Etanercept-induced necrotizing crescentic glomerulonephritis in two patients with rheumatoid arthritis

Abstract

We present two patients with rheumatoid arthritis (RA) who developed necrotizing crescentic glomerulonephritis (NCGN) during etanercept therapy. Both patients developed proteinuria and hematuria, and one progressed to renal failure. Renal biopsy revealed NCGN. In both patients, nephritis improved following discontinuation of etanercept and administration of prednisolone. Physicians should be aware of etanercept-induced GN in patients with RA on anti-tumor necrosis factor therapy.     

Etanercept-induced necrotizing crescentic glomerulonephritis in two patients with rheumatoid arthritis

We present two patients with rheumatoid arthritis (RA) who developed necrotizing crescentic glomerulonephritis (NCGN) during etanercept therapy. Both patients developed proteinuria and hematuria, and one progressed to renal failure. Renal biopsy revealed NCGN. In both patients, nephritis improved following discontinuation of etanercept and administration of prednisolone. Physicians should be aware of etanercept-induced GN in patients with RA on anti-tumor necrosis factor therapy.     

Neutropenia in patients with primary antibody deficiency disorders

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases (14 male and 5 female), with a mean age of 10.7+/-5.7 years, were associated with neutropenia (9.2%). The disorders with associated neutropenia were Hyper IgM syndromes (3 of 8), Common variable immunodeficiency (13 of 109), and X-linked agammaglobulinemia (3 of 45). The median age for the onset of disease and diagnosis age were 15 months (1-134) and 3.8 years (6 months-13 years), respectively. The most common infections during the course of illness were pneumonia (13 cases), diarrhea (12 cases), oral candidiasis (9 cases), otitis media (6 cases), sinusitis (6 cases), cutaneous infections (5 cases), and abscess (5 cases). Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.     

Neutropenia in Iranian patients with primary immunodeficiency disorders

Neutropenia may occur in some of the primary immunodeficiency disorders. We reviewed the records of 56 neutropenic patients. The most common disorders were Shwachman-Diamond syndrome, cyclic neutropenia, Kostmann disease, Chediak-Higashi syndrome, hyper IgM syndromes, severe combined immunodeficiency, hyper IgE syndrome, and common variable immunodeficiency.     

Etanercept in adult patients with early onset ankylosing spondylitis

OBJECTIVE: To determine whether twice-weekly subcutaneous etanercept improves the signs and symptoms of adult patients with early onset ankylosing spondylitis (AS). METHODS: A retrospective analysis was performed on a subgroup of patients with AS with onset < 18 years of age from a multicenter, double-blind, placebo-controlled, randomized study of etanercept in the treatment of patients with AS. Twenty patients met criteria and are presented. RESULTS: As early as week four, 5/9 (56%) patients who received etanercept achieved an Assessments in Ankylosing Spondylitis 20% response (ASAS 20) versus only 1/11 (9%) of those who received placebo (p = 0.032). The observed ASAS 20 response continued through week 24, with 6/9 (66%) patients receiving etanercept responding, versus 2/11 of patients receiving placebo (p = 0.025). CONCLUSION: Etanercept improves signs and symptoms of early onset AS in adult patients for at least 24 weeks.     

Etanercept: therapeutic use in patients with rheumatoid arthritis

Tumour necrosis factor (TNF) plays a central part in the pathophysiology of rheumatoid arthritis (RA). TNF initiates signal transduction by interacting with surface bound TNF receptors. Soluble tumour necrosis factor receptors (sTNFRs) act as natural inhibitors of TNF activity. Etanercept, recombinant p75 sTNFR:Fc fusion protein, has received approval from the US Food and Drug Administration for patients with RA and juvenile RA (JRA) who have failed treatment with at least one other drug. Etanercept has demonstrated excellent safety and efficacy in large scale, randomised, double blind, placebo controlled trials of patients with RA and JRA who are refractory to other disease modifying anti-rheumatic drugs. The therapeutic effects mediated by etanercept are rapid and sustained. Combining etanercept with methotrexate was found to be safe and more effective than treatment with methotrexate alone in the treatment of RA. These clinical findings demonstrate that etanercept can result in symptomatic improvement in patients with RA and JRA. Etanercept is an important new addition to the treatment of these diseases.     

Neutropenia in patients with inflammatory arthritis treated with sulphasalazine.

This report describes two patients who developed severe neutropenia one month after starting sulphasalazine (SASP) as treatment for their inflammatory joint disease. Both recovered on stopping the drug. Six further cases (out of a series of 180 patients with inflammatory forms of arthritis receiving SASP therapy) in whom transient leucopenia occurred are also recorded. These patients were able to continue the drug under close supervision. Sulphasalazine is a useful addition to the small number of slow acting antirheumatic drugs (SAARDs) and, despite this complication, is safer than other SAARDs. Careful monitoring of patients is essential, however, particularly in the early stages of treatment, to detect this adverse reversible reaction promptly.     

Etanercept and urticaria in patients with juvenile idiopathic arthritis

Etanercept, a tumor necrosis factor receptor p75 Fc fusion protein (TNFR:Fc; Enbrel), has preliminarily been shown to be effective in the management of methotrexate-resistant polyarticular juvenile idiopathic arthritis (JIA). Reported side-effects have been minor, for example injection site reactions and upper respiratory tract infections, not necessitating discontinuation of the medication (1, 2). We report on 2 patients who developed an urticaria-like rash with prurigo appearing bilaterally on the extensor surfaces of the elbows subsequent to etanercept injections.     

Etanercept and uveitis in patients with juvenile idiopathic arthritis

OBJECTIVES: Etanercept has been shown to be effective for the treatment of juvenile idiopathic arthritis (JIA). The therapeutic efficacy of etanercept for chronic uveitis, a major complication of JIA, has not been evaluated so far. Therefore, the appearance of chronic anterior uveitis and associated complications in JIA patients treated with etanercept was evaluated. METHODS: Questionnaires were sent to paediatric rheumatologists treating a total of 310 JIA patients with etanercept. RESULTS: Two hundred and twenty-nine questionnaires (74%) were returned. Before institution of etanercept, 31 patients (13.5%) had a history of uveitis with a total of 102 flares. Twenty-eight patients belonged to the high-risk groups of the oligoarticular and seronegative polyarticular subtypes. Upon commencing etanercept, 32 courses of uveitis occurred in 19 patients and in two further patients (1%) in whom uveitis occurred for the first time. Twenty of them belonged to the high-risk group. Uveitis during etanercept therapy occurred in 12 of 15 patients (80%) with more than one course of uveitis, and in seven of 16 patients (44%) with only one course before etanercept therapy. Complications were noted in 12 patients before and in eight during etanercept treatment. In 87% of the uveitis patients, arthritis demonstrated a significant or complete response. CONCLUSION: During treatment with etanercept, there were both relapses and first courses of uveitis. In addition, the frequency and severity of uveitis seemed not to be influenced by etanercept. In particular, patients with relapsing uveitis before institution of etanercept treatment remain at high risk of the development of uveitis flares despite etanercept treatment.     

Etanercept therapy in patients with a positive tuberculin skin test

INTRODUCTION: Etanercept (Enbrel), a tumor necrosis factor-alpha (TNF-alpha) antagonist, is commonly used for the treatment of a variety of rheumatic diseases. Tuberculosis (TB) infections have been associated with chronic TNF-alpha blocking therapy, and there is concern that such therapy may predispose patients to TB reactivation. In this study, we attempted to evaluate the frequency of latent TB reactivation among patients treated with etanercept. METHODS: All patients with either a positive purified protein derivative (PPD) for TB or a previous history of therapy for latent TB infection (LTBI) who were prescribed etanercept in the division of rheumatology at John H. Stroger Jr Hospital of Cook County prior to November 2005 were enrolled in this study. A retrospective chart review was performed looking for evidence of active TB infection during etanercept treatment. RESULTS: Forty-eight patients with a positive PPD were treated with etanercept, and followed for an aggregate of 818 patient-months of etanercept exposure, with a mean follow-up period of 17 months (range 5 to 48 months); all patients had at least one follow-up visit. Forty-four patients (92%) were fully or partially treated with LTBI therapy prior to initiation of etanercept. Chest roentgenograms were available for review in 43 patients, ten of which had evidence of old granulomatous disease. No cases of active TB were described during the study period. CONCLUSIONS: In this small retrospective analysis, none of the 48 patients with positive PPDs who were treated with etanercept for average of 17 months developed active TB.     

Etanercept in the treatment of adult patients with Still's disease

OBJECTIVE: To evaluate the safety and efficacy of etanercept in the treatment of adult patients with Still's disease. METHODS: Twelve adult patients who met criteria for Still's disease and had active arthritis were enrolled in a 6-month open-label trial of etanercept given in biweekly doses of 25 mg. The mean disease duration at study entry was 10.7 years. All patients had been treated unsuccessfully with other disease-modifying antirheumatic drugs. Efficacy was evaluated according to American College of Rheumatology (ACR) improvement criteria, and adverse events were recorded. RESULTS: Ten patients successfully completed the study; 2 withdrew due to disease flare. In 4 patients, the dosage of etanercept was increased from 25 mg biweekly to 25 mg 3 times per week. Seven patients met ACR 20% response criteria. Of these 7 responders, 4 met ACR 50% response criteria and 2 met ACR 70% response criteria. Among the 3 patients with systemic features of Still's disease (fever and rash), improvement in these features was seen in 1; the arthritis did not improve in any of these 3 patients. Except in the 2 patients who withdrew due to disease flare (rash, fever, and arthritis), no other significant adverse events occurred. CONCLUSION: In this initial study of etanercept therapy for Still's disease in the adult, this treatment resulted in improvement in the arthritis and was well tolerated. Additional trials should be performed to elucidate the effects of tumor necrosis factor inhibitors in Still's disease.     

Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis

OBJECTIVE:. To assess the efficacy and safety of etanercept in a large cohort of children with refractory systemic onset juvenile rheumatoid arthritis (SOJRA). METHODS: Standardized questionnaires were sent to US pediatric rheumatologists about patients with SOJRA treated with etanercept. Data were collected at baseline and at the last visit on etanercept. Response to treatment was assessed and compared to baseline as the mean percentage reduction in the following: acute phase reactants, prednisone dose, active joint count, and physician global assessment of disease activity. Response was defined as poor if the mean reduction was < 30%, fair if 30% to < 50%, good if 50% to < 70%, and excellent if > 70%. RESULTS: We analyzed data obtained by survey of 82 SOJRA patients treated with etanercept for a mean of 25 months. Poor response to treatment was observed in 45% of the children, fair response in 9%, good in 13%, and excellent in 33%. Baseline steroid therapy could be discontinued in 27/59 (46%) patients. One or more disease flares occurred in 45% of all patients. Twenty-nine patients (35%) discontinued therapy, mostly due to lack of response or flare. There were 32 adverse event reports, most not considered serious, except for 2 cases of macrophage activation syndrome. CONCLUSION: In this cohort of children with SOJRA, 46% had a good or excellent response, and most were able to reduce concomitant corticosteroid doses. The response to etanercept was fair or poor in more than half our study population, and disease flares were common. Due to the unique cytokine profile of SOJRA, tumor necrosis factor blockade may not be the optimal therapeutic approach for children with treatment-resistant SOJRA.     

Etanercept treatment in rheumatoid arthritis patients with chronic kidney failure on predialysis

Rheumatoid arthritis (RA) patients with chronic kidney failure are intolerant to most disease-modifying antirheumatic drugs (DMARDs) and NSAIDs due to their potential toxicities. Although the tumor necrosis factor (TNF) inhibitors have emerged as a highly effective treatment for RA, their safety and efficacy in RA patients with chronic kidney failure have not been well reported. We retrospectively evaluated the safety and efficacy of etanercept treatment in RA patients with chronic kidney failure. We describe three RA patients with chronic kidney failure who had been treated with DMARDs, steroids and NSAIDs, but were discontinued from these classical agents due to several side effects and nephrotoxicity. The patients were treated with 25 mg of etanercept once or twice a week. We evaluated disease activity and used decreasing renal function and increasing number of infections to monitor safety. All three patients improved after starting etanercept treatment and their steroid requirements were decreased. Linear relationships between Modification of Diet in Renal Disease study equation (MDRD) glomerular filtration rate (GFR) and time were observed. Thus, in all patients, the changes in GFR did not represent superimposed acute drug toxicity, but rather chronic progressive renal failure. These cases show that etanercept may be a safe and effective treatment option for RA patients with chronic kidney failure.     

Etanercept reduces the oxidative stress marker levels in patients with rheumatoid arthritis

This study was performed to evaluate the effects of the TNF-α inhibitor etanercept on oxidation stress markers representing DNA damage, lipid peroxidation, and protein glycosylation. Twenty-two rheumatoid arthritis (RA) patients underwent etanercept treatment. The levels of serum total, urinary total, and urinary free pentosidine, which is an advanced glycation end-product (AGE), of urinary N^ε-hexanoyl lysine (N^ε-HEL), and of 8-hydroxy-deoxy guanosine (8-OHdG) were measured at baseline and at 3 and 6 months after the initial treatment with etanercept. Serum total and urinary total pentosidine levels were reduced at 6 months after the initial treatment with etanercept, and urinary free pentosidine levels were reduced at 3 and 6 months. Urinary N^ε-HEL levels were also reduced at 3 and 6 months, and urinary 8-OHdG levels were reduced at 6 months. Serum total and urinary total pentosidine levels in RA patients correlated with the number of swelling joints and tender joints, and urinary total pentosidine levels correlated with the Disease Activity Score using 28 joints (DAS28). This study demonstrated that etanercept acts as a regulator against pentosidine formation, oxidative DNA damage, and lipid peroxidation in RA patients.