Methotrexate Combination Therapy Research Articles

P0831 Improving efficiency in early phase clinical trials for inflammatory bowel disease through use of external control arms

Abstract Background Although randomised controlled trials (RCTs) are the gold standard for evaluating medical interventions, enrolling enough patients in early-phase trials in inflammatory bowel disease (IBD) to provide sufficient efficacy and safety information prior to confirmatory trials can be difficult.1,2 In a landscape where combination therapies frequently require monotherapy controls and where placebo responses are well-understood, improving trials with external control (EC) data may enhance phase 1-2 trial designs. Methods Current possibilities of using EC data in IBD trials from both methodological and statistical perspectives were explored. Methods of utilising EC data were reviewed, including results of a systematic review of immune-mediated inflammatory disease (IMID) trials that utilised external control arms (ECAs)3, and an example of Bayesian analyses integrating EC data used in an RCT comparing combination treatment to monotherapy benchmarks.4 How EC data fits into the intersection between operational efficiency and good clinical practice was examined. Results Multiple simultaneous ongoing IBD studies, strict objective clinical endpoints (eg, endoscopic remission), and declining enrolment rates have led to increasing difficulty in meeting IBD trial recruitment goals. The prevalence of add-on and combination therapies suggests that trials may need multiple control arms to fully explore efficacy and safety of investigational treatments. Using EC data can increase power and allow for exploratory comparisons across multiple controls in modest-sized trials. Techniques and considerations on how to ethically and effectively use EC data to improve clinical trials, however, are not as thoroughly discussed in the literature. Systematic review of controlled trial databases for IMID studies utilising ECAs resulted in 18 IBD studies that met the search criteria, over three-fourths of which did not control for baseline characteristics between external and trial data (Table 1).1 Furthermore, half of the quality assessment items during evaluation could not be assigned a rating due to insufficient methodology details provided in publications. Conclusion Multiple factors have led to increasing difficulty for IBD trials reaching their recruitment goals. In early phase trials particularly, the use of EC data may allow studies to increase power and decision-making information. More comprehensive reporting, as well as the creation of a validated instrument for appraising ECA methodology, are required to thoroughly understand and evaluate EC data use in studies. References 1Harris MF, Wichary J, Zadnik M, Reinisch W. Competition for clinical trials in inflammatory bowel diseases. Gastroenterology. 2019;157(6):1457-1461. doi:10.1053/j.gastro.2019.08.020 2Ma C, Solitano V, Danese S, Jairath V. The future of clinical trials in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2024;Jul 16:S1542-3565(24)00635-9. doi:10.1016/j.cgh.2024.06.036 3 ayadi A, Edge R, Parker CE, Macdonald JK, Neustifter B, Chang J, et al. Use of external control arms in immune-mediated inflammatory diseases: a systematic review. BMJ Open. 2023;13(12):e076677. doi:10.1136/bmjopen-2023-076677 4Colombel JF, Ungaro RC, Sands BE, Siegel CA, Wolf DC, Valentine JF, et al. Vedolizumab, adalimumab, and methotrexate combination therapy in Crohn’s disease (EXPLORER). Clin Gastroenterol Hepatol. 2024;22(7):1487-1496. doi:10.1016/j.cgh.2023.09.010

P0897 Association of HLA Genotypes with Anti-Drug Antibody Development in Taiwanese Inflammatory Bowel Disease Patients Undergoing Biologic Therapies

Abstract Background Anti-drug antibodies (ADAs) are a primary factor in the loss of response to infliximab and other adverse drug reactions. The genetic variant HLA-DQA1*05 has been associated with infliximab antibody development in Crohn’s disease (CD) among European populations. This study aims to assess the relationship between HLA genotypes and ADA formation in non-European inflammatory bowel disease (IBD) patients receiving anti-tumor necrosis factor (TNF), anti-integrin, or anti-IL-12/23 therapies. Methods This prospective cohort study enrolled patients with IBD receiving anti-TNF, anti-integrin, or anti-IL-12/23 therapy between January 2022 and March 2024. NGS-based HLA genotyping was performed for all participants. The occurrence of ADAs was assessed, and the frequencies of specific HLA alleles were compared between patients who developed ADAs and those who did not. Additionally, HLA allele frequencies in ADA-positive patients were analyzed against the general population in Taiwan. Results A total of 95 patients with IBD were included in the study, along with HLA genotype data from 1,097 control individuals obtained from the Taiwan Biobank. Among the IBD patients, 58 received anti-TNF therapy, 27 underwent anti-integrin therapy, and 10 were treated with anti-IL-12/23 therapy. According to the reimbursement criteria in Taiwan, all patients have to be treated with conventional therapy and when with inadequate response or with adverse effects, then biologics would be reimbursed. Therefore, all the 95 patients were under the biologics and immunosuppressive agents (either thiopurine or methotrexate) combination therapy. No ADA development was observed in patients treated with anti-integrin or anti-IL-12/23 therapies. However, among the 58 patients treated with anti-TNF therapy (38 with infliximab and 20 with adalimumab), 21 developed ADAs (18 infliximab-related and 3 adalimumab-related). A comparison of patients with and without ADAs revealed a significant association between the HLA-C*03:04:01 allele and ADA development (33.3% vs. 10.8%, p=0.035), whereas the HLA-DQA1*05 allele showed no association (52.3% vs. 51.4%, p=0.940). The frequency of the HLA-C*03:04:01 allele was comparable between IBD patients and the broader Taiwanese population (16.8% vs. 11.2%, p=0.0915). Conclusion This study demonstrated that the different HLA locus associated with ADA development among different ethnics. While HLA-DQA1*05 was found in European cohort, our data showed that HLA-C*03:04:01 was significantly associated with an increased risk of anti-TNF antibodies formation in Taiwanese IBD patients.

Clinical Prediction Score of 1-Year Sustained Remission to Methotrexate Combination Therapy in Patients with Early Rheumatoid Arthritis

Objective: To develop a prediction stratification score for the prediction of sustained remission (SR) to methotrexate (MTX) therapy in patients with early rheumatoid arthritis (ERA). Materials and Methods: Prognostic research with clinical prediction score was conducted. All patients with ERA who experienced moderate to high disease activity at a tertiary hospital were included. Multivariable logistic regression models were used to assess each variable predictor. Logistic coefficients of each predictor were used for generating scores. Predictive performance was internally validated using bootstrapping techniques. Results: One hundred seventy-five patients, of which 93 had SR, were included. The prediction score had four final predictors, age less than 65 years (0, 2), initial health assessment questionnaires less than 1 (0, 3), baseline disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) (0, 1), and DAS28-ESR at three months less than 3.2 (0, 5) were included in the logistic model. The positive predictive value for the high-risk score, which was greater than 3.5, was 87 (95% CI 76.7 to 93.9) results used in the model as a clinical predictor of MTX response. The SR score had a good predictive performance (AUROC 0.85, 95% CI 0.80 to 0.90). Conclusion: The SR score demonstrated good performance and discrimination for predicting SR to MTX combination therapy in patients with ERA for a safe long term follow up using simplified parameters in a clinical setting.

Methotrexate inhibits glucocorticoids-induced osteoclastogenesis via activating IFN-γR/STAT1 pathway in the treatment of rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA) is a chronic autoimmune disease characterised by the synovitis and bone erosion. The combination therapy of glucocorticoids (GCs) and methotrexate (MTX) is recommended in early RA management,...

Efficacy of Methotrexate and Anti-TNF Combination Therapy in Adults with Refractory Crohn's Disease.

Biological medications have played a significant role in maintenance therapy for Crohn's disease (CD), but some cases become refractory to these agents. Methotrexate (MTX) appears to be a cost-effective and readily available drug for enhancing the effectiveness of maintenance therapy when used in combination with anti-tumor necrosis factor (anti-TNF) therapy in such cases. However, its effectiveness is still to be established. We aimed to assess the efficacy of MTX and anti-TNF combination therapy in patients with refractory CD. A retrospective cohort study was conducted on adult patients with CD who were refractory to anti-TNF therapy and were initiated on weekly intravenous MTX in addition to the anti-TNF therapy. These patients were then followed up for over a year. The primary outcome measured was the clinical response to treatment, based on the Harvey-Bradshaw Index. The secondary outcomes included assessing the adverse events and complications of MTX therapy. Of 70 patients, 44 were included in the final analysis. Among them, 30 patients (68.2%) achieved complete remission, four patients (9.1%) had a partial clinical response, and 10 patients (22.7%) required surgery. The adverse events and complications of MTX therapy were mild and infrequent (9.1%). None of the demographic or clinical factors were significantly associated with response to treatment (P>0.05). Combining MTX with anti-TNF therapy appears to be an effective and safe treatment for patients with Crohn's disease, particularly those with severe disease who are less responsive to monotherapy. However, further studies are needed to confirm these findings.

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.

Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial

BackgroundEtanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial.Methods92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week.Results32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4–10), median 10 months (7–16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6–9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group.ConclusionsEscalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety.Trial registrationDutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585.

Risks of malignant lymphoma in rheumatoid arthritis patients receiving methotrexate-alone and in combination therapy compared with the general population: A study based on a Japanese medical claims database.

The risk of malignancy in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) and biological disease-modifying antirheumatic drug (bDMARD) combination therapy is unknown. This study aimed to clarify the incidence of malignancy and the recommended monitoring period in patients receiving this combination therapy. A retrospective, observational study based on a large Japanese medical claims database was conducted between April 2013 and February 2020. Patients with RA were classified into MTX-alone and combination therapy groups, and the standardized incidence rates (SIR) of malignancy were calculated. The time of onset of malignancy in both groups was calculated. In total, 2,052 patients received MTX-alone and 782 received combination therapy. The incidence of malignant lymphoma was significantly higher with MTX-alone therapy (SIR: 6.09, 95% confidence interval (CI): 1.58-10.61) and combination therapy (SIR: 20.86, 95% CI: 8.53-33.19) than in the general Japanese population. Furthermore, the combination therapy had a significantly higher risk of malignant lymphoma than the MTX-alone therapy (adjusted odds ratio: 4.27, 95% CI: 1.64-11.12). The median time from MTX prescription to the onset of malignant lymphoma was 3.58 years (interquartile range (IQR): 2.00-5.34 years) for MTX-alone and 3.42 years (IQR: 1.25-4.92 years) for combination therapy. The incidence of malignant lymphoma in the combination therapy group was extensively higher than that in the general Japanese population. Special attention is required for early symptoms of malignant lymphoma, particularly in the 3rd - 4th year after initiating MTX therapy.

The use of methotrexate in rheumatoid arthritis. Recommendations of the All-Russian public organization “Association of Rheumatologists of Russia”

Rheumatoid arthritis (RA) is the most frequent immunoinflammatory (autoimmune) rheumatic disease characterized by chronic erosive arthritis and systemic damage to internal organs. The data obtained in the course of basic research on deciphering the mechanisms of action of methotrexate (MT) and the materials of numerous randomized placebocontrolled trials, observational studies and national registries have strengthened the position of MT as the “gold standard” of RA pharmacotherapy and a key component of the “Treatment to Target” strategy. This was the basis for the development of new recommendations of the Association of Rheumatologists of Russia (ARR) concerning the use of MT in RA, according to which MT is considered as the drug of “choice” for induction and maintenance of remission in patients with early and advanced RA, including those who need combination therapy of MT with glucocorticoids, standard Disease-Modifying Antirheumatic Drugs (DMARDs), biologics and targeted synthetic DMARDs. Special attention is paid to the safety of MT therapy and the impact of MT on comorbid pathology associated with cardiovascular complications and interstitial lung disease. Implementation of the ARR recommendations into clinical practice will reduce the risk of disability and improve life prognosis in patients with RA.

A Combination Therapy of Methotrexate and Xianling Gubao Capsule for Female Patients with Moderate to Severe Active Rheumatoid Arthritis and its Impact on Ovarian Function

Rheumatoid arthritis is a common immune disease with early symptoms of joint swelling, morning stiffness, pain, and swelling. It could develop into a joint deformity as the disease progresses, resulting in the loss of normal joint function and seriously affecting the patient’s quality of life. Methotrexate is the “anchor drug” for rheumatoid arthritis treatment, which has an immunosuppressive effect and could effectively prevent the abnormal activation of B cells in vivo, inhibit the abnormal generation of cytokines, and relieve related symptoms. However, in some cases, methotrexate alone is not ideal and often needs to be combined with other drugs like xianlinggubao capsules. This study has provided an experimental basis for the combined efficacy of methotrexate and xianlinggubao capsules for female patients with moderate to severe rheumatoid arthritis and their impact on ovarian function.

Tripterygium wilfordii Hook F combination therapy with methotrexate for rheumatoid arthritis: An updated meta-analysis.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory arthropathy. Tripterygium wilfordii Hook F (TwHF) is common herbal medicine for the treatment of RA in China. However, many important issues, such as efficacy, safety and optimal doses of the combination therapy of TwHF and Methotrexate (MTX) for RA remain to be evaluated. This study aims to evaluate the efficacy and safety of combination therapy of TwHF and MTX for RA by meta-analysis of randomized clinical trials (RCTs). Relevant literature was searched from English (PubMed, Web of Science, EMBASE, and Cochrane library) and Chinese databases (WanFang, VIP, CNKI) until December 2021. Response rates and rates of adverse events (AEs) were independently extracted and analyzed. Fourteen randomized controlled trials (RCTs) were included with a total of 1446 patients, which included eight new RCTs with a total of 803 new patients when compared with the previous meta-analysis (Wang et al., 2017). Compared to MTX monotherapy, TwHF+MTX was revealed a higher effective rate (RR=1.15, 95% CI: 1.10, 1.21), partial remission rate (RR=1.27, 95% CI: 1.15, 1.40) and remission rate (RR=1.31, 95% CI: 1.11, 1.55). The addition of TwHF benefited the clinical symptoms (such as tender joint count) and most laboratory indexes (such as the tumor necrosis factor-α). According to the subgroup analyses, the efficacy of the TwHF+MTX seems to be positively associated with the dose of TwHF (10mg/d vs 30-60mg/d), negatively related to the dose of MTX (∼10 mg/w vs ∼15 mg/w) and methodological risk of bias of included RCTs, and unrelated to the duration of therapy (12-week vs 24-week). For safety, the addition of TwHF did not increase the risk of most AEs and even reduced the risk of infection and liver AEs. Combining TwHF with MTX may be a superior strategy in the treatment of RA compared with MTX monotherapy. The optimal combination of TwHF+MTX therapy might be TwHF at 30-60mg/d with MTX (∼10 mg/w). Further high-quality double-blind RCTs may be able to change the conclusions of our study, which are still warranted.

Febrile Ulceronecrotic Mucha-Habermann Disease: A Case Report and Review of Literature in the Paediatric Population

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare fulminant variant of pityriasis lichenoides et varioliformis acuta (PLEVA) that is characterized by a large ulceronecrotic appearance with high fever and a variety of systemic symptoms. We report here a case of FUMHD in a 17-year-old male Chinese patient who was treated successfully with a combination therapy of methotrexate, methylprednisolone, and intravenous immunoglobulin. In addition, a literature review was conducted to summarize the key characteristics of paediatric FUMHD cases.

Risk factors associated with relapse after methotrexate dose reduction in patients with rheumatoid arthritis receiving golimumab and methotrexate combination therapy.

To identify risk factors for relapse after methotrexate (MTX) dose reduction in rheumatoid arthritis (RA) patients receiving golimumab (GLM)/MTX combination therapy. Data on RA patients ≥20 years old receiving GLM (50 mg) + MTX for ≥6 months were retrospectively collected. MTX dose reduction was defined as a reduction of ≥12 mg from the total dose within 12 weeks of the maximum dose (≥1 mg/wk average). Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline. A total of 304 eligible patients were included. Among the MTX-reduction group (n = 125), 16.8% of patients relapsed. Age, duration from diagnosis to the initiation of GLM, baseline MTX dose, and DAS28-CRP were comparable between relapse and no-relapse groups. The adjusted odds ratio (aOR) of relapse after MTX reduction was 4.37 (95% CI 1.16-16.38, P = 0.03) for prior use of non-steroidal anti-inflammatory drugs (NSAIDs), and the aORs for cardiovascular disease (CVD), gastrointestinal disease and liver disease were 2.36, 2.28, and 3.03, respectively. Compared to the non-reduction group, the MTX-reduction group had a higher proportion of patients with CVD (17.6% vs 7.3%, P = 0.02) and a lower proportion of prior use of biologic disease-modifying antirheumatic drugs (11.2% vs. 24.0%, P = 0.0076). Attention should be given to RA patients with history of CVD, gastrointestinal disease, liver disease, or prior NSAIDs-use when considering MTX dose reduction to ensure benefits outweigh the risks of relapse.

Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn’s Disease: A Pragmatic Randomized Trial

Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. gov, Number: NCT02772965.

Combination Therapy for Psoriasis with Methotrexate and Other Oral Disease-Modifying Antirheumatic Drugs: A Systematic Review

Although the introduction of biologics and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) has reshaped the treatment paradigm for immune-mediated inflammatory diseases (IMIDs) such as psoriasis, oral conventional synthetic DMARDs (csDMARDs) remain the cornerstone in their treatment. Combinational use of DMARDs is common in rheumatological practice, but for the treatment of many skin diseases, dermatologists typically use a single oral DMARD, with methotrexate (MTX) being the most commonly prescribed csDMARD for psoriasis. To better understand the potential benefits of MTX combination therapy in psoriasis, a literature review was conducted using Medline (PubMed), Embase, Web of Science, and the Cochrane Library, covering articles published from inception untilOctober 2022. Randomized controlled trials, cohort, open-label, and observational studies, and case reports with efficacy and safety results for combination therapy with MTX, csDMARDs, and tsDMARDs or comparisons between MTX monotherapy and combination therapy with other oral DMARDs in psoriasis were included. Studies involving MTX monotherapy alone or sequential treatment with MTX and other oral DMARDs were excluded, as were non-English articles. The results are presented as a systematic review, and the risk of bias was assessed by the corresponding author using the Cochrane Handbook for Systematic Reviews of Interventions, version 6.3, and confirmed by an independent assessor. Eleven studies comprising 494 participants were included in the review. Overall, combination treatment with MTX and other oral DMARDs exhibited good efficacy and tolerability in psoriasis. However, the included studies were primarily small scale or retrospective, and larger prospective randomized trials are needed to provide stronger evidence. This literature review suggests that combination therapy with MTX and csDMARDs may serve as an efficacious treatment for psoriasis patients with an inadequate response to oral DMARD monotherapy.

Comparison of the efficacy and safety of methotrexate alone or in combination with leflunomide in the treatment of juvenile idiopathic arthritis: a double-blind, placebo-controlled, randomized trial.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder in children. Although methotrexate (MTX) is the first line disease-modifying antirheumatic drug for JIA, many patients do not respond well or cannot tolerate MTX. The aim of this study was to compare the effect of combination therapy of MTX and leflunomide (LFN) with MTX in patients who do not respond to MTX. Eighteen patients (2-20 years old) with polyarticular, oligoarticular or extended oligoarticular subtypes of JIA who did not respond to conventional JIA therapy participated in this double-blind, placebo-controlled, randomized trial. The intervention group received LFN and MTX for 3 months while the control group received oral placebo and MTX at a similar dose to the intervention group. Response to treatment was assessed every 4 weeks using the American College of Rheumatology Pediatric criteria (ACRPed) scale. Clinical criteria, including number of active joints and restricted joints, physician and patient global assessment, Childhood Health Assessment Questionnaire (CHAQ38) score, and serum erythrocyte sedimentation ratelevel, did not differ significantly between groups at baseline and at the end of the 4th and 8th weeks of treatment. Only the CHAQ38 score was significantly higher in the intervention group at the end of the 12th week of treatment. Analysis of the effect of treatment on study parameters revealed that only the global patient assessment score differed significantly between groups (p = 0.003). The results of this study showed that combining LFN with MTX does not improve clinical outcomes of JIA and may increase side effects in patients who do not respond to MTX.

Evaluation of cost-effectiveness of various drugs used in the treatment of rheumatoid arthritis: An observational and prospective study

Background: Rheumatoid arthritis (RA) is a joint disorder which affects the quality of life. Early diagnosis and symptomatic treatment can reduce the progression of disease. The treatment is associated with multiple drug therapy for long time. The use of multiple drugs can affect the patient’s economic status. The present study aimed to evaluate the cost-effectiveness of drugs used in the treatment of RA. Aims and Objectives: The aim of the study was to evaluate the cost of mono and multiple drug therapy in the treatment of RA. Materials and Methods: The study was conducted in the Department of Pharmacology and Orthopedic of Adichunchanagiri Institute of Medical Sciences, Karnataka for 6 months. A total of 50 patients were screened and 16 patients were included in the study. All the patients were explained study protocol and informed consent was obtained. Data related to age, gender, past history, and type of drug usage were recorded and analyzed. Microsoft Excel and SPSS (20.0) version were used for analysis. Results: A total of 16 patients were analyzed in the study. The average cost-effective ratio was high for methotrexate and low is hydroxychloroquine. Comparison of cost-effectiveness between different drug combination therapies not showed any significant difference. Combination of non-steroidal anti-inflammatory drugs drug therapy has low cost compared to monoclonal antibody combination therapy. Conclusion: Methotrexate and hydroxychloroquine combination therapy showed a high cost compared to monotherapy. Combination of low-price drugs can reduce the economic burden on patients.

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

ObjectivesTo update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for...

A Comparative Study of Oral Methotrexate and Combination of Oral Methotrexate and Narrow Band Ultraviolet-B in Chronic Plaque Psoriasis

Background: Psoriasis is a chronic common skin condition which alters the skin appearance, causes an inflammation in the outerepidermis, and proliferates the skin epidermal layers. It is influenced by both genomic and other external factors like environmental factors.1The most common lesions are red, scaly, sharply demarcated plaques that appear primarily on extensor surfaces. Psoriasis exhibits a chronic relapsing nature and variable clinical features. The cutaneous lesions are typically thus distinct for clinical diagnosis. Material & Methods: Prospective hospital based observational study. The study was conducted in Department of Department of Dermatology, Narayana Medical College, Nellore, A.P. Patients of chronic plaque psoriasis not responding to any other therapeutic modality. Initially a detailed history regarding the age of onset, the duration of illness, past modalities of treatment, family history of the disease, seasonal variation, other triggering factors, occupation were taken. The patients were explained regarding the duration of treatment, the need for regular follow up of therapy, clinic and probable side effects that could be encountered during treatment. Results: Among all (n=50 including group A and B, 25 of each) participants, relapse of treatment in weeks observed between the range of 6-12, mean was 9 with the standard deviation of 1.6 in group A. For group B relapse of medical regimen in weeks observed between the range 8-12, Mean was 10.5 with the standard deviation of 1.9 which is nearly similar in group A. This results were statistically significant as p= 0.01 where p<0.05. Conclusion: From our study it,we concluded that Combination therapy of oral methotrexate and NBUVB is found to be most effective, feasible from the economic point of view as well as the side effects profile and patient compliance.

Combination of Methotrexate and Leflunomide Is Efficient and Safe for 60 Patients with Rheumatoid Arthritis.

The present work is aimed at exploring the clinical efficacy and safety of methotrexate (MTX) and leflunomide (LEF) combination therapy for rheumatoid arthritis. From June 2019 to June 2021, a total of 120 individuals with rheumatoid arthritis received a diagnosis. Sixty patients each were randomly assigned to the control and observation groups. The observation group received MTX and LEF combo medication while the control group only received MTX treatment. Clinical efficacy, complication incidence, and the alleviation of inflammatory markers, joint pain, and clinical symptoms were compared between the 2 groups. Posttreatment, the observation group had overall response rate of 96.66%, while the control group had 86.67%, with significant differences. Compared with pretreatment, both control and observation group patients showed decreasing trends of IL-1 levels and increasing trends of IL-10 levels posttreatment, with significant differences (P < 0.05). Compared with the control group, patients in the observation group had lower IL-1 and TNF-α levels with significant differences (P < 0.05) and higher levels of IL-10 with significant difference (P < 0.05). In both groups, the pain score and the number of painful joints were much lower than they were prior to treatment. Following treatment, the observation group displayed significantly lower levels of erythrocyte sedimentation rate, rheumatoid factor, and C-reactive protein than the control group (P < 0.05). Clinical measures in the observation group were all lower than those in the control group with statistically significant differences (P < 0.05). Moreover, the incidence rate of adverse reactions showed no significant difference between these 2 groups (P > 0.05). In conclusion, the combination therapy of MTX and LEF is efficacious for rheumatic arthritis.