Leflunomide Combination Therapy Research Articles

Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjögren's disease

Primary Sjögren disease (pSD) is an autoimmune disease characterized by lymphoid infiltration of exocrine glands leading to dryness of the mucosal surfaces and by the production of autoantibodies. The pathophysiology of pSD remains elusive and no treatment with demonstrated efficacy is available yet. To better understand the biology underlying pSD heterogeneity, we aimed at identifying Consensus gene Modules (CMs) that summarize the high-dimensional transcriptomic data of whole blood samples in pSD patients. We performed unsupervised gene classification on four data sets and identified thirteen CMs. We annotated and interpreted each of these CMs as corresponding to cell type abundances or biological functions by using gene set enrichment analyses and transcriptomic profiles of sorted blood cell subsets. Correlation with independently measured cell type abundances by flow cytometry confirmed these annotations. We used these CMs to reconcile previously proposed patient stratifications of pSD. Importantly, we showed that the expression of modules representing lymphocytes and erythrocytes before treatment initiation is associated with response to hydroxychloroquine and leflunomide combination therapy in a clinical trial. These consensus modules will help the identification and translation of blood-based predictive biomarkers for the treatment of pSD.

Pharmacovigilance of Herb-Drug Interactions: A Pharmacokinetic Study on the Combined Administration of Tripterygium Glycosides Tablets and Leflunomide Tablets in Rats by LC-MS/MS.

A popular and widely used combination therapy of leflunomide (LEF) and Tripterygium glycosides tablets (TGTS) has become a valuable clinical tool in China for the treatment of rheumatoid arthritis. This regimen has not been evaluated either in terms of interaction or toxicity, even given the rising concerns about LEF’s prolonged elimination half-life and TGT’s narrow therapeutic index, in addition to the current trend of using high doses of LEF. Thus, this study determines the potential adverse drug reactions between these two medicines. Reliable validated LC-MS/MS methods were used for the determination of teriflunomide (TER, the only active metabolite of LEF), and the main components of TGT: wilforlide A, wilforgine, wilfortrine, wilfordine, and wilforine. The results obtained from this investigation, as paralleled with the control groups, revealed that the Cmax and AUC0-t of TER were significantly decreased with separate co-administration, as the Cmax and AUC0-t were 30.17 ± 1.55 μg/mL and 24.47 ± 2.50 μg/mL, 374.55 ± 15.54 μg h/mL and 336.94 ± 21.19 μg h/mL, respectively (p < 0.05). Meanwhile, the pharmacokinetic profiles of the main components of TGT have also been affected by separate co-administration in rats. Therefore, herb–drug interactions between LEF and TGT have been proven.

Efficacy of Wushaoshe Qufeng Tablet and leflunomide combination therapy in the management of rheumatoid arthritis, and its influence on incidence of adverse drug reactions

Purpose: To study the effectiveness and safety of combined use of Wushaoshe Qufeng tablets andleflunomide in the treatment of rheumatoid arthritis patients.Methods: A retrospective trial was conducted among 120 patients with rheumatoid arthritis hospitalized in Heyuan Hospital of Traditional Chinese Medicine, Heyuan, from February 2020 to February 2021. The patients were equally divided into study group (n = 60) and control group (n = 60). Both groups received conventional treatment. in addition, the control group received leflunomide, whereas the experimental group received Wushaoshe Qufeng tablets. The two groups were compared with respect to laboratory indicators, TCM syndrome scores, and adverse events.Results: The post-treatment TCM syndrome scores was lower in the experimental group versus control group (p &lt; 0.001). After treatment, the study group was superior to the control group in terms of their biochemical indicators (p &lt; 0.001). Safety profile was better in the study group than in the control group (p &lt; 0.05). Treatment effectiveness was significantly higher in the study group than in the control group (p &lt; 0.05).Conclusion: Combined treatment of rheumatoid arthritis patients with Wushaoshe Qufeng tablets and leflunomide shows improved biochemical indicators, mitigates clinical symptoms, and enhances treatment effectiveness. Moreover, the combination therapy is safe, and therefore, should be considered for the management of rheumatoid arthritis patients.

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

Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) are the preferred first-line treatment in patients with psoriatic arthritis, although there is a paucity of evidence for the efficacy of conventional synthetic DMARDs and especially their combination. We aimed to investigate whether a combination of methotrexate plus leflunomide is superior to methotrexate monotherapy at improving disease activity in patients with psoriatic arthritis. This single centre, investigator-initiated, double-blind, randomised, placebo-controlled trial was conducted at Sint Maartenskliniek in the Netherlands (locations included Boxmeer, Geldrop, Woerden, and Nijmegen). Patients aged 16 years or older with a clinical diagnosis of psoriatic arthritis and active disease (defined as two or more swollen joints; dactylitis counting as one swollen joint) were included. Patients were randomly allocated (1:1) and stratified by high disease activity (psoriatic arthritis disease activity score [PASDAS] ≥5·4) to either methotrexate plus leflunomide (combination therapy) or methotrexate plus placebo (monotherapy), using computer-generated stratified variable block randomisation. In both groups, patients received oral methotrexate 15 mg per week for the first 4 weeks and 25 mg per week thereafter combined with two leflunomide 10 mg tablets once per day or two placebo tablets. During the study period, the patients, nurses, researchers, and treating physicians were all masked to treatment allocation. The primary outcome was the difference in mean PASDAS at week 16, adjusted for baseline PASDAS, between the combination and monotherapy groups, assessed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register (NL7404) on Dec 3, 2018. Between Feb 19, 2019, and March 11, 2021, 82 patients were screened for eligibility. Four patients were ineligible and 78 were enrolled and randomly assigned to either methotrexate plus leflunomide (n=39) or methotrexate plus placebo (n=39). 50 (64%) of 78 patients were male, 28 (36%) were female, and the median age of patients was 55·0 years (IQR 42·0-64·0). Methotrexate plus leflunomide combination therapy was superior to methotrexate monotherapy at week 16 (PASDAS 3·1 [SD 1·4] vs 3·7 [SD 1·3]; treatment difference -0·6, 90% CI -1·0 to -0·1; p=0·025). There were no study deaths. The most frequently occurring adverse events were nausea or vomiting (17 [44%] of 39 patients in the methotrexate plus leflunomide group vs 11 [28%] of 39 in the methotrexate plus placebo group), tiredness (9 [23%] vs 13 [33%]) and elevated alanine aminotransferase (12 [31%] vs 7 [18%]. Generally, the incidence of mostly mild adverse events was higher in the methotrexate plus leflunomide group than in the methotrexate plus placebo group. Methotrexate plus leflunomide combination therapy results in greater improvement in disease activity according to PASDAS in patients with psoriatic arthritis. However, methotrexate plus leflunomide combination therapy is less well tolerated than methotrexate monotherapy. Regional Junior Researcher Grant from the Sint Maartenskliniek.

Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a descriptive cohort study assessing trends in patient characteristics in Switzerland

ObjectivesTo identify differing patient characteristics at the time of stop and restart of biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA), stratified by stop reason.DesignExplorative descriptive...

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).

Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report

BackgroundTreatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy.Case presentationA 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs. Comorbidities included a urinary tract infection, metabolic syndrome with obesity, type-2 diabetes without necessity for insulin or oral antidiabetics, and non-alcoholic fatty liver disease. Laboratory results showed acute liver failure, oliguric acute kidney injury, thrombocytopenia, and schistocyte-positive, Coombs-negative hemolytic anemia. On admission, her ADAMTS13 activity was decreased, and her leflunomide plasma level was elevated (120 μg/l). Due to severe hypoalbuminemia, an intravascular hypovolemia, and severe metabolic alcalosis with hypokalemia were found.For the newly diagnosed thrombotic microangiopathy, leflunomide and methotrexate were discontinued, and 4 units of fresh-frozen plasma were given. Steroid therapy was administered for 5 days, until thrombotic thrombocytopenic purpura was excluded. Intravenous human albumin, oral vitamin K, and cholestyramine were administered for liver failure and leflunomide overdosage, respectively. Liver biopsy revealed a non-alcoholic fatty liver disease transforming into liver cirrhosis. After 2 weeks, our patient was discharged. However, within 3 weeks after discharge, our patient was rehospitalized for a relapse of acute liver failure, urinary tract infection, and influenza. Leflunomide and methotrexate were not reintroduced before or thereafter. Over a period of 11 months after discharge, her thrombotic microangiopathy subsided, and her renal and liver function fully recovered.ConclusionsUnder a combination of leflunomide and methotrexate, liver toxicity and, for the first time, thrombotic microangiopathy occurred as side effects. Non-alcoholic fatty liver disease may have predisposed for the drug-induced liver toxicity.

Comparison of combination therapy with methotrexate and sinomenine or leflunomide for active rheumatoid arthritis: A randomized controlled clinical trial

BackgroundA combination of conventional disease-modifying anti-rheumatic drugs improves the treatment of rheumatoid arthritis but with high side-effects. Methotrexate (MTX) combination therapy that with high therapeutic efficacy and low toxicity is in demand in many countries to replace the use of expensive biological agents. Study designThis study was an open-label, 24-week, parallel randomized controlled trial conducted between November 2015 and December 2017. MethodsPatients were randomly assigned at a 3:2 ratio to receive MTX combined with sinomenine (SIN) at a dose of 120 mg twice daily, or leflunomide (LEF) at a dose of 20 mg once daily. Efficacy and safety were assessed at weeks 4, 12 and 24. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology (ACR)50 response and a European League Against Rheumatism (EULAR) good response at week 24. ResultsA total of 101/120 (84.2%) patients completed 24 weeks of observation. In the intention-to-treat (ITT) analysis, 65.3% of patients treated with MTX + SIN showed improved disease activity as determined by the ACR50 response at week 24 compared to 69.6% of patients treated with MTX + LEF. A similar insignificant pattern was found for the ACR20 and ACR70 responses, as well as the clinical disease activity index, EULAR response, and remission and low disease activity rates between these two treatment groups. The per-protocol analysis showed results consistent with those of the ITT analysis. Notably, significant reductions in gastrointestinal adverse reactions and liver toxicity were found in patients treated with MTX + SIN compared to patients treated with MTX + LEF (p < 0.05). ConclusionConsidering the balance of efficacy and toxicity, the current study provides evidence that MTX + SIN combination therapy is probably one of the choices for treating patients with active rheumatoid arthritis in addition to MTX + LEF combination therapy.

Combination therapy of leflunomide and glucocorticoids for the maintenance of remission in patients with IgG4-related disease: a retrospective study and literature review.

Although glucocorticoids are effective in IgG4-related disease (IgG4-RD), patients may relapse during or after glucocorticoid tapering. Immunosuppressive agents, including leflunomide (LEF), are regarded as steroid-sparing agents in other autoimmune disorders and need to be discussed in the management of IgG4-RD. To identify the efficacy and safety of combination therapy of LEF and glucocorticoids in IgG4-RD. We retrospectively summarised data of patients diagnosed with IgG4-RD between November 2012 and November 2015. Only patients treated with LEF plus glucocorticoids and had been followed up for more than three visits and 6 months were analysed with clinical symptoms, laboratory and imaging findings, treatment protocol, LEF-related adverse events and disease activity reflected by IgG4-RD Responder Index (IgG4-RD RI). A total of 18 patients, including 14 untreated patients and 4 relapsing patients, was included. The mean (SD) onset age was 54.0 (9.6) years. The mean (SD) follow-up period was 12.1 (7.4) months. All patients had active disease with mean (SD) IgG4-RD RI of 15.0 (5.6) at baseline and experienced improvements at 1 month. At the last follow up, the mean (SD) IgG4-RD Responder Index declined to 3.1 (1.7) in all patients and to 2.5 (1.2) in patients without relapse. The mean (SD) dose of GC declined to 6.9 (2.7) mg/day. A total of 12 (66.7%) and 11 (61.1%) patients were in remission at 6 months and the last follow up respectively. Three (16.7%) patients relapsed in clinical course. Two reversible adverse events were observed. The combination therapy of LEF and glucocoticoids is effective and safe in IgG4-RD.

Study of efficacy and safety of methotrexate and leflunomide combination therapy in patients with rheumatoid arthritis (RA) – An audit

Study of efficacy and safety of methotrexate and leflunomide combination therapy in patients with rheumatoid arthritis (RA) – An audit

THU0146 Clinical analysis of hepatitis B virus reactivation associated with non-biological disease-modifying antirheumatic drug(s) in patients with rheumatoid arthritis

BackgroundHepatitis B virus (HBV) reactivation, which refers to the abrupt rise in HBV replication in patients with inactive or resolved hepatitis B and is triggered typically by immunosuppressive chemotherapy in...

SAT0308 Efficacy and toxicity of leflunomide monotherapy versus leflunomide combination therapy with non-biological disease-modifying antirheumatic drugs in psoriatic arthritis

BackgroundAbout 7% of patients (pts) with arthritis are patients with psoriatic arthritis (PsA). After 10 years of PsA 55% of pts have deformity more than 5 joints. Only one trial...

Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis

Combination use of methotrexate (MTX) and leflunomide (LEF) has been proved effective in the treatment of active rheumatoid arthritis (RA). However, previous trials have documented that both are associated with increased incidence of liver toxicity. As active compounds extracted from the roots of the traditional Chinese herb Paeonia lactiflora Pall, total glucosides of paeony (TGP) have been shown to have anti-inflammatory, hepatoprotective and immuno-regulatory activities, without evident toxicity or side effects. In this 24-week, open label, randomized multicenter clinical trial, we investigated the efficacy of TGP and the protective effect on hepatotoxicity in the combination treatment with LEF and MTX for patients with active RA. A total of 204 patients with active RA (DAS28>3.2) recruited from 3 regional referral centers were enrolled and received MTX and LEF combination therapy (MTX 10mg/week plus LEF 20mg/day) with or without TGP for up to 24weeks by randomization. Hepatotoxicity was defined as an increase of at least 1.5-fold the upper limits of normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Significantly less frequent hepatotoxicity was observed in patients with TGP than those without (9.5% vs 34.8%, p<0.001) at 12weeks. The proportion of patients whose ALT or AST levels were >1.5 to ≤2 times and >2 to ≤3 times the ULN were lower in TGP group than the control (1.9% vs 10.1%, 2.9% vs 12.4%, p<0.05 respectively). More patients in the TGP group achieved a European League Against Rheumatism (EULAR) good response or moderate response at 12weeks, although there is no statistical significance. Similar results were observed at 24weeks. Our preliminary study demonstrates the hepatoprotective and additive role of TGP in combination with MTX and LEF in the treatment of active RA.

Effective treatment of Kimura’s disease with leflunomide in combination with glucocorticoids

Kimura's disease (KD) is a rare, benign, chronic inflammatory disease which typically presents as persisting or recurring tumor-like lesions in the head and neck area that can be easily misdiagnosed. We report one patient with KD treated with leflunomide in combination with glucocorticoids and analyzed the literature on treatment of KD. The patient had a recurrent mass in the left upper arm with eosinophilia and elevated serum IgE but no renal involvement. The clinical manifestations improved markedly within 1month, and blood eosinophil count and serum IgE normalized. Corticosteroids were then tapered gradually without recurrence or severe side effects in the 2-year follow-up period. Literature analysis identified four different non-drug interventions and 18 different drugs for treating KD, most of which were obtained from case reports. Our use of combination therapy of leflunomide and glucocorticoids suggests the need for a controlled trial for the treatment of this rare disorder.

Efficacy and tolerability of adalimumab (humira) in patients with active rheumatoid arthritis

Objective: to evaluate the efficacy and tolerability of adalimumab alone and in combination with basic anti-inflammatory drugs (BAIDs) in patients with rheumatoid arthritis (RA), by taking into account the specific features of the course of the disease. Subjects and methods. The study enrolled 30 patients with a verified diagnosis of RA, its high activity by DAS 28, and ineffective previous therapy with standard BAIDs. At the beginning of the study, 20 (66.7%) patients continued taking BAIDs. According to therapy, the patients were divided into 3 groups: 1) 10 (33.3%) patients received subcutaneous adalimumab injections only; 2) 12 (40%) took adalimumab+methotrexate (MT); 3) 8 (26.7%) had adalimumab+leflunomide. The patient groups were matched for age, the duration and activity of RA (by DAS 28), its X-ray stage and seropositivity. Nine (37.5%) patients took oral glucocorticoids (GCs) and 25 (83.3%) received non-steroidal anti-inflammatory drugs (NSAIDs). Two (8.3%) patients had previously been prescribed biological therapies. Adalimumab was subcutaneously injected every 2 weeks for 24 weeks. The quantitative parameters of articular syndrome and blood and urine biochemical and clinical analyses were used to evaluate therapeutic effectiveness. The effect of therapy was evaluated by the ACR and EULAR (DAS 28) criteria. The efficiency of therapy was evaluated 12 and 24 weeks after therapy. Results. The clinical and laboratory effect of adalimumab was noted in 29 (96.7%) of the 30 patients. All the assessed parameters of articular syndrome became significantly lower (p<0.001) by week 12 of therapy and to a greater extent by week 24. Evaluation of the efficiency of adalimumab therapy by the ACR criteria showed that following 12-week therapy, the parameters were decreased by 20% in 87% of the patients and 50% in 16.7%; after 24 weeks, 23.3, 70 and 96.7% achieved very good (ACR 70), good (ACR 50), and satisfactory (ACR 20) effects. Estimation of the time course of changes in the disease activity index (DAS 28) revealed that adalimumab significantly reduced disease activity. Therapeutic effectiveness was also shown as reduced needs for NSAIDs and GCs. Positive clinical and laboratory changes during adalimumab+ MT combination therapy were also demonstrated to be significantly higher than those during adalimumab monotherapy or adalimumab + leflunomide combination therapy. Conclusion. Adalimumab is an effective disease-modifying biological agent. Its benefits may include the rapid development (on days 4-5 on average) and long retention (for 6 months or more) of an effect, a good safety profile (adverse reactions occurred only in 16.7% of the patients), and easiness-to-use.

Comparison of the therapeutic effects of leflunomide and mycophenolate mofetil in the treatment of immunoglobulin A nephropathy manifesting with nephrotic syndrome

To evaluate the therapeutic effects and safety of a combination therapy of leflunomide (LEF) and prednisone for the treatment of immunoglobulin A (IgA) nephropathy manifesting with nephrotic syndrome. 40 patients with IgA nephropathy manifesting with nephrotic syndrome were randomly divided into two groups. The treatment group was administered with a combination therapy of prednisone and LEF, and the control group with a combination therapy of prednisone and MMF. For the following comparison 24-h urinary protein excretion and the serum levels of albumin, cholesterol, and creatinine before and after the therapy were assessed. In the treatment group, the medication was markedly effective in 5 cases and effective in 7 cases; the total efficacy rate was 60.0%. In the control group, the treatment was markedly effective in 5 cases and effective in 8 cases; the total efficacy rate was 65.0%. The IgA levels in both groups decreased after therapy. There were no significant differences between the results for the two groups (p > 0.05). The treatments were well tolerated in both groups. LEF is a safe and effective drug for the treatment of IgA nephropathy manifesting with nephrotic syndrome.

Syringotropic hypersensitivity reaction associated with infliximab and leflunomide combination therapy in a child with psoriatic arthritis

A 17-year-old boy with refractory psoriatic arthritis and alpha-1 antitrypsin deficiency who developed a syringotropic hypersensitivity reaction after 9 months of therapy with infliximab and leflunomide is described. Clinically, our patient showed a vasculitic-like skin rash involving both palms and soles, and histopathological examination revealed a syringotropic lymphocytic infiltrate directed toward the intra-epidermal portion of the eccrine ducts. These features have not been previously associated with infliximab or leflunomide therapy and represent a unique cutaneous hypersensitivity reaction that does not fit any known description of an immune-mediated hypersensitivity reaction.

Leflunomide Treatment in Elderly Patients with Rheumatoid or Psoriatic Arthritis

Disease-modifying antirheumatic drugs (DMARDs) play a crucial role in the treatment of persistent chronic synovitis, such as active rheumatoid arthritis (RA) and spondyloarthritis, by inducing or maintaining disease remission, reducing the frequency of flares or relapses, and allowing corticosteroids to be tapered while maintaining disease control. The aim of this retrospective study was to evaluate the safety of, and adherence to treatment with, leflunomide in elderly RA and psoriatic arthritis patients compared with younger patients. A total of 90 Italian patients (80 with active RA and 10 with psoriatic arthritis) were retrospectively examined at entry and after 24 months' follow-up. Patients were divided into two groups according to age: those aged <or=65 years (n = 50) and those aged >65 years (n = 40). Each patient was analysed for clinical, demographic and laboratory parameters in order to evaluate liver, renal and haematological toxicity. Disease Activity Score including a 28-joint count (DAS28) and physician global assessment of disease activity (MD global) were measured to define disease activity. During the 24-month follow-up period, 30 patients (33.3%) discontinued leflunomide: 17 patients (34.0%) in the group of patients aged <or=65 years and 13 patients (32.5%) in those aged >65 years. There were no differences in treatment withdrawal between the two groups. Overall, 10 patients (11.1%) in the entire study population discontinued leflunomide for lack of efficacy, while 21 (23.3%) discontinued the drug because of adverse effects (one patient withdrew because of both inefficacy and adverse effects). There were no significant differences in efficacy or adverse effects between patients aged <or=65 years and patients aged >65 years. There was also no significant difference in survival rates of leflunomide treatment when patients aged <or=65 years were compared with patients aged >65 years (p = 0.94). There were no significant differences in withdrawal rates in the overall population when leflunomide monotherapy was compared with leflunomide combination therapy. There were also no significant differences in the types of adverse effects associated with monotherapy or combination therapy when the two age groups were compared. Leflunomide is a useful and well tolerated DMARD for the treatment of RA and psoriatic arthritis in the elderly. The safety profile of, and adherence to, leflunomide is not different in older patients with chronic inflammatory joint diseases such as RA or psoriatic arthritis to that observed in younger patients.

Ganciclovir and Leflunomide Combination Therapy for a Patient with Cytomegalovirus Pneumonia after Unrelated Allogenic Stem Cell Transplantation

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality among transplant recipients. The first line standard therapy for CMV pneumonia is treatment with a combination of ganciclovir and immunoglobulin. Nevertheless, the mortality of CMV pneumonia is 30-70%. Leflunomide has been recently reported to have novel anti-CMV activity by inhibiting viron assembly. It is also cheaper and is more easily given orally as compared to ganciclovir. We report here on an allogenic stem cell transplant recipient who developed CMV pneumonia that was refractory to ganciclovir and immunoglobulin. The patient was successfully treated with a combination of leflunomide and ganciclovir.

Tolerability of methotrexate and leflunomide combination therapy for inflammatory arthritis in routine clinical practice: results of a four-centre study

Tolerability of methotrexate and leflunomide combination therapy for inflammatory arthritis in routine clinical practice: results of a four-centre study