Methotrexate Monotherapy In Patients Research Articles

Efficacy and safety of methotrexate plus hydroxychloroquine combination therapy vs. methotrexate monotherapy in the treatment of rheumatoid arthritis: A randomized controlled clinical trial.

To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study. At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05). In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Upadacitinib monotherapy versus methotrexate monotherapy in patients with rheumatoid arthritis: efficacy and safety through 5 years in the SELECT-EARLY randomized controlled trial

BackgroundTo evaluate the efficacy and safety of upadacitinib monotherapy versus methotrexate (MTX) monotherapy over 5 years among MTX-naïve patients with moderately to severely active rheumatoid arthritis (RA) in the long-term extension (LTE) of the phase 3 SELECT-EARLY trial.MethodsPatients were randomized to receive upadacitinib 15 mg or 30 mg or MTX. Patients who did not achieve CDAI remission and had < 20% improvement in tender and swollen joint counts at week 26 received rescue therapy (addition of MTX in the upadacitinib group and addition of upadacitinib in the MTX group). Efficacy assessments were evaluated over 5 years and are reported as observed (AO) for patients who received continuous monotherapy with upadacitinib 15/30 mg or MTX and by randomized group applying non-responder imputation (NRI). Treatment-emergent adverse events (TEAEs) per 100 patient-years were summarized over 5 years.ResultsOf 945 patients randomized and treated, 775 (82%) completed week 48 and entered the LTE on study drug. Higher proportions of patients consistently achieved disease activity targets over 5 years with upadacitinib than MTX. In AO analyses, 53%/59% of patients attained CDAI remission with upadacitinib 15/30 mg versus 43% with MTX at week 260. NRI analyses showed better CDAI, DAS28(CRP), and ACR responses with upadacitinib relative to MTX at week 260 (all comparisons, nominal P < .001). Upadacitinib treatment also resulted in numerically greater inhibition of structural joint progression through week 260 compared to MTX. Most TEAEs, serious AEs, and AEs leading to discontinuation were numerically higher in patients receiving upadacitinib 30 mg. Rates of serious infections, herpes zoster, creatine phosphokinase elevation, nonmelanoma skin cancer, and neutropenia were numerically higher with upadacitinib than MTX. The observed safety profile of upadacitinib over 5 years was consistent with earlier trial results and integrated phase 3 safety analyses.ConclusionsUpadacitinib showed better clinical responses versus MTX in patients with RA throughout the 5-year trial. Higher rates of several AEs were observed with upadacitinib, especially in the 30 mg group, compared to MTX. When used as monotherapy in MTX-naïve patients, the approved upadacitinib 15 mg dose showed better long-term efficacy versus MTX and an overall favorable benefit-risk profile.Trial registrationNCT02706873.

Retrospective Cohort Study Comparing Efficacy and Safety of Pharmacological Intervention and Phototherapy in Moderate to Severe Psoriasis Patients in a Real-World Setting

Abstract Methotrexate (MTX) is one of the first-line systemic treatment options in patients with moderate-to-severe plaque psoriasis and can be combined with narrow band UVB phototherapy (Nb-UVB). However, such a combination is rarely used for optimal duration due to safety and efficacy concerns. The aim of this study was to assess efficacy and safety of methotrexate (MTX) combination with low doses of Nb-UVB versus MTX monotherapy in patients with moderate-to-severe plaque psoriasis in a real-world setting. Retrospective psoriasis patient medical chart review was performed for the period from 2013 till 2019. The combination therapy group (Group 1, n = 74) received MTX 10 mg s/c once a week for four to six weeks and 311 nm UVB phototherapy according to the skin type and protocol of administration — three times a week; undergoing 10–24 procedures in the treatment course. The monotherapy group (Group 2, n = 57) was treated, using MTX as monotherapy 2.5 mg two times a day orally for five days (4–6 treatment courses in total). The combination therapy group achieved decrease of mean PASI at the end of the 2nd week of treatment by 38% vs monotherapy group 21%. Combination of low dose subcutaneous MTX and Nb-UVB therapy provides better treatment outcomes and normalisation of immunochemical parameters than for MTX monotherapy. This combination also showed a favourable tolerability profile.

Joint-level responses to tofacitinib and methotrexate: a post hoc analysis of data from ORAL Start

BackgroundRheumatoid arthritis (RA) has a variable impact on different synovial joints, with inflammation being more commonly observed in some joints than others. Emerging evidence suggests that the anatomical variation in pathophysiology could result in differential responses to treatments across the joints, both within and between modes of action. This analysis aimed to characterize joint-specific responses to tofacitinib and methotrexate monotherapy in patients with RA.MethodsThis was a post hoc analysis of data from the phase III trial ORAL Start (NCT01039688), in methotrexate-naïve patients with RA. A paired joint pathology score (PJPS), derived from bilateral tender/swollen joint counts, was calculated. The percentage change from baseline in PJPS (%∆PJPS) and treatment-specific responses (tofacitinib 5 and 10 mg twice daily [BID] vs methotrexate; tofacitinib 5 vs 10 mg BID) for each patient joint pair, except for those with baseline/post-baseline PJPS = 0, were calculated at month 3, month 6, and month 12. Radiographic progression was similarly assessed using the Modified Total Sharp Score at month 6 and month 12.ResultsIn methotrexate-naïve patients, differences in %∆PJPS demonstrated greater responses with tofacitinib vs methotrexate in most joint locations. Lesser responses with tofacitinib vs methotrexate were observed in most joints of the feet, particularly at month 12. Despite this, radiographic progression at month 12 was significantly worse in the foot (and metacarpophalangeal) joints of patients receiving methotrexate vs tofacitinib.ConclusionWe observed variation in joint-specific responses with tofacitinib and methotrexate monotherapy. Despite a proximal–distal efficacy gradient, with better clinical responses in the feet, patients receiving methotrexate monotherapy demonstrated more radiographic progression in the foot joints compared with those receiving tofacitinib. These findings suggest that body site- and therapy-specific characteristics may interact to produce differential treatment responses.Trial registrationClinicalTrials.gov, NCT01039688.

Risk of incident cardiovascular events with disease-modifying anti-rheumatic drugs among adults with rheumatoid arthritis: a nested case-control study.

This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged ≥18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively. In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54[1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses. The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA. Key Points • This study evaluated the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). • Findings suggest no differential CVD risk with DMARDs in combination with MTX or used individually compared with MTX monotherapy in patients with early RA. • Further efforts should focus on a better understanding of the mechanism of DMARD combination treatments with MTX in modifying CV risk.

P122 Changes in Serum Levels of Cytokines with Methotrexate Monotherapy in Active Rheumatoid Arthritis: Results from a Multicentre, Randomized Controlled Trial on Methotrexate Escalation In Rheumatoid Arthritis

Abstract Background/Aims Identification of novel biomarkers of disease activity and prediction of treatment response in rheumatoid arthritis (RA) is an area of active research. Reliable biomarkers of methotrexate (MTX) response in RA are yet to be identified. We sought to study the change in serum levels of IL-6, MMP-3, and TNF-α with MTX monotherapy in patients with active RA. Methods Patients with active RA (SJC≥2 and TJC≥4) not on DMARDs (except HCQ and low-dose prednisolone) who had been enrolled in the multicentre, parallel-group RCT comparing two different MTX escalation strategies in RA (MEIRA) were included. All these patients received MTX monotherapy started at 15 mg/week and escalated to 25 mg/week by 4-8 weeks. Serum levels of IL-6, MMP-3, and TNF-α were measured by ELISA before starting MTX and after 16 weeks of MTX therapy. Responders were defined as patients who achieved a EULAR good or moderate response (based on DAS28ESR-3v) at 16 weeks. Analyses were intention-to-treat. Results 16 weeks of MTX therapy led to a decline in serum levels of both MMP-3 (p = 0.03, n = 129) and IL-6 (p = 0.048, n = 151). The decline in IL-6 levels was seen only in MTX responders (p = 0.003), but not in non-responders, while the decline in MMP-3 levels was seen in both MTX non-responders (p = 0.015) and responders (p = 0.44) (Table 1). Baseline (pre-treatment) serum levels of both IL-6 and MMP-3 were similar between MTX responders and non-responders. Correlations of serum levels of IL-6 (but not MMP-3) with measures of disease activity (DAS28, tender joint count) were weak but significant at 16 weeks. Serum TNF-α levels (n = 137) were undetectable in a majority of patients (93%). Serum IL-6 was not detectable in 67 (44%) patients at baseline. Conclusion Although serum levels of both MMP-3 and IL-6 reduced significantly with MTX therapy, the decline of IL-6 was seen only in MTX responders but not in non-responders. Pre-treatment serum levels did not predict future MTX response or non-response. IL-6 levels also correlated weakly but significantly with disease activity. Serial measurement of serum IL-6 merits further exploration in larger studies as a potential biomarker of MTX response in RA. Disclosure S. Jain: None. V. Dhir: None. A. Aggarwal: None. R. Gupta: None. S. Maurya: None. B. Leishangthem: None. A. Khullar: None. S. Naidu: None. S.K. Sharma: None. A. Sharma: None. S. Jain: None.

Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial

ObjectivesTo investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.MethodsThis 52-week, phase 3, multicentre,...

A Randomized, Prospective Study to Compare the Efficacy and Safety of Omega-3 Fatty Acids as Additional Therapy to Methotrexate versus Methotrexate Monotherapy in the Management of Moderate to Severe Plaque Psoriasis

Psoriasis is a chronic, inflammatory, hyperproliferative, immune-mediated skin disorder, having a prevalence of 0.44-2.8% in India. Methotrexate is a widely used systemic regimen for moderate to severe psoriasis. Supplementation of omega-3 fatty acids has decreased the severity of the disease in some studies. This study aimed to assess the efficacy and safety of omega-3 fatty acids as an add-on to methotrexate versus methotrexate monotherapy in patients with moderate to severe plaque psoriasis. A total of 40 patients with moderate to severe plaque psoriasis were recruited in the study and randomized into two groups of 20 patients each. Group O received omega-3 fatty acids as add-on to methotrexate and Group M received methotrexate monotherapy. Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Physician’s Global Assessment (PGA) were assessed at baseline, 4 weeks, 8 weeks and 12 weeks of treatment. The adverse events were assessed throughout the study period. There was a significant decrease in PASI and DLQI scores from baseline to end of 12 weeks in both groups (p&lt;0.001) but the difference between the two groups was not significant (p&gt;0.05). A higher number of patients had a PGA score of 0 or 1 at the end of 12 weeks in Group O (60%) as compared to Group M (40%) but the difference between the groups was not significant (p=0.34). The treatment was well tolerated in both the groups, with most common adverse events being nausea, diarrhea and epigastric pain. This study showed that the treatment in both the groups was equally effective in decreasing the severity of psoriasis and was well tolerated.

Effectiveness and safety of methotrexate monotherapy in patients with Crohn's disease refractory to anti-TNF-α: results from the ENEIDA registry.

Methotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited. To assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti-tumour necrosis factor (anti-TNFα) drugs. A retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti-TNFα started on methotrexate monotherapy. Short-term effectiveness was assessed at 12-16weeks based on Harvey-Bradshaw index (HBI): clinical remission as HBI≤3 points and clinical response as HBI drop of≥3 points over baseline. Long-term effectiveness was defined as steroid-free methotrexate persistence from 12 to 16weeks until maximum follow up. Adverse events were recorded. Data were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti-TNFα agents. Short-term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long-term effectiveness was achieved in 82% and 74% at 12 and 24months respectively. In the multivariate analysis, non-remission at short term (vs remission) was associated with long-term failure (HR 2.58, 95%CI 1.95-3.68, P=0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation. The benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti-TNFα.

Factors predicting addition of disease-modifying antirheumatic drugs after initial methotrexate monotherapy in patients with rheumatoid arthritis.

We investigated factors predicting the addition of disease-modifying antirheumatic drugs (DMARDs) after an initial methotrexate (MTX) monotherapy in rheumatoid arthritis (RA) patients to support an early decision on the DMARDs addition. This retrospective cohort study included 311 patients who were diagnosed with RA and started on MTX monotherapy at Showa University Hospital, Japan. The outcome was addition of DMARDs after an initial MTX monotherapy at 6 months. Baseline patient characteristics were compared between the DMARDs addition and MTX monotherapy continuation groups, and significant independent predictive factors for the addition of DMARDs were selected using multivariate analysis. The median age of patients was 62 years (range 24-90), 170 patients (73%) were women, the median swollen 28-joint count (SJC28) was 3 (0-28), and the median tender 28-joint count (TJC28) was 5 (0-28). DMARDs were added in 65 (27.9%) patients. In the univariate analysis, higher TJC28 and SJC28, concomitant use of nonsteroidal anti-inflammatory drugs, and intra-articular glucocorticoid (GC) injection history were significantly associated with the DMARDs addition. In the multivariate analysis, by adding covariates to the variables identified in the univariate analysis, SJC28 (odds ratio [OR] 1.390 per 5 joints increase; 95% confidence interval [CI], 1.036-1.866) and intra-articular GC injection history (OR 3.678; 95% CI, 1.170-11.557) were independent predictors of DMARDs addition. A higher SJC28 and intra-articular GC injection history may be useful predictors of DMARDs addition after the initial MTX monotherapy. We expect that using these predictors will enable an earlier shift to a more aggressive treatment. Key Points ・We performed a retrospective cohort study with the addition of DMARDs as the outcome in patients with RA who were started on MTX monotherapy. ・A higher SJC28 (OR 1.390; 95% CI, 1.036-1.866) and an intra-articular GC injection history (OR 3.678; 95% CI, 1.170-11.557) may be useful predictors for the addition of DMARDs of initiating MTX monotherapy at 6 months. ・The use of such indicators may support an early decision on the addition of DMARDs after the initial MTX monotherapy.

Connective tissue remodelling is differently modulated by tocilizumab versus methotrexate monotherapy in patients with early rheumatoid arthritis: the AMBITION study

ObjectiveAssociations between rheumatoid arthritis (RA) and effect of treatment at the tissue levels are poorly understood. We investigated the scope of released extracellular matrix (ECM) metabolites as a consequence of tissue remodelling in patients treated with methotrexate (MTX) and tocilizumab (TCZ) compared to placebo.MethodsTissue metabolites from 387 RA patients treated with either TCZ (8 mg/kg) or MTX monotherapy (7.5–20 mg/kg) were measured at baseline and 8 weeks sera by validated ELISA assays. The levels of collagen biomarkers (C1M, C2M, C3M and C4M) together with C-reactive protein (CRP) and CRP metabolite (CRPM) were investigated. Baseline levels of biomarkers have been compared with 72 age- and gender-matched healthy controls. Comparison between treatment and response groups were done by ANCOVA, Spearman’s correlation and logistic regression adjusted for age, gender, BMI and disease duration.ResultsC1M and C3M were significantly (P < 0.05) inhibited by TCZ and C3M by MTX (P < 0.01) compared to placebo. C1M and C3M inhibition with TCZ was respectively 23% and 16% greater than that of MTX (P < 0.01 and P < 0.0001). C4M was inhibited by TCZ and MTX, but the effect of TCZ was 22% greater than MTX (P < 0.0001). TCZ and MTX had minimal effect on C2M levels. MTX had no effect on CRP and CRPM, whereas TCZ reduced their levels to 69% and 27% from baseline. Investigated biomarkers revealed a significant (P < 0.05) difference in biomarker profiles of MTX ACR50 treatment responders and non-responders. Change to week 8 in levels of C3M, C4M, CRP and CRPM in MTX patients correlated significantly (rho = 0.41 to 0.18, P < 0.0001 to 0.039) with change in disease activity (DAS28) at weeks 8, 16 and 24, whereas only CRP in TCZ patients (rho = 0.32 to 0.21, P < 0.0001 to 0.01).ConclusionPatients receiving TCZ treatment for 8 weeks had higher suppression of tissue remodelling and inflammatory biomarkers over patients treated with MTX. Measured biomarkers enabled for a discrimination of biomarker profiles of ACR50 treatment responding patients and identification of those who benefit at the early time point. Week 8 change in levels of C3M, C4M, CRP and CRPM significantly predicted clinical response to treatment and correlated with DAS28 at all time points.Trial registrationClinicalTrials.gov, NCT00109408. Date of registration: July 2005. Name of the registry: A Study to Assess the Safety and Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis.

Comparing methotrexate monotherapy with methotrexate plus leflunomide combination therapy in psoriatic arthritis: protocol of a randomized, placebo-controlled, double-blind clinical trial (COMPLETE-PsA)

BackgroundBoth methotrexate (MTX) and leflunomide (LEF) are registered and regularly prescribed as first-line treatments for the use in patients with psoriatic arthritis (PsA) and they are occasionally used in combination. However, evidence about their individual, and especially combined efficacy, in PsA is lacking. The aim of this study is to compare the effectiveness and safety of MTX and LEF combination therapy to MTX monotherapy in patients with PsA.MethodsCOMPLETE-PsA is a randomized, placebo-controlled, double-blind clinical trial. Disease-modifying antirheumatic drug (DMARD)-untreated patients (n = 78) with clinical diagnosis of active (i.e. ≥2 swollen joints) PsA will be randomized 1:1 (stratified for high disease activity, Psoriatic Arthritis Disease Activity Score [PASDAS] ≥ 5.4) to the combination or monotherapy. The intervention group receives MTX 25 mg (oral or subcutaneous) once weekly plus LEF 20 mg daily, and the control group receives the same but with placebo instead of LEF daily. Primary endpoint is between-group difference in PASDAS at 16 weeks, adjusted for baseline PASDAS. Key secondary parameters include between-group comparisons in change in Disease Activity in Psoriatic Arthritis (DAPSA) score, skin score, enthesitis score, dactylitis score, and swollen/tender joint count, as well as the proportion of patients fulfilling minimal disease activity (MDA), American College of Rheumatology (ACR) 20/50/70 response criteria at week 16. Furthermore, safety, function and quality of life (Health Assessment Questionnaire [HAQ], Psoriatic Arthritic Impact of Disease [PSAID], Short Form 12 [SF-12]) will be assessed.DiscussionThis is, to our knowledge, the first randomized, placebo-controlled, double-blind clinical trial assessing the effectiveness of MTX and LEF combination therapy in patients with PsA. The study will provide important information for treatment strategies and treatment recommendations.Trial registrationDutch Trial Register NTR7632 (3 December 2018). CMO NL66544.091.18 (19 November 2018).

Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial

ObjectiveTo examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA).MethodsIn this double‐blind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed.ResultsPatients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed between‐group differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen.ConclusionEtanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at follow‐up. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept.

Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate

ObjectivesMethotrexate is considered to be first-line therapy for rheumatoid arthritis (RA). However, a substantial proportion of treated patients do not achieve the desired goals of therapy. This analysis aimed to...

Assessing joint destruction in the knees of patients with rheumatoid arthritis by using a semi-automated software for magnetic resonance imaging: therapeutic effect of methotrexate plus etanercept compared with methotrexate monotherapy

Objectives: To evaluate the prevention of knee joint destruction and clinical efficacy of methotrexate (MTX) plus etanercept (ETN) compared with MTX monotherapy in patients with rheumatoid arthritis (RA) by using semi-automated software for magnetic resonance imaging (MRI) scan analysis.Materials and methods: This study enrolled patients with active moderate-to-severe RA who displayed an inadequate response to oral MTX at screening. Patients were assigned to receive either MTX plus ETN or MTX monotherapy (≥10 mg/week). The primary endpoint was the quantitative knee cartilage volume using our software developed for MRI scan analysis.Results: A total of 18 female patients were enrolled in this study and allocated to the MTX + ETN group (n = 9) or the MTX monotherapy group (n = 9). At 52 weeks, the quantitative knee cartilage volume was significantly reduced compared with baseline in both groups (MTX plus ETN group: 2.3 ± 2.3 cm3; MTX monotherapy group: 2.4 ± 1.6 cm3); however, the difference was not significant.Conclusion: The semi-automated software for MRI scan analysis can reveal useful and potentially clinically important information about the characteristics of knee joint destruction in patients with RA.

Recent evidence comparing combination of conventional synthetic disease-modifying antirheumatic drugs with biologic disease-modifying antirheumatic drugs in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, disabling inflammatory arthritis often treated with a variety of disease-modifying antirheumatic drugs (DMARDs), whether conventional synthetic DMARDs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), or biological DMARDs (bDMARDs). Most patients with RA are seropositive, have significant disease activity at presentation to the Rheumatologist and may have erosions at the time of diagnosis, all of which are poor prognostic factors. Patients with RA are often initially started on methotrexate (MTX), with addition of other DMARDs, the usual practice in the event of failure of/suboptimal response to MTX monotherapy. Since the recent guidelines by the European League against Rheumatism favor the use of bDMARDs over the combination of csDMARDs following the failure of MTX monotherapy in patients with such poor prognostic factors, we decided to review the recent literature comparing combination csDMARDs with bDMARDs. Long-term follow-up of landmark trials such as the Behandel-Strategieeen study (10 years) and NEO-RACo study (5 years) as well as other trials supports similar efficacy of both strategies in terms of clinical and functional outcomes. Whereas some studies have shown a minor but statistically significant progression of radiographic damage in those receiving combination of csDMARDs versus those on bDMARDs, others have not, further confirmed in a recent meta-analysis. Thus, keeping in mind, the similar efficacy and better cost-effectiveness of combination of csDMARDs, this should be the preferred strategy following failure of MTX monotherapy. bDMARDs should be reserved when combination csDMARDs fail, especially in an Indian scenario where most patients are poor and a majority of healthcare is not government-sponsored.

Induction maintenance with tumour necrosis factor-inhibitor combination therapy with discontinuation versus methotrexate monotherapy in early rheumatoid arthritis: a systematic review and meta-analysis of efficacy in randomised controlled trials

ObjectiveTo determine whether an induction-maintenance strategy of combined therapy (methotrexate (MTX)+tumour necrosis factor (TNF) inhibitor (TNFi)) followed by withdrawal of TNFi could yield better long-term results than a strategy with...

Tofacitinib versus Methotrexate in Rheumatoid Arthritis

BackgroundMethotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate.MethodsWe randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (≥70% reduction in the number of both tender and swollen joints and ≥70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician).ResultsMean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels.ConclusionsIn patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start ClinicalTrials.gov number, NCT01039688.)

AB0327 Progression of Atherosclerosis in Premenopausal Rheumatoid Arthritis Patients Treated with Methotrexate – A Five Year Follow up Study

BackgroundLife expectancy in rheumatoid arthritis (RA) patients is reduced by 3-10 years mainly due to cardiovascular diseases. In the core study, we found that selected normotensive, non-diabetic, premenopausal RA patients...

AB0459 Audit of Methotrexate and Pulmonary Function Tests

BackgroundMethotrexate pneumonitis (MTX-P) is most frequently seen within the first year of treatment1 and is best avoided in established cases of Interstitial Lung disease (ILD). BSR recommends that if pre-treatment...