 30 June 2019, we focus on the existing evidence on the risk of infections caused by bacteria, Mycobacterium tuberculosis, and hepatitis virus in inflammatory arthritis patients undergoing treatment with csDMARDs, bDMARDs, or tsDMARDs.Expert opinion: While the risks of bacterial and mycobacterial infection are increased in arthritis patients treated with csDMARDs, the risks are further higher in those receiving bDMARDs therapy, particularly TNF inhibitors. Regarding HBV infection, antiviral therapy may effectively prevent HBV reactivation in patients receiving bDMARDs, especially rituximab. However, more data are needed to establish effective preventive strategies for HBsAg-negative/HBcAb-positive patients. It seems safe to use cyclosporine and TNF inhibitors in patients with HCV infection, while those undergoing rituximab therapies should be frequently monitored for HCV activity.Abbreviations: ABT: abatacept; ADA: adalimumab; AS: ankylosing spondylitis; bDMARDs: biologic disease-modifying anti-rheumatic drugs; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; CS: corticosteroids; CsA: cyclosporine A; csDMARDs: conventional synthetic disease-modifying anti-rheumatic drugs; CZP: certolizumab; DAAs: direct-acting antiviral agents; DM: diabetes mellitus; DOT: directly observed therapy; EIN: Emerging Infections Network; ETN: etanercept; GOL: golimumab; GPRD: General Practice Research Database; HBV: hepatitis B virus; HBVr: HBV reactivation; HBsAg+: HBsAg-positive; HBsAg-/anti-HBc+: HBsAg-negative anti-HBc antibodies-positive; HCV: hepatitis C virus; HCQ: hydroxychloroquine: IFX: infliximab; IL-6: interleukin-6; JAK: Janus kinase; LEF: leflunomide; LTBI: latent tuberculosis infection; mAb: monoclonal antibody; MTX: methotrexate; OR: odds ratio; PsA: psoriatic arthritis; PMS: post-marketing surveillance; RA: rheumatoid arthritis; TNF: tumor necrosis factor; TNFi: tumor necrosis factor inhibitor; SCK: secukinumab; SSZ: sulfasalazine; TOZ: tocilizumab; RCT: randomized controlled trial; RR: relative risk; RTX: rituximab; 3HP: 3-month once-weekly isoniazid plus rifapentine; TB: tuberculosis; tsDMARDs: targeted synthetic disease-modifying anti-rheumatic drugs; UTK: ustekinumab; WHO: World Health Organization.
32911791 Multicentric Reticulohistiocytosis Exhibiting Positive HLA-B*07 and HLA-B*08: A Case Repor 2020 Sep 8 Multicentric reticulohistiocytosis (MRH) is a rare cause of destructive inflammatory arthritis involving both small, as well as larger joints. We report the case of a 40-year-old Caucasian female with a family history of neoplasia who was referred to our service witha two-month history of inflammatory joint pain. On examination, the patient had inflammatory arthritis, mainly involving the peripheral joints, sacroiliac joint pain, and numerous papulonodular mucocutaneous lesions, including periungual "coral beads". Imaging tests revealed erosive arthritis with synovitis and tenosynovitis, sacroiliac joint changes, as well as papulonodular mucosal lesions in the nasal vestibule, the oropharyngeal mucosa, and supraglottic larynx. She tested positive for HLA-B*07 (Human Leukocyte Antigen B*07) and HLA-B*08, ANA (antinuclear antibodies), RF (rheumatoid factor), anti-Ro52, anti-SSA/Ro, and anti-SSB/La antibodies. The skin biopsy was suggestive of MRH, showing a histiocyte infiltrate and frequent giant multinucleated cells. The patient exhibited favorable outcomes under Methotrexate, then Leflunomide. However, she displayed worsening clinical symptoms while under Azathioprine. To our knowledge, this is the first case of MRH to exhibit positive HLA-B*07 together with HLA-B*08. The rarity of MRH, its unknown etiology and polymorphic clinical presentation, as well as its potential neoplastic/paraneoplastic, and autoimmune nature demand extensive investigation.
32258416 Streptococcus Pneumoniae-associated Thrombotic Microangiopathy in an Immunosuppressed Adul 2020 A 62-year-old male who was receiving prednisolone and methotrexate for scleroderma and rheumatoid arthritis complained of diarrhea and vomiting, and was transferred to our hospital for detailed examination and treatment of renal dysfunction and thrombocytopenia. Hemolytic anemia and crushed erythrocytes were found during the patient's course; therefore, we suspected thrombotic microangiopathy (TMA). His ADAMTS13 activity was 60.3% and his ADAMTS13 inhibitor was under 0.5. In addition, his blood culture was positive for Streptococcus pneumoniae, and we finally diagnosed Streptococcus pneumoniae-associated TMA (pTMA). The patient was treated with antibiotics and hemodialysis. The patient recovered and was discharged on the 45(th) hospital day. Adult pTMA cases are remarkably rare. We herein report a successfully treated adult case of pTMA.