Methotrexate Combination Therapy Research Articles

Early prediction of treatment response in rheumatoid arthritis by quantitative macrophage PET

ObjectiveTo determine whether macrophage positron emission tomography (PET)/computed tomography (CT) imaging using (R)-[11C]PK11195 at 0 and 2 weeks is associated with clinical response at 13 weeks in patients with early...

Na-AIP-1 secreted by human hookworms suppresses collagen-induced arthritis.

Proteins from helminths have been posed as new immunomodulatory agents with exciting potential in the treatment of immune-mediated diseases including rheumatoid arthritis (RA). In this study we assess the effects of a helminthic excretory/secretory (ES) protein Na-AIP-1 as monotherapy and in combination with methotrexate (MTX) in the well-described collagen-induced arthritis (CIA) model of RA. CIA was induced in DBA/1J mice which were treated after the onset of arthritis with Na-AIP-1 monotherapy, MTX or Na-AIP-1 + MTX. The clinical scores for weight, arthritis and paw width were recorded along with joint histology as outcome measures. For the clinical parameters of weight, paw score and paw width, none of the Na-AIP-1 monotherapy, MTX therapy or Na-AIP-1 + MTX combination therapy groups displayed any significant difference when compared to the arthritis control. However, a significant reduction in histological score was identified after both monotherapy (Na-AIP-1: 0.83 ± 0.24 vs Arthritis control: 5.58 ± 1.49, p = 0.0277) and combination therapy (Na-AIP-1 + MTX: 0.55 ± 0.28 vs Arthritis control: 5.58 ± 1.49, p = 0.0233) when compared to arthritis control. Furthermore, Na-AIP-1 as both monotherapy (Na-AIP-1: 0.83 ± 0.24 vs MTX: 5.73 ± 1.82 p = 0.0261) and combination therapy (Na-AIP-1 + MTX: 0.55 ± 0.28 vs MTX: 5.73 ± 1.82, p = 0.0221) also significantly reduced histological score when compared to MTX monotherapy. Na-AIP-1 significantly reduced joint pathology in CIA. The hookworm protein Na-AIP-1 seems to be effective in the treatment of RA as monotherapy and when dosed together with MTX, constituting a potential new candidate for drug development. Research should focus on elucidating the mechanism of Na-AIP-1 action as a means to identify novel targets for therapeutics and to further our current understanding of immunobiology in RA.

Clinical Characteristics and Efficacy of Adalimumab and Low-Dose Methotrexate Combination Therapy in Patients With Vogt-Koyanagi-Harada Disease.

This retrospective study investigated the clinical characteristics and efficacy of adalimumab and low-dose methotrexate combination therapy in patients with Vogt–Koyanagi–Harada disease who were treated at Hiroshima University from February 2012 to May 2021. The patients' demographics, clinical features at administration of immunosuppressive therapy, steroid-sparing immunosuppressive therapy, side effects, and relapses were recorded. The efficacies of steroid-sparing immunosuppressive therapy (methotrexate, cyclosporine A, adalimumab, and adalimumab and methotrexate combination therapy) were analyzed. Among 62 patients, the median age at diagnosis was 47 years and the median duration of uveitis was 51 months. Systemic corticosteroid therapy was administered to 93.5% of patients (n = 58). Thirty-four patients (54.8%) were treated with steroid-sparing immunosuppressive therapy. Methotrexate and cyclosporine A were administered to 12 and 22 patients, respectively; relapse occurred in 50.0% and 22.7% of the patients, respectively. Discontinuation of cyclosporine A was required in 63.6% of patients because of side effects. Adalimumab was administered to 14 patients. Recurrence occurred in 11 patients, requiring methotrexate concomitantly. The mean dose of methotrexate at inflammatory quiescence after side effect-related dose decrease was 8.0 mg/week (0.13 mg/kg). The median duration of combination therapy without recurrence was 20 months. There were no serious adverse events during adalimumab therapy. A high relapse rate was observed in patients receiving methotrexate; a high rate of side effects requiring discontinuation was observed in patients receiving Cyclosporine A. Patients with late-stage Vogt–Koyanagi–Harada disease may achieve better control with adalimumab and methotrexate combination therapy.

Experts document on methotrexate use in combined therapy with biological or targeted synthetic disease modifying drugs in patients with rheumatoid arthritis

ObjectiveWe aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). MethodsEleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted ‘yes’ (yes/no). ResultsThe systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients’ risk management. ConclusionsThis document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs.

Clinical manifestations of gastrointestinal tract changes in children with juvenile idiopathic arthritis

Summary. Juvenile idiopathic arthritis remains one of the most common chronic inflammatory rheumatic diseases of childhood. A significant proportion of patients experience nausea, vomiting, abdominal pain and loss of appetite with methotrexate therapy, which can significantly complicate the course of the disease. The aim was to study the clinical and anamnestic signs of liver disorders in children, depending on the manifestations of juvenile idiopathic arthritis. Materials and methods of research. The presence of gastrointestinal complaints, namely abdominal pain, loss of appetite, nausea and vomiting in 104 children with juvenile idiopathic arthritis who were treated at the State Institution "Institute of Child and Adolescent Health of the National Academy of Medical Sciences of Ukraine" was analyzed. Results. According to the results of the study, children with juvenile idiopathic arthritis had gastrointestinal complaints in 47.12%. We find out that the majority of children had gastrointestinal complains at the age of 10–13 years (55.36%, p ˂ 0.001), and at the onset of the disease after 15 years (100%, p ˂ 0.01). Young children often complained of abdominal pain and vomiting, older children complained of loss of appetite and persistent nausea, regardless of the variant, activity, duration of arthritis and the presence of methotrexate in complex therapy. It was also found that appearance of gastrointestinal complaints were observed more often at a dose of methotrexate less than 10 mg / m2 / body surface (p ˂ 0.05). Conclusions. 1. We find out that in 47.12% children with juvenile idiopathic arthritis had gastrointestinal complaints, aged 10–13 years (55.36%; p ˂ 0.001). The most amounts of complaints were common for patients older than 15 years old (p ˂ 0.01). 2. The nature of the complaints varied and depended mainly on the age of the patients. Younger children had abdominal pain and vomiting simultaneously older children had decreased appetite and nausea. The presence of complaints did not depend on the variant, activity and duration of the juvenile idiopathic arthritis. 3. According to our study complaints were not due to the presence of methotrexate in combination therapy. Children complained much more often if methotrexate dose was less than 10 mg / m2 than in the case of higher doses (p ˂ 0.05).

The Effect of Systemic Methotrexate and Cyclosporine Combination Therapy inPsoriasis Vulgaris Patients in Bandung, Indonesia

Background: Methotrexate (MTX) and cyclosporine have been used as effective systemic mono-therapy for psoriasis. Several factors are considered to switch monotherapy to combination therapy because monotherapy is no longer effective and has higher side effects. Hence,clinicians have avoided systemic therapy combinations due to its toxicity. However, some studies showed that this combination therapy could be usedeffectively for psoriasis patients. Purpose: This study aimed to analyze the efficacy and adverse effects of systemic MTX and cyclosporine combination therapy in Indonesian psoriasis vulgaris patients. Methods: The retrospective study assessed the effectiveness of 3 monthsmono-therapyand combination therapy of systemic MTX and cyclosporine in psoriasisvulgaris patients from 2016–2017 in Dermatology Clinic, Dr. Hasan Sadikin Hospital, Bandung, West Java, Indonesia. Result: Psoriasis area and severity index (PASI) score 90 were achieved in the group MTX (50%) and cyclosporine group (50%), while none in the combination group.However, eight patients (50%) in group MTX and cyclosporine reached the primary endpoint of PASI 50. One patient in cyclosporine group had adverse effects on kidney profiles. Nonetheless, other patients had no biochemical changes. But, there was no significant difference in the change of PASI between each group (p=0.102). Conclusion: We propose that combination therapy of MTX and cyclosporine is relatively safe and efficacious in treating Indonesian psoriasis vulgaris patients. This combination treatment isas effective as MTX or cyclosporinemono-therapy.

Sustained Remission in Rheumatoid Arthritis: Time to Withdraw Treatment?

With increasing numbers of patients with rheumatoid arthritis achieving sustained remission, medication withdrawal is an important consideration to reduce polypharmacy and associated adverse events. An article from the journal Arthritis & Rheumatology (1) explores the treatment withdrawal options for patients on etanercept and methotrexate combination therapies and suggests methotrexate withdrawal has the least impact on disease worsening. There are limitations in the study, including the use of only one disease activity score and no assessment of radiographic progression, but, overall, the article provides a good framework for future studies on treatment withdrawal options and the possibility of medication reduction for patients.

Effects of Combination Therapy of Methotrexate with Sulfasalazine and Hydroxychloroquine: Comparative Clinical Trial

Aims: To study the role of two combination therapies in the treatment of rheumatoid arthritis. Study Design: This an open-label, randomized 180-days clinical trial.
 Place and Duration of Study: This study was conducted in the Department of Pharmacology and Therapeutics, BMSI and Medical unit ward 6.
 Methodology: Eighty-nine patients were enrolled (69 women, 20 men; age range 28-62 years). A and B were the groups assigned to the patients. MTX 7.5-20 mg/ week orally and SSZ 10-20 mg / day orally as maximally tolerated were prescribed to the 55 patients of group A. MTX 7.5-20 mg/ week orally and HCQ 200 mg twice daily were prescribed to the 54 patients of group B..
 Results: When we compared group A with group B, group A showed major progress in mean swollen joint count (1.9 ± 0.97) as compared to group B (2.7 ± 1.78). Group B showed major progress in mean physician’s global assessment (2.7 ± 0.92) as compared to group A (3.8 ± 1.22). For that reason, our study showed that patients receiving both the combinations responded equally in terms of efficacy but the combination of MTX and HCQ is better tolerated than the combination of MTX and SSZ.
 Conclusion: Both combinations of MTX & SSZ and MTX & HCQ were equally effective but the combination of MTX & HCQ was superior in terms of tolerability than the combination of MTX and SSZ.

Efficacy of combination therapy of steroid and methotrexate for refractory pemphigus

AbstractThe first line of treatment for pemphigus is systemic corticosteroids. When steroids alone do not result in remission, additional immunosuppressants are recommended. Twenty‐two patients with pemphigus vulugris were treated with steroids and other immunomodulators. However, they were refractory, and hence, methotrexate (MTX) was administered. The efficacy of MTX was assessed for 16 patients who were able to continue MTX therapy for 1 year. Steroid dose reduction was possible in 11 patients. One patient with severe infections had diabetes and was elderly. Our results suggested that MTX was useful as a steroid‐sparing agent in treating recalcitrant pemphigus, when an initial immunosuppressant treatment had failed. However, adverse effects should be closely monitored.

POS1341 TOCILIZUMAB FOR THE TREATMENT OF IMMUNE-RELATED ADVERSE EVENTS TO IMMUNE CHECKPOINT INHIBITORS: A CASE SERIES

Background:Immune checkpoint inhibitors (ICI) are pharmacological agents effectively used in the treatment of several malignant tumors. The hyperactivation of the immune system induced by ICI may trigger an inflammatory involvement of healthy tissues, a phenomenon referred to as immune-related adverse event (irAE). No clinical trials are available to guide the management of irAEs. Observational data suggest tocilizumab might be effective in severe cases of irAEs, but data are scant. The possibility of continuing ICI treatment despite the development of irAE and the subsequent initiation of tocilizumab has never been evaluated.Objectives:To evaluate the efficacy and safety of tocilizumab, as monotherapy or alongside the continuation of ICI treatment, in the management of irAEs.Methods:We retrospectively identified patients who developed irAEs and were referred to our specialized Clinic between May 2018 and December 2020. Among these patients, we identified those who had been treated with tocilizumab and collected information about their oncologic history and outcome, ICI therapy and irAEs.Results:Thirty-nine patients were referred to our outpatient Clinic following the development of irAEs. Five of them were treated with tocilizumab. Disease and demographic features are reported in Table 1. At irAEs onset all patients were treated with glucocorticoids. A steroid-sparing agent was started to permit an adequate prednisone tapering without the irAE relapsing. Before tocilizumab start, two patients were treated with methotrexate monotherapy, one with anakinra monotherapy, and one with methotrexate and anakinra combination therapy. A significant therapeutic effect was confirmed in all patients and no significant adverse reactions were reported. ICI therapy was permanently discontinued in two patients. In the other three cases, cancer immunotherapy was safely continued alongside tocilizumab without further irAEs occurring. Only one patient experienced tumor progression two years after ICI suspension and subsequently died despite the improvement of his myocardial inflammatory involvement.Conclusion:In our cohort, tocilizumab proved to be an effective and safe therapy for the management of irAEs.Our case series also supports the possibility of maintaining ICI while introducing tocilizumab for irAE treatment. This combined approach might represent a suitable therapeutic option to guarantee a significant anti-inflammatory activity without losing the oncologic response.

Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission.

ObjectivePatients with rheumatoid arthritis (RA) in whom remission is achieved following combination therapy with methotrexate plus etanercept face an ongoing medication burden. This study was undertaken to investigate whether sustained remission achieved on combination therapy can be maintained with either methotrexate or etanercept monotherapy, as assessed following discontinuation of one or the other medication from the combination.MethodsOf the 371 adult patients with RA who received combination therapy with methotrexate plus etanercept, remission (defined as a Simplified Disease Activity Index [SDAI] score of ≤3.3) was sustained in 253 patients through a 24‐week open‐label period. These 253 patients then entered a 48‐week, double‐blind period and were randomized to receive either 1) methotrexate monotherapy (n = 101), 2) etanercept monotherapy (n = 101), or 3) methotrexate plus etanercept combination therapy (n = 51). Patients who subsequently experienced disease‐worsening received rescue therapy with the combination regimen at the same dosages as used in the initial run‐in period. The primary end point was the proportion of patients in whom SDAI‐defined remission was maintained without disease‐worsening at week 48 in the etanercept monotherapy group as compared to the methotrexate monotherapy group. Secondary end points included time to disease‐worsening, and the proportion of patients in whom SDAI‐defined remission was recaptured after initiation of rescue therapy.ResultsBaseline demographic and clinical characteristics of the RA patients were similar across the treatment groups. At week 48, SDAI‐defined remission was maintained in significantly more patients in the etanercept monotherapy group than in the methotrexate monotherapy group (49.5% versus 28.7%; P = 0.004). Moreover, as a secondary end point, sustained SDAI‐defined remission was achieved in significantly more patients who received combination therapy than in those who received methotrexate monotherapy (52.9% versus 28.7%; P = 0.006). Time to disease‐worsening was shorter in those who received methotrexate monotherapy than in those who received etanercept monotherapy or those who received combination therapy (each P < 0.001 versus methotrexate monotherapy). Among the patients who received rescue therapy, SDAI‐defined remission was recaptured in 70–80% in each treatment group. No new safety signals were reported.ConclusionThe efficacy of etanercept monotherapy was superior to that of methotrexate monotherapy and similar to that of combination therapy in maintaining remission in patients with RA. SDAI‐defined remission was recaptured in most of the patients who were given rescue therapy. These data could inform decision‐making when withdrawal of therapy is being considered to reduce treatment burden in patients with well‐controlled RA.

Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients.

AimTo identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients.Materials and methodsDNA from baseline peripheral blood mononuclear cells was extracted from 72 RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy over the first 3 months.ResultsBaseline DMPs associated with response were identified; including hits previously described in RA. Additionally, 1309 DMR regions were observed. However, none of these findings were genome-wide significant. Likewise, no specific pathways were related to response, nor could we replicate associations with previously identified DMPs.ConclusionNo baseline genome-wide significant differences were identified as biomarker for MTX (combination) therapy response; hence meta-analyses are required.

Low-Dose Methotrexate Use in Idiopathic Granulomatous Mastitis: An Alternative Treatment Method

Background: Idiopathic granulomatous mastitis (IGM) is a rare, recurrent and progressive breast disease with an unknown etiology. Patients with IGM will probably face stressful, time-consuming treatment procedures with side effects due to medications. There are different treatment modalities in clinical use including medical and surgical interventions. Objective: The aim of this study was to present the results of using the combination therapy of low-dose methotrexate (MTX) and steroid in IGM. Methods: Seventeen patients diagnosed with IGM and treated with MTX were included into the study. Low-dose MTX at 5 mg/week and 8 mg/day prednisone were given for 2–3 months. Results: After 2–3 months of treatment, 10 patients exhibited (58.5%) complete, 3 patients (17.6%) partial recovery, and no response to the treatment process was observed in 4 patients (23.5%). No side effects of MTX and recurrent events were noted in any of the patients. Conclusion: Low-dose MTX and prednisone treatment for IGM patients, who did not respond to steroids alone, should be considered as an alternative treatment method instead of surgical intervention.

Complex Machine-Learning Algorithms and Multivariable Logistic Regression on Par in the Prediction of Insufficient Clinical Response to Methotrexate in Rheumatoid Arthritis.

The goals of this study were to examine whether machine-learning algorithms outperform multivariable logistic regression in the prediction of insufficient response to methotrexate (MTX); secondly, to examine which features are essential for correct prediction; and finally, to investigate whether the best performing model specifically identifies insufficient responders to MTX (combination) therapy. The prediction of insufficient response (3-month Disease Activity Score 28-Erythrocyte-sedimentation rate (DAS28-ESR) > 3.2) was assessed using logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting (XGBoost). The baseline features of 355 rheumatoid arthritis (RA) patients from the “treatment in the Rotterdam Early Arthritis CoHort” (tREACH) and the U-Act-Early trial were combined for analyses. The model performances were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves, 95% confidence intervals (95% CI), and sensitivity and specificity. Finally, the best performing model following feature selection was tested on 101 RA patients starting tocilizumab (TCZ)-monotherapy. Logistic regression (AUC = 0.77 95% CI: 0.68–0.86) performed as well as LASSO (AUC = 0.76, 95% CI: 0.67–0.85), random forest (AUC = 0.71, 95% CI: 0.61 = 0.81), and XGBoost (AUC = 0.70, 95% CI: 0.61–0.81), yet logistic regression reached the highest sensitivity (81%). The most important features were baseline DAS28 (components). For all algorithms, models with six features performed similarly to those with 16. When applied to the TCZ-monotherapy group, logistic regression’s sensitivity significantly dropped from 83% to 69% (p = 0.03). In the current dataset, logistic regression performed equally well compared to machine-learning algorithms in the prediction of insufficient response to MTX. Models could be reduced to six features, which are more conducive for clinical implementation. Interestingly, the prediction model was specific to MTX (combination) therapy response.

Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

BackgroundRemission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease.MethodsA multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit.ResultsBy intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients.ConclusionsEarly combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

15111 Incidence of hepatic fibrosis in psoriasis patients receiving methotrexate and acitretin combination therapy in a tertiary-care hospital in Thailand

Background: Methotrexate and acitretin are both effective in psoriasis. There has been limited reports of concomitant therapy due to a theoretical concern of potential hepatotoxicity. However, a comparative study demonstrated that the combination therapy exhibited higher effectiveness in remitting psoriatic lesion, and less fibrogenic effect on liver compared with monotherapies.

TNF-Like Weak Inducer of Apoptosis Promotes Angiogenesis, Thereby Exacerbating Cutaneous Psoriatic Disease

TNF-Like Weak Inducer of Apoptosis Promotes Angiogenesis, Thereby Exacerbating Cutaneous Psoriatic Disease

Experts document on methotrexate use in combined therapy with biological or targeted synthetic disease modifying drugs in patients with rheumatoid arthritis.

We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA). Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs. A systematic review was conducted to answer the questions. Inclusion and exclusion criteria were established as well as the search strategies (Medline, Embase and the Cochrane Library were searched up to January 2019). Two reviewers selected the articles and collected data. Simultaneously, EULAR and ACR meeting abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with a Delphi. Agreement was established if at least 80% of the experts voted 'yes' (yes/no). The systematic review retrieved 513 citations of which 61 were finally included. A total of 10 recommendations were generated, voted and accepted. The level of agreement was very high in all of them and it was achieved in the first Delphi round. Final recommendations cover aspects such as the optimal MTX dosage, tapering strategy or patients' risk management. This document is intended to help clinicians solve usual clinical questions and facilitate decision making when treating RA patients with MTX in combination with bDMARDs or tsDMARDs.

Effects of Combination Therapy of Methotrexate with Leflunomide &amp; Hydroxychloroquine: Comparative Clinical Trial

Aims: To study the role of combination therapies in the treatment of rheumatoid arthritis.&#x0D; Study Design: This an open-label, randomized 180-days clinical trial.&#x0D; Place and Duration of Study: This study was conducted in the Department of Pharmacology and Therapeutics, BMSI and Medical unit ward 6, after approval of JPMC ethical committee, between March 2013 and May 2014.&#x0D; Methodology: We included 90 patients (69 women, 21 men; age range 28-62 years) which were divided into two groups, A and B. 44 patients of group A received methotrexate (MTX) 7.5-20 mg/ week orally and Leflunomide (LEF) 10-20 mg/ day QD orally as maximally tolerated. 46 patients of group B were given MTX 7.5-20 mg/ week orally and Hydroxychloroquine (HCQ) 200 mg twice daily orally as maximally tolerated.&#x0D; Results: Comparing the combination of group A with group B, group A showed highly significant improvement in mean patient’s global assessment (1.4 ± 0.66) and mean pain (1.3 ± 1.11) as compared to group B (2.4 ± 1.14, 2.2 ± 1.49). The drugs of group B showed significant improvement in mean physician’s global assessment (1.7 ± 0.92) and mean morning stiffness (49.2 ± 10.59) as compared to group A (2.8 ± 0.97, 54.4 ± 10.14). Combination treatment of group B showed significantly lower adverse effects (4.3%) as compared to group A (11.4%). Statistical analysis revealed that patients receiving both the combinations responded equally in terms of effects but group B showed significantly better in terms of adverse effects.&#x0D; Conclusion: Both combinations of MTX &amp; LEF and MTX &amp; HCQ were well tolerated but the efficacy of MTX and HCQ was significantly superior in terms of adverse effects to the combination of MTX and LEF.

Predictors of disease flare after discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab.

To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI]≤10) for≥12weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score>10 or intervention with rescue treatments for any reason even if the CDAI score was≤10. The impact of baseline characteristics on disease flare at week 64 (52weeks after methotrexate discontinuation) was assessed with logistic regression models. Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6-81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4weeks, or subcutaneously every 2weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80-115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72-83.80) were independent predictors of disease flare. Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. jRCTs041180071, UMIN000021247.