Infliximab in rheumatoid arthritis

Current Rheumatology Reports -     

Infliximab treatment of rheumatoid arthritis

Infliximab was the first anti-TNF agent used to treat rheumatoid arthritis to provide proof of concept of the role of TNF-alpha in this condition. It has become widely used since, principally as an effective treatment in combination with methotrexate, but also as monotherapy for the treatment of Crohn's disease, ankylosing spondylitis,and psoriatic arthritis. The benefits of infliximab in controlling signs and symptoms, improving quality of life, preventing structural joint damage, and possible healing of bone provide an important option for the treatment of rheumatoid arthritis.     

Infliximab in active early rheumatoid arthritis

Objective: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA).     

Infliximab treatment maintains employability in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate the impact of infliximab therapy on the employment status of patients with early rheumatoid arthritis (RA). METHODS: Methotrexate (MTX)-naive patients with active early RA were randomly allocated to receive MTX plus placebo or MTX plus infliximab (3 mg/kg or 6 mg/kg) at weeks 0, 2, and 6 and then every 8 weeks through week 46. Data for patients younger than age 65 years were included in the analyses. A patient was categorized as employable if he or she was employed or felt well enough to work if a job were available. RESULTS: The change in actual employment was not significantly different between patients receiving MTX plus infliximab and those receiving MTX plus placebo (0.5% versus 1.3%; P > 0.5). However, the proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the group receiving MTX plus infliximab compared with that in the group receiving MTX alone (8% versus 14%; P = 0.05). Patients who were treated with infliximab plus MTX had a significantly greater likelihood of improvement rather than deterioration in employability (odds ratio 2.4; P < 0.001); this likelihood was not significantly greater in patients receiving MTX alone. The proportion of employed patients who lost workdays during the trial was smaller in the MTX plus infliximab group than in the MTX-alone group (P = 0.010). CONCLUSION: The actual employment rates among patients in the 2 treatment groups were not different. However, patients with early RA who were treated with MTX plus infliximab had a higher probability of maintaining their employability compared with those who were treated with MTX alone.     

Infliximab treatment in a patient with rheumatoid arthritis on hemodialysis

We describe a 60-year-old woman with active rheumatoid arthritis (RA) and endstage renal disease secondary to hypertensive nephrosclerosis undergoing hemodialysis. She had tried multiple antirheumatic medications; however, their usefulness was limited due to toxic side effects or lack of efficacy. She was then treated with chimeric antitumor necrosis factor monoclonal antibody (infliximab), which resulted in immediate improvement in clinical and laboratory measures. After about 2 years of therapy, no side effects have been observed. This report expands the spectrum of infliximab to include RA patients with renal insufficiency.     

Infliximab treatment in a patient with rheumatoid arthritis on haemodialysis

SIR, Anti-tumour necrosis factor (TNF) has been shown to bevery effective in rheumatoid arthritis (RA). Patients with RAwith renal failure are difficult to treat. Special attentionis required to the possible increase in toxicity and to doseadjustment of the drugs used to treat this disease. We reportour experience in treating such a patient with infliximab, amonoclonal TNF antagonist. A 45-yr-old female university professor presented in April 2002with a 2-month history of painful and swollen joints of thesmall joints of both hands, wrists, knees, elbows and shouldersassociated with morning stiffness of 2–3 h duration. In 1984 she was diagnosed with chronic glomerulonephritis ofno obvious cause and in 1985 she     

Infliximab treatment reduces complement activation in patients with rheumatoid arthritis

BACKGROUND: Tumour necrosis factor (TNF) blocking agents decrease C reactive protein (CRP) levels in rheumatoid arthritis (RA). It has been shown that CRP may contribute to complement activation in RA. OBJECTIVE: To assess the effect of intravenous infliximab treatment on complement activation, especially that mediated by CRP, in RA. METHODS: 35 patients with active RA (28 joint count Disease Activity Score (DAS28) >4.4) were treated with intravenous injections of infliximab (3 mg/kg, at weeks 0, 2, 6, 14, and 22). Clinical response and plasma levels of complement activation products, of CRP and of CRP-complement complexes, which are specific markers for CRP mediated complement activation, were assessed at the indicated time points up to 22 weeks. The relationship between CRP and CRP-complement complexes was analysed by paired t test between two time points and by generalised estimated equation, to test differences of variables over time. RESULTS: At 2 weeks after the first dose, infliximab significantly reduced overall C3 and C4 activation and plasma levels of CRP and CRP-complement complexes were also significantly reduced at this time point. The effects of infliximab on CRP and complement continued throughout the observation period and were more pronounced in patients with a good response to infliximab treatment. CONCLUSION: Treatment with infliximab decreases plasma levels of CRP and CRP dependent complement activation products and concomitantly may reduce complement activation in RA. Complement activation may be among the effector mechanisms of TNF in RA.     

Infliximab therapy in established rheumatoid arthritis: an observational study

PURPOSE: To investigate the efficacy, toxicity and drug discontinuation rate in an observational study of patients with established rheumatoid arthritis treated with infliximab. SUBJECTS AND METHODS: Between September 1999 and June 2003, we enrolled 84 patients with rheumatoid arthritis who were being treated with infliximab. All patients met the American College of Rheumatology criteria for rheumatoid arthritis and had been refractory to (or did not tolerate) at least two disease-modifying antirheumatic drugs. Patients entering the study had a negative purified protein derivative skin test, were fully informed about the treatment regimen, and were followed up at predefined times according to a standardized protocol. Data concerning infliximab dosage, tolerability, adverse events, concomitant therapy, dosage interval, and drug discontinuation were all recorded. In addition, the clinical and laboratory variables according to the American College of Rheumatology 20% and 50% response criteria and the disease activity score for the 28 joint indices were also recorded. RESULTS: There were 61 women and 23 men with a mean age of 59 +/- 8 years and mean disease duration of 11 +/- 6 years. Seventy-five percent (63/84) were seropositive for IgM rheumatoid factor. After the first year of treatment, 84.5% of patients continued to be treated with infliximab, whereas this percentage was 73% after the second year and 59% after the third year of treatment. The American College of Rheumatology 20% response criteria was met by 59/84 (70%) of patients, and 38/84 (45%) of the patients achieved the 50% response criteria in the first year of treatment. At the second year of therapy, the American College of Rheumatology 20% response criteria were reached by 35/84 (42%) of the patients and the 50% response criteria by 27/84 (32%). At the third year of treatment with infliximab, the American College of Rheumatology 20% and 50% response criteria were achieved by 13/84 (15.5%) and 10/84 (12%) of the patients, respectively. Twenty-eight of eighty-four (33%) patients discontinued infliximab therapy. The risk of drug discontinuation decreased with the concomitant use of methotrexate. The main reasons for drug discontinuation were adverse drug reactions (16/84, 19%), followed by lack of efficacy (9/84, 11%). The main reasons for drug discontinuation due to side effects were immediate hypersensitivity reactions (9/84, 11%) and infections (6/84, 7%). CONCLUSION: Infliximab was found to be an alternative treatment with a relatively acceptable toxicity profile, despite the fact that two patients developed pulmonary tuberculosis. After the third year of therapy, 59% of patients continued to be treated with infliximab. The concomitant use of methotrexate was associated with the continuation of infliximab therapy.     

Infliximab and methotrexate as induction therapy in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate the efficacy of infliximab plus methotrexate (MTX) as induction therapy in patients with early rheumatoid arthritis (RA). METHODS: Disease-modifying antirheumatic drug (DMARD)-naive patients with active, early RA who were included as group 4 of the BeSt study were initially treated with infliximab (3 mg/kg) in combination with MTX (25 mg/week). The Disease Activity Score (DAS) was measured every 3 months. In patients with persistent low disease activity (DAS 2.4, the infliximab dosage was increased (maximum 10 mg/kg), and they were subsequently switched to another DMARD. Except for intraarticular administration, corticosteroids were not permitted. Functional ability and the modified Sharp/van der Heijde score were determined after 2 years of therapy. RESULTS: Of the 120 patients, 67 responders (56%) had persistent low disease activity and discontinued infliximab after a median of 9.9 months, with a median MTX dosage of 10 mg/week after 2 years. Ten other patients experienced a disease flare after discontinuation and resumed infliximab after a median of 3.7 months. Thirteen patients did not achieve persistent low disease activity and received infliximab at various dosages. Treatment was unsuccessful in 30 patients. In the 67 responders, the progression of joint damage was lower than in the 30 patients in whom treatment failed. CONCLUSION: Fifty-six percent of patients with active early RA, initially treated with infliximab plus MTX, could discontinue infliximab after achieving a DAS of 相似文献   

Infliximab and leflunomide combination therapy in rheumatoid arthritis: an open-label study

OBJECTIVE: To study the safety and efficacy of infliximab plus leflunomide combination therapy in adult rheumatoid arthritis (RA). METHODS: Twenty patients with active RA received leflunomide 100 mg for 3 days followed by 20 mg daily for 32 weeks. At week 2 all patients started infliximab 3 mg/kg, and received a further four infusions at weeks 4, 8, 16 and 24. RESULTS: Adverse events led to 11 patients being withdrawn before the end of the study. The commonest adverse event was pruritis associated with an eczematous rash. Other serious reactions included infliximab infusion reactions in four patients and Stevens-Johnson syndrome in one. There was no relationship between the serum concentration of A77 1726, the active metabolite of leflunomide, and adverse events. The mean Disease Activity Score (DAS28) fell from 7.18 at week 0 to 5.18 (P<0.0001, paired t-test) at week 4 and remained between 3.85 and 4.85 up to week 32. In those patients remaining on treatment, more than 80% achieved an ACR20 response from week 8 to week 28, and up to 46% achieved an ACR70 response. CONCLUSION: Infliximab plus leflunomide combination therapy appears to be highly efficacious in the treatment of adult RA. However, widespread use may be limited by adverse events, which were common and in some cases severe.     

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Infliximab treatment in combination with cyclosporin A in patients with severe refractory rheumatoid arthritis

OBJECTIVE: To investigate whether infliximab can be used in combination with cyclosporin A (CsA) in patients with refractory rheumatoid arthritis (RA) who cannot tolerate methotrexate (MTX). MATERIALS AND METHODS: Eighteen patients with refractory RA receiving low dose CsA (2 mg/kg/day) and prednisone (5 mg/day) were treated with intravenous infliximab. The patients were given infliximab (3 mg/kg weight) at 0, two, six, and every eight weeks thereafter for a total period of 12 months. Clinical improvement was evaluated according to the American College of Rheumatology (ACR) 20% response criteria. RESULTS: Eighty per cent of patients receiving the combination treatment with CsA and infliximab achieved the 20% ACR criteria for response to treatment, whereas 39% satisfied the 50% response criteria. In addition, a 76% reduction in swollen and tender joint count was found. Finally, a reduction in C reactive protein and erythrocyte sedimentation rate was maintained throughout the study. In general, treatment was well tolerated, with minimal adverse drug reactions. Two patients dropped out; one because of an immediate hypersensitivity reaction and the other because of the development of pulmonary tuberculosis. CONCLUSION: Multiple infusions of infliximab and low doses of CsA improve patients with refractory RA. It seems that CsA may be an alternative disease modifying drug to be used in combination with infliximab in patients with refractory RA who cannot tolerate MTX.     

Infliximab treatment reduces the serum levels of interleukin-23 in patients with rheumatoid arthritis

Abstract

In this study, we investigated the effect of the antitumor necrosis factor alpha (anti-TNF-α) antibody, infliximab, combined with methotrexate (MTX) and MTX alone on the serum levels of interleukin (IL)-23 and IL-17 in rheumatoid arthritis (RA) patients. Infliximab combined with MTX was administered to 26 patients with RA (infliximab group), and MTX alone was given to 20 patients with RA (MTX group). We evaluated clinical and laboratory parameters, including the Disease Activity Scores of 28 joints (DAS28) and serum levels of IL-23 and IL-17 at baseline and at 14 and 30 weeks after the initial treatment with these drugs. Single regression analysis was performed between the levels of serum IL-23 and other clinical and laboratory parameters at baseline before the initial treatment with infliximab or MTX. A significant reduction of DAS28 scores was observed in both the infliximab and the MTX group at 14 and 30 weeks after the initial treatment. A significant decrease in serum levels of IL-23 was observed in the infliximab group but not in the MTX group at 14 and 30 weeks after the initial treatment. Serum IL-17 levels did not show a significant change during the follow-up period. At baseline, before the initial treatment with infliximab or MTX, serum IL-23 levels showed a significant correlation with DAS28 and the number of swollen joints. This study indicated that the reduction of serum IL-23 levels in RA patients was a novel action of infliximab.     

Infliximab but not methotrexate induces extra-high levels of VLDL-triglyceride in patients with rheumatoid arthritis

OBJECTIVE: Tumor necrosis factor (TNF-alpha), a pivotal inflammatory cytokine, is known to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA). We examined the effects of anti-TNF-alpha antibody (infliximab, IFX) compared with methotrexate (MTX) on lipid profiles in patients with RA. METHODS: We selected retrospectively all patients with refractory RA (n = 32) who achieved a successful outcome (DAS-28 score < 2.6) in 6 months with IFX treatment, and control groups of age- and sex-matched patients with active RA treated with MTX and healthy participants. We traced fasting serum levels of total cholesterol (TCHO) and triglyceride (TG) for 6 months and used an online dual enzymatic method for simultaneous quantification of cholesterol (CHO) and TG by high performance liquid chromatography (HPLC). RESULTS: Mean C-reactive protein levels (baseline 4.5) fell to below 1 in 6 months. MTX treatment elevated and normalized TCHO and TG levels. IFX treatment, however, preferentially induced extra-high TG levels. HPLC analyses identified similar CHO profiles between patients treated with IFX or MTX, but IFX selectively induced a huge VLDL-TG peak. Statins successfully controlled these extra-high TG levels. CONCLUSION: In patients successfully treated with IFX or MTX, CHO levels were elevated and normalized, but IFX treatment preferentially induced extra-high levels of VLDL-TG. Thus, there is differential regulation of the lipid profile between IFX and MTX, necessitating careful attention to TG levels with IFX treatment.     

Infliximab does not activate replication of lymphotropic herpesviruses in patients with refractory rheumatoid arthritis

OBJECTIVE: The reactivation of human lymphotropic herpesviruses can be related to the intensity of immunosuppression. We analysed the risk of reactivation of lymphotropic herpesviruses in patients with refractory rheumatoid arthritis treated with an anti-tumour necrosis factor-alpha (TNF-alpha) agent (infliximab). METHODS: Fifteen patients were treated with infliximab (3 mg/kg) at weeks 0, 2 and 6. Samples of both plasma and peripheral blood mononuclear cells (PBMC) were obtained before treatment (week 0) and before each infusion at weeks 2 and 6. Samples were analysed using a multiplex qualitative polymerase chain reaction (PCR) for lymphotropic herpesviruses. Quantification of cytomegalovirus (CMV) viral load (copies/ml) was performed using quantitative PCR. Reactivation was defined as the presence of viral DNA in plasma. Latent infection was defined as the presence of viral DNA in PBMC samples but not in plasma. RESULTS: On baseline, latent CMV infection was detected in eight patients (53.3%), human herpesviruses-6 (HHV-6) in two (13.3%), Epstein-Barr virus (EBV) in seven (46.6%), CMV + HHV-6 in one (6.6%), CMV + EBV in two (13.3%) and HHV-6 + EBV in one (6.6%). Viral reactivation related to infliximab treatment was not observed. There was only one patient who had HHV-6 reactivation, but this was already detected in the baseline sample. CONCLUSIONS: Infliximab treatment does not induce replication of human lymphotropic herpesviruses in patients with rheumatoid arthritis. Thus, herpesviruses prophylaxis would not be indicated in these patients.     

Infliximab treatment reduces the serum levels of interleukin-23 in patients with rheumatoid arthritis

In this study, we investigated the effect of the antitumor necrosis factor alpha (anti-TNF-α) antibody, infliximab, combined with methotrexate (MTX) and MTX alone on the serum levels of interleukin (IL)-23 and IL-17 in rheumatoid arthritis (RA) patients. Infliximab combined with MTX was administered to 26 patients with RA (infliximab group), and MTX alone was given to 20 patients with RA (MTX group). We evaluated clinical and laboratory parameters, including the Disease Activity Scores of 28 joints (DAS28) and serum levels of IL-23 and IL-17 at baseline and at 14 and 30 weeks after the initial treatment with these drugs. Single regression analysis was performed between the levels of serum IL-23 and other clinical and laboratory parameters at baseline before the initial treatment with infliximab or MTX. A significant reduction of DAS28 scores was observed in both the infliximab and the MTX group at 14 and 30 weeks after the initial treatment. A significant decrease in serum levels of IL-23 was observed in the infliximab group but not in the MTX group at 14 and 30 weeks after the initial treatment. Serum IL-17 levels did not show a significant change during the follow-up period. At baseline, before the initial treatment with infliximab or MTX, serum IL-23 levels showed a significant correlation with DAS28 and the number of swollen joints. This study indicated that the reduction of serum IL-23 levels in RA patients was a novel action of infliximab.