来氟米特治疗类风湿关节炎疗效评价

目的：通过Ⅱ型随机对照临床试验比较研究药物来氟米特（LEF）和阳性对照甲氨喋呤（MTX）治疗类风湿关节炎（RA）临床疗效和安全性,旨在科学地评价LEF在治疗RA中的作用。方法：本试验为单盲随机对照临床研究。50例活动性RA病人随机分入LEF组（24例）和MTX组（26例）,分别服用LEF20mg/d 安慰剂（C）和MTX15mg/每周 安慰剂（B）3个月。试验开始4周同时应用非甾体抗炎药Wu丙嗪。所有病人在治疗前和试验结束后测定临床指标包括休息痛、晨僵、据力、关节压痛数/指数、关节肿胀数/指数、ESR、CRP、病人/医师评价等。结果：治疗12周后,LEF组总有效率和显效率分别为100%和83.33%,MTX组分别为96.15%和73.08%(P＜0.05)。两组病人治疗12周主要临床指标均较治疗前明显改善,且除晨僵外两组间改善值和改善百分率比较明显差别。LEF组不良反应发生率为83%,MTX组为23.08%(P=0.012)。病人对LEF耐受性好,两组病人对药物的耐受性有明显的差异（P=0.043)。结论：LEF治疗RA病人12周,其疗效与MTX相似,未发现不良反应,病人耐受性好。     

来氟米特治疗类风湿关节炎疗效评价

目的：通过ＩＩ期随机对照来氟米特（ＬＥＦ）和甲氨喋呤（ＭＴＸ）治疗类风湿关节炎（ＰＡ）临床疗效和安全性,旨在科学地评价ＬＥＦ在治疗ＲＡ中的作用。方法：本试验为潼单盲随机对照临床研究。５０例活动性ＲＡＵ现人随机分入ＬＥＦ组（２４例）和ＭＴＸ组（２６例）,分别服用ＬＥＦ２０ｍｇ／ｄ＋安慰剂（Ｃ）和ＭＴＸ１５ｍｇ／每周＋安慰剂（Ｂ）３个月,试验开始４周同时应用非甾体抗炎药恶丙嗪,所有病人在治疗前和试验结束后测定临床指标包括何处痛、晨僵、握力、关节压痛数／指数、关节肿胀数／指数、ＥＳＲ、ＣＲＰ、病人／医师评价等。结果：治疗１２周后,ＬＥＦ组总有效率和显效率分别为１００％和８３．３３％,ＭＴＸ组分别为９６．１５％和７３．０８％（Ｐ〈０．０５）。两组病人治疗１２周主要临床指标均较治疗前明显改善。且除晨僵外两组间改善值和改善     

Randomized Controlled Trial Comparing 2 Different Starting Doses of Methotrexate in Rheumatoid Arthritis

Purpose

Methotrexate (MTX) remains the gold standard disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). Few studies have compared different starting doses of MTX in RA. We hypothesized that starting with a higher MTX dose may be more effective but associated with more adverse effects. We compared a starting dose of 7.5 versus 15 mg per week of MTX followed by similar fast escalation.

Methods

This was an open-label (blinded assessor), parallel-group, randomized controlled trial that included RA patients aged 18 to 65 years, not on MTX, and having active disease (Disease Activity Score for 28 joints using 3 variables [DAS28(3)] ≥5.1). Patients were randomized to receive MTX at a starting dose of 7.5 mg (group 1) or 15 mg (group 2) per week. The dose of MTX was escalated by 2.5 mg every 2 weeks to a maximum of 25 mg. Patients were seen every 4 weeks, and dose escalation was continued if DAS28(3) was >2.6 and there were no laboratory abnormalities (transaminitis [>2 × upper limit of normal] or cytopenia). The primary endpoint was change in disease activity at 12 weeks (assessed by using the DAS28[3]). Secondary endpoints were patient withdrawals and episodes ofcytopenia or transaminitis. Adverse effects were ascertained by using a questionnaire. Both intention-to-treat and per-protocol analyses were performed.

Findings

We enrolled 100 patients (female:male ratio, 78:22) with a mean (SD) age of 43.6 (10.8) years and a disease duration of 4.7 (4.8) years. At baseline, patients had a mean DAS28(3) of 6.2 (0.7) and a Health Assessment Questionnaire score of 1.3 (0.6). Group 1 (7.5 mg) and group 2 (15 mg) included 47 and 53 patients, respectively, with no significant differences in baseline characteristics. At 12 weeks, the mean dose of MTX reached was 17.3 (4.6) mg in group 1 and 23.6 (3.0) mg in group 2 (P < 0.001). The 2 groups had a similar number of patient withdrawals. The mean change in DAS28(3) at 12 weeks in group 1 (–0.47 [0.86]) and group 2 (–0.55 [0.79]) was not significantly different (P = 0.60). The change in the Health Assessment Questionnaire score was also similar in the groups. The frequency of episodes of transaminitis (6 and 7; P = 0.8) and cytopenia (1 and 2; P = 0.9) did not differ significantly between groups 1 and 2, respectively. Results remained the same according to the per-protocol analysis. Among adverse effects, nausea was more common in group 2 compared with group 1 (relative risk, 1.6 [95% CI, 1.1–2.2]).

Implications

There were no significant differences in efficacy between the 2 starting doses of MTX. The fast escalation of dose in both groups may have blunted any advantage of starting at a higher dose. Nausea occurred more commonly in patients started on 15 mg of MTX. We suggest longer trials to confirm our findings. ClinicalTrials.gov identifier: NCT01404429.     

Methotrexate Dose in Patients With Early Rheumatoid Arthritis Impacts Methotrexate Polyglutamate Pharmacokinetics,Adalimumab Pharmacokinetics,and Efficacy: Pharmacokinetic and Exposure-response Analysis of the CONCERTO Trial

Purpose

Methotrexate (MTX) and adalimumab are well-recognized treatments of rheumatoid arthritis (RA), the efficacy of which may be driven by intracellular polyglutamates (PGs). The aim of this analysis was to characterize MTX PG concentrations and adalimumab pharmacokinetics in the CONCERTO trial. In addition, the relationships between MTX dose/pharmacokinetics, adalimumab pharmacokinetics, and efficacy were evaluated.

Methotrexate: A Gold Standard for Treatment of Rheumatoid Arthritis

ABSTRACT

Rheumatoid arthritis (RA) is a painful, debilitating disease characterized by inflammation of the joints, with the proliferation of the synovium and the progressive erosion of cartilage and bone. The treatment of RA is still unsatisfactory, but a number of powerful disease-modifying antirheumatic drugs have become available, such as methotrexate (MTX). Even in the current era of biological targeted therapies, MTX remains the initial preferred antirheumatic drug and is considered to be the gold standard for treatment of RA. The combination of its perceived efficacy, acceptable safety profile, and low cost, as well as decades of clinical experience, makes MTX the cornerstone of treatment for RA and the anchor drug in combination with various biological agents. In this review, the authors aim to summarize the research done in the field of drug delivery systems of MTX according to its routes of administration for treatment of RA. The last part of the review addresses combination therapy with MTX and future direction in the drug delivery of MTX. This review also provides the reader with a general overview of RA and its therapeutic strategies with respect of MTX, which may bring uniformity in medical practice for effective management of RA.     

甲氨喋呤联合雷公藤多甙片治疗类风湿性关节炎疗效及安全性观察

目的评价甲氨喋呤（MTX）联合雷公藤多甙片治疗类风湿性关节炎的疗效及安全性。方法将42例类风湿性关节炎患者随机分为两组：甲氨喋吟治疗组20例,接受甲氨喋吟10mg／周;甲氨喋吟联合雷公藤多甙片治疗组22例,接受甲氨喋吟10mg／周、雷公藤多甙片60mg／d。观察治疗3个月两组患者病情改善情况及药物不良反应。结果按美国风湿病协会（ACR）类风湿性关节炎改善标准,39例完成3个月的治疗,MTX组19例完成患者中症状改善（达ACR20或以上）15例,总有效率78．9％。联合组20例患者病情改善16例,总有效率为80．0％,两组比较差异有显著性（P〈0．05）。并且两组晨僵、关节肿痛数、关节压痛数、患者对疾病活动性的总体评价、医生对疾病活动性的总体评、红细胞沉降率、C反应蛋白等临床指标差异均有统计学意义。两组的不良反应比较,差异无统计学意义（P〉0．05）。结论甲氨喋吟联合雷公藤多甙片治疗类风湿性关节炎的疗效优于单用甲氨喋吟治疗,且安全性好。     

Joint Mobilization of the Hands of Patients With Rheumatoid Arthritis: Results From an Assessor-Blinded,Randomized Crossover Trial

ObjectiveThe purpose of this study was to assess the clinical feasibility and effectiveness of manual mobilization of the hands of patients with rheumatoid arthritis (RA).MethodsA total of 320 individual hand joints were evaluated after recruiting an experimental research group of 12 participants with RA and, for clinical comparability, 8 participants with hand osteoarthritis (OA). One hand per participant was randomized to receive weekly low-grade (I-II) Kaltenborn manual mobilization, using passive sustained stretch of the metacarpophalangeal (MCP) joints II to V by licensed manual therapists. After 2 weeks, the randomized treated hand was crossed over to control (untreated) during weeks 3 to 4 and vice versa. Final assessment was at 2 months, which was 1 month after the last treatment at week 4. Primary hand outcomes included pain by visual analog scale, tender or swollen joint count, and presence of Doppler signal or synovial fluid and radiographic joint space by musculoskeletal ultrasound.ResultsIn the RA group, both the initially randomized treated hand and the contralateral hand improved significantly from baseline to crossover to follow-up at 2 months (pain outcomes and Doppler signal, P < .050; synovial fluid and MCP joint space, P ≤ .001). Hand pain and MCP joint space also improved significantly in OA. There were no dropouts or reported adverse events in either the RA or OA group.ConclusionIn this study, manual mobilization of the hands of patients with RA was shown to be feasible, safe, and effective to integrate into specialized healthcare.     

Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter,Randomized, Double-Blind,Parallel Phase III Clinical Study

PurposeThe aim of this study was to evaluate the blood pressure–lowering and cholesterol-lowering effects of a fixed-dose combination therapy using candesartan (CND)/rosuvastatin (RSV) compared with CND or RSV monotherapy in patients with hypertension and hypercholesterolemia.MethodsThis study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of total cholesterol, triglycerides, HDL-C, non–HDL-C, apolipoprotein B, apolipoprotein A-I, high-sensitivity C-reactive protein, and glucose metabolic indices, including percentage changes of the homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and hemoglobin A_1c. Tolerability of combination therapy was compared with other monotherapy groups.FindingsThe percentage changes of LDL-C were ?48.6% (from 157.2 to 80.1 mg/dL) in the RSV group and ?49.8% (from 160.2 to 78.9 mg/dL) in the CND/RSV group from baseline to the end of 8 weeks of treatment. Mean SBP and DBP were significantly decreased in the CND/RSV and CND groups after 8 weeks (P < 0.001 for all); however, no significant differences were found between the 2 groups. Total cholesterol levels, triglycerides, non–HDL-C, and apolipoprotein B were significantly reduced in the CND/RSV and RSV groups, with no significant differences between the groups compared with the CND group (P < 0.001 for all). The percentage changes of HOMA-IR, adiponectin, and hemoglobin A_1c had no significant differences between the combination groups and monotherapy groups. However, in a 2-sample t test, HOMA-IR was significantly decreased in the CND/RSV group compared with the RSV group in nondiabetic patients (mean [SD] percentage change of HOMA-IR, ?8.7% [37.6%] vs 17.1% [53.1%]; P = 0.048). There were no significant differences in metabolic indices between the diabetic groups. Adverse events in the CND/RSV group were similar to those in the monotherapy group.ImplicationsOnce-daily fixed-dose combination therapy with CND/RSV is an effective, tolerable, convenient treatment option for patients with essential hypertension and hypercholesteremia. ClinicalTrials.gov identifier: NCT02770261.     

Calprotectin in patients with chronic rheumatoid arthritis correlates with disease activity and responsiveness to methotrexate

Objective: Calprotectin (myeloid-related protein 8/14) is elevated in inflammatory diseases and a correlation of serum calprotectin and disease activity in rheumatoid arthritis (RA) has been shown. In this study, we investigated plasma calprotectin as a disease marker in patients with chronic RA treated with methotrexate (MTX) monotherapy and compared plasma calprotectin with C-reactive protein (CRP) in this matter.

Methods: Seventy-six patients with chronic RA were included in this open prospective study and of these 40 were included prior to initiation of MTX therapy. The patients were followed with laboratory and clinical parameters for 52–56?weeks. Plasma calprotectin was analyzed at the start of study and at various intervals. Radiographic evaluation was performed at baseline and after 17.2?months and progression in joint destruction was measured with Larsen score. The response to MTX was evaluated according to the American College of Rheumatology criteria.

Results: Patients starting MTX treatment had significantly higher levels of plasma calprotectin compared to patients well established on MTX therapy (p?=?.008). Among the 40 patients naive to MTX, 25 responded to MTX therapy and serum calprotectin decreased significantly in these patients (p?=?.0007). The radiographic damage showed no relation to calprotectin.

Conclusions: Plasma calprotectin is associated with disease activity in patients with chronic RA and is more strongly correlated to MTX response compared to CRP. The role of calprotectin as a disease marker is promising and the advantages compared to CRP needs to be further investigated.     

Efficacy and Safety of Fenofibrate-Statin Combination Therapy in Patients With Inadequately Controlled Triglyceride Levels Despite Previous Statin Monotherapy: A Multicenter,Randomized, Double-blind,Phase IV Study

PurposeResidual cardiovascular risk reduction by fenofibrate in patients with high serum triglyceride (TG) levels despite previous statin monotherapy is not well characterized. The purpose of this study was to evaluate the efficacy and safety of a combination of choline fenofibrate and statin in patients with inadequately controlled TG levels despite previous statin monotherapy.MethodsThis prospective, multicenter, randomized, double-blind study was conducted in Korea. A total of 133 patients with controlled LDL-C but elevated TG levels, already receiving statin monotherapy, were enrolled in the study, which was conducted from July 2018 to December 2019. Patients were randomly assigned to receive combination therapy with choline fenofibrate and statin or statin monotherapy in a 1:1 ratio. After 8 weeks of treatment, the lipid profiles and safety parameters of the patients in the 2 groups were compared.FindingsThe study included 127 patients (64 in the combination group and 63 in the control group) older than 19 years. After 8 weeks of therapy, mean serum TG levels significantly decreased from 269.8 to 145.5 mg/dL (P < 0.0001) in the combination therapy group, whereas no significant changes occurred in the statin monotherapy group (from 271.1 to 280.5 mg/dL). Contrarily, the mean serum HDLC levels significantly increased from 45.0 to 50.4 mg/dL (P = 0.0004) in the combination therapy group, whereas there were no significant changes in the monotherapy group (from 44.3 to 44.7 mg/dL). There were no additional serious adverse events in the combination therapy group compared with the statin monotherapy group.ImplicationsThe combination therapy using choline fenofibrate and statin was found to be effective in serum TG control and likely tolerable in patients with high TG levels despite statin monotherapy. A larger study, conducted for a longer duration, is needed to evaluate the effectiveness of this combination in reducing cardiovascular risk. ClinicalTrials.gov identifier: NCT03874260.     

A Prospective,Observational Study of Use Combination Silodosin 8 mg Plus Serenoa Repens,Urtica Dioica,Cucurbita Pepo (Rotaprost) Compared With Silodosin 8 mg Alone in Treatment Patients with Benign Prostate Hyperplasia

BackgroundBenign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms (LUTS) in older men. Nowadays, there are several plant extracts used for the treatment of LUTS due to BPH.ObjectiveThe aim of this study is to compare the effect of combining silodosin 8 mg with Serenoa repens, Urtica dioica, Cucurbita pepo (Rotaprost 530 mg) compared to silodosin 8 mg and Rotaprost 530 mg alone in patients with LUTS/BPH.MethodsFour hundred five men with symptomatic BPH were recruited for the study from June 2020 to January 2021. Three hundred eighty-nine patients were followed up for 6 months. All participants provided written informed consent. This prospective study included analysis of three treatment groups: Group I patients (n = 130) received a combination of silodosin 8 mg and Rotaprost 530 mg (containing a dry extract of Serenoa repens 80 mg, a dry extract of Urtica dioica 150 mg, a dry extract of Cucurbita pepo seeds 200 mg, zinc (in the form of zinc picolinate) 0.105 mg, and selenium (as sodium selenite) 22.5 µg); the group II (n = 129) received silodosin 8 mg alone, and the group III (n = 130) received Rotaprost 530 mg alone. Outcomes were measured by changes from baseline in International Prostate Symptom Score (IPPS) total score, PSA value, prostate volume, residual urine after urination, and maximum flow rate. Statistical significance was set at P < 0.05.ResultsIn group I, IPSS, prostate volume, and maximum urinary flow rate (Qmax) improved significantly (P < 0.05) compared with groups II and III during follow-up. Prostate volume in group I showed a significant decrease only during 6 months of therapy (P < 0.05). No serious adverse effects were registered in the three groups.ConclusionCombination therapy with silodosin 8 mg significantly reduced LUTS/BPH, Qmax, and prostate volume compared with silodosin 8 mg alone. Rotaprost 530 mg can also reduce PSA by at least 20.6?25.7% after 6-months of treatment.     

Comparative Multidatabase Analysis of Dosing Patterns and Infusion Intervals for the First 12 Infliximab Infusions in Patients With Rheumatoid Arthritis

BackgroundAccording to prescribing information for rheumatoid arthritis (RA) treatments in the United States, infliximab should be administered at weeks 1, 2, 6, and then every 8 weeks starting at a 3-mg/kg dose, with flexible dosing up to 10 mg/kg and/or every 4 weeks based on clinical response.ObjectiveThis study evaluated dosing and intervals of the first 12 infliximab infusions in patients with RA across multiple large administrative databases.MethodsData were obtained from 4 databases: HealthCore Integrated Research Database (HIRD), IMS LifeLink Health Plan Claims Database (IMS Lifelink), Premier Perspective Database (PPD), and Wolters Kluwer Pharma Solutions (WKPS). Patients were aged ≥18 years, diagnosed with RA, and naive to biologic therapy. Patients with other select inflammatory conditions were excluded. The induction period included infusions 1 through 3; the maintenance period included infusions 4 through 12.ResultsObserved dosing patterns from the HIRD, IMS LifeLink, PPD, and WKPS databases demonstrated minimal dose increases from the first infusion (93.5, 103.3, 58.8, and 73.2 mg, respectively) and from the first maintenance infusion (69.1, 64.3, 45.7, and 45.7 mg, respectively) to the highest dose during the first 12 infusions. The mean number of days between infusions in the maintenance period ranged from 53.3 to 63.5 in HIRD, 53.7 to 60.3 in IMS LifeLink, 53.4 to 59.4 in PPD, and 52.3 to 55.0 in the WKPS database.ConclusionData from multiple databases of patients with RA suggest that, in clinical practice, infliximab dosing and intervals are consistent with FDA prescribing information and remain relatively stable during the first 12 infusions.     

Therapeutic efficacy of experimental rheumatoid arthritis with low-dose methotrexate by increasing partially CD4CD25Treg cells and inducing Th1 to Th2 shift in both cells and cytokines

Low-dose methotrexate (MTX), a traditional folate antagonist and disease-modifying antirheumatic drug administered weekly either alone or as combination therapy, is widely accepted as the gold standard in rheumatoid arthritis (RA) treatment. Although its mechanism of action in RA is still poorly understood, MTX potentially acts via antiproliferative, anti-inflammatory, and/or immunosuppressive means. The therapeutic mechanisms and efficacy of low-dose MTX and the oral tolerance protein natural chicken type II collagen (nCCII) were compared in vitro and in vivo using an established collagen-induced arthritis (CIA) rat model. We used clinical visual scoring, radiographic X-ray analysis, histopathological examination, and sera anti-CII IgG measurements to determine the severity of disease with and without treatment. Low-dose MTX had significant clinical therapeutic efficacy against established CIA. Similar to nCCII, MTX mediated CIA by specific immunotolerant effects and not by nonspecific immunosuppression. The mechanism underlying the therapeutic efficacy could be at least partially attributed to the increased production of CD4⁺CD25⁺ Treg cells. These cells specifically downmodulated the T lymphocyte proliferative response to CCII but not PHA, induced a Th1-to-Th2 shift, downregulated Th1 cytokines, and upregulated both Th2 and Th3 cytokines. To the best of our knowledge, this is the first demonstration that low-dose MTX probably serves as a potent inducer of specific immunotolerance but not of nonspecific immunosuppression in the treatment of RA.     

Immediate Effects of Ankle Non-elastic Taping on Balance and Gait Ability in Patients With Chronic Stroke: A Randomized,Controlled Trial

ObjectiveThe purpose of this study was to determine the immediate effects of ankle non-elastic taping on balance and gait ability in patients with chronic stroke.MethodsThirty patients (inpatients and outpatients) with stroke were randomly assigned to 2 groups: the non-elastic taping group (n = 15) and the placebo-taping group (n = 15). Patients in the non-elastic taping group received Endura sports taping for their ankle joint, and patients in the placebo-taping group received Endura fix tape for their ankle joint. The Balance System SD assessed balance, and the GAITRite system assessed gait ability. We recorded measurements before and after intervention.ResultsThe non-elastic taping group showed a significant improvement in static and dynamic standing balance (P ≤ .001) after intervention; in addition, this group showed significant increases in the velocity, cadence, step length, and stride length of gait (P ≤ .001) after intervention. However, the placebo-taping group showed no significant improvements in standing balance and gait ability after intervention (P >.05). Furthermore, significant differences in static and dynamic standing balance, cadence, and velocity were observed between the 2 groups after intervention (P ≤ .001).ConclusionsOur results demonstrate that the application of ankle non-elastic taping is effective at improving balance and gait abilities in patients with stroke. Ankle non-elastic taping appears to be an effective method to facilitate active rehabilitation in patients with hemiplegia.     

Efficacy of amiodarone and voriconazole combination therapy in cutaneous leishmaniasis in the mice experimentally infected with Leishmania major

IntroductionThe aim of the present study was to evaluate in vitro and in vivo efficacy of combination therapy of amiodarone and voriconazole against Leishmania major and investigating immune and wound healing responses of cutaneous leishmaniasis to this combination therapy.Methods: For in vitro study, replication of L. major promastigotes and intracellular amastigotes were investigated in the presence and absence of amiodarone and voriconazole. Isobologram construction and calculation of the Fractional Inhibitory Concentration (FIC) were performed. After the appearance of ulcers on the base of tails of BALB/c mice, treatment was initiated by a combination of amiodarone at 40 mg/kg plus voriconazole at 30 mg/kg orally and glucantime at 60 mg/kg intraperitoneally for 28 consecutive days.Results: According to the concave isobologram and fractional inhibitory concentration <1, combination of amiodarone plus voriconazole had synergistic effects against L. major promastigotes and intracellular amastigotes. There were less inflammatory cells, more fibroblasts and more collagen deposition in tissue sections in the mice treated with combined drugs compared to the vehicle and untreated mice. Increased glutathione peroxidase activity and decreased malondialdehyde, Interleukin-6, and Tumor necrosis factor-α levels were detected in the combination therapy group in comparison to the vehicle and untreated groups.Conclusions: It seems a combination of amiodarone plus voriconazole can be a rational and promising therapeutic approach in the treatment of cutaneous leishmaniasis.     

Clinical Efficacy of Oral Linezolid Compared With Intravenous Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus-Complicated Skin and Soft Tissue Infections: A Retrospective, Propensity Score-Matched, Case-Control Analysis

BackgroundLinezolid is 100% bioavailable in oral and intravenous formulations. In a recent prospective, randomized, open-label, comparator-controlled, multicenter, phase 4 clinical trial in adults with complicated skin and soft tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA), linezolid achieved clinical and microbiologic success comparable to appropriately dosed intravenous vancomycin. Although patients were randomly assigned to receive linezolid or vancomycin, the protocol allowed patients to start therapy using oral or intravenous linezolid on the basis of investigator discretion and patient ability to tolerate oral medication.ObjectiveThe objective of this study was to assess the efficacy and tolerability of linezolid when administered orally in adults with cSSTI caused by MRSA. In this retrospective analysis, we examined data collected from the aforementioned trial to compare outcomes in patients who received either oral linezolid or intravenous vancomycin therapy.MethodsThis study analyzed outcomes in patients who received treatment for 7 to 14 days with either oral linezolid (600 mg q12h; n = 95) or intravenous vancomycin (15 mg/kg q12h, adjusted for creatinine clearance and trough concentration; n = 210). By design, these groups were not randomized. Propensity score matching on baseline variables was used to balance these groups by identifying a comparable group of patients who received vancomycin therapy and comparing them with patients who received oral linezolid therapy. Clinical and microbiologic success rates at the end of treatment and the end of the study (EOS) were then directly compared between the groups using matched-pair logistic regression. The tolerability of the 2 treatments (within this matched group) was also described.ResultsNinety-two patients with well-matched baseline characteristics were included in each treatment group. At EOS, the odds ratio for clinical success of oral linezolid therapy vs intravenous vancomycin therapy was 4.0 (95% CI, 1.3–12.0; P = 0.01), and the odds ratio for microbiologic success at EOS was 2.7 (95% CI, 1.2–5.7; P = 0.01). Overall rates of adverse events in each group were consistent with reported safety profiles for each drug.ConclusionA favorable clinical cure rate was achieved with oral linezolid therapy when compared with intravenous vancomycin therapy in propensity score–matched patients with cSSTI proved to be caused by MRSA. ClinicalTrials.gov Identifier: NCT00087490.     

Therapeutic Target Attainment of 3-Hour Extended Infusion of Meropenem in Patients With Septic Burns

PurposeThe aim of this prospective cohort study was to evaluate the therapeutic target attainment of 3-hour extended infusion of meropenem in patients with septic burns in the early and late periods of septic shock.MethodsMeropenem serum levels were determined by liquid chromatography from blood samples collected within 48 hours (early period) of therapy and 10 to 14 days afterward (late period). Pharmacokinetic properties were investigated by noncompartmental analysis, and the therapeutic target was defined as 100% of the time above the MIC (100%fT> MIC).FindingsFifteen patients with 90 measured meropenem concentrations were included. Throughout the entire course of antimicrobial therapy, the therapeutic target was attained against gram-negative pathogens with an MIC ≤ 2 mg/L. Pathogens with intermediate susceptibility to meropenem were only covered in the early phase of therapy.ImplicationsHigher-dose regimens or continuous infusions may be necessary to guarantee antimicrobial coverage of meropenem against less sensitive pathogens in patients with septic burns.     

Extracorporeal Shock Wave Therapy Combined With Oral Medication and Exercise for Chronic Low Back Pain: A Randomized Controlled Trial

ObjectiveTo compare extracorporeal shock wave therapy combined with oral medication and an exercise program vs sham treatment with medication and exercise for the treatment of chronic low back pain (CLBP).DesignRandomized controlled trial.SettingOutpatient clinic at a university hospital.ParticipantsEligibility criteria were age older than 18 years and duration of CLBP exceeding 3 months. Exclusion criteria were concurrent treatment or history of surgery for CLBP, cancer, fractures, infections, and disk degeneration.InterventionThe intervention group received extracorporeal shock wave therapy once a week for 4 weeks along with oral medications and an exercise program. The control group received sham extracorporeal shock wave therapy along with oral medications and an exercise program.Main Outcome MeasuresVisual analog scale and Oswestry Disability Index (ODI) were used to assess pain and disability at baseline and after 3 months.ResultsThe pain score in the intervention group (N=16) was 6.6 at baseline and 3.0 after 1 month (P<.0001) and 1.8 after 3 months (P<.0001). In the control group (N=16), the pain score was 6.8 at baseline, 4.6 after 1 month (P<.0001), and 1.1 after 3 months (P<.0001). ODI scores decreased significantly in both groups compared with baseline values (first month: P<.001, third month: P<.05). The mean ODI score did not differ significantly between the groups (P=.942).ConclusionExtracorporeal shock wave therapy combined with oral medication and exercise was safe and effective in the short-term treatment of chronic low back pain.     

N‐feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis

Many of disease‐modifying anti‐rheumatic drugs often have side effects at high doses and/or during long‐term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The aim of the study was to examine the effect of N‐feruloylserotonin (N‐f‐5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats. Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund′s adjuvant in Lewis rats. The experiment included healthy animals, arthritic animals without any drug administration, arthritic animals with administration of N‐f‐5HT in the oral daily dose of 15 mg/kg b.w., arthritic animals with administration of MTX in the oral dose of 0.3 mg/kg b.w. twice a week and arthritic animals treated with the combination of N‐f‐5HT and MTX. N‐f‐5HT in monotherapy reduced only activation of NF‐κB and did not have any significant effect on other parameters monitored. Low‐dose treatment of MTX decreased the level of IL‐1β and MCP‐1 on day 14 and activation of NF‐κB in liver without significant effect on other parameters. N‐f‐5HT and MTX combination showed both the anti‐arthritic (hind paw volume and arthritic score) and anti‐inflammatory effect (plasmatic levels of IL‐1β, IL‐17, MCP‐1, CRP, and activation of NF‐κB in liver). In combination with MTX, N‐f‐5HT markedly potentiated the therapeutic effect of MTX low dose, which resulted in significant improvement of all parameters measured. The findings showed that the combination therapy simultaneously decreased multiple markers of inflammation, a result crucial for future therapy of RA.     

Abatacept: a biologic immune modulator for rheumatoid arthritis

Introduction: Abatacept is a biologic drug that belongs to the class of T-cell co-stimulation modulators and is used for the treatment of rheumatoid arthritis (RA).

Areas covered: This article covers major randomized clinical trials and meta-analyses concerning abatacept in the treatment of RA, as identified in a Pubmed search. Scientific meeting abstracts describing long-term extension data of the identified trials are also included. Efficacy outcomes and the safety profile are the focus of this evaluation.

Expert opinion: Abatacept in combination with methotrexate (MTX) or other synthetic disease-modifying anti-rheumatic drugs (DMARD) has been proven effective for the treatment of RA in different groups of patients: with early RA and no prior exposure to DMARD; with DMARD-resistant RA; and with RA not responding to TNF-α-blocking agents. Significant reductions of disease activity are achieved, with 1-year remission rates reaching up to 41% of DMARD-naïve patients with early RA receiving a combination of abatacept plus MTX. Abatacept treatment has been shown to improve function and quality of life and to suppress radiographic progression. No major safety issues have emerged during clinical trials and long-term extensions. Therefore, abatacept is a drug with a favorable efficacy and safety profile, which may offer substantial benefits to RA patients.