Treatment of sarcoidosis with infliximab

BACKGROUND/OBJECTIVES: Many patients with sarcoidosis are unable to tolerate corticosteroids or alternative therapeutic agents due to side effects or have disease refractory to these agents. We report our experience using infliximab to treat such patients. METHODS: A group of patients in whom traditional sarcoidosis therapy failed, either due to drug failure or intolerable side effects, were prescribed infliximab. Their charts were retrospectively reviewed. RESULTS: Ten patients receiving infliximab were reviewed. Nine of the 10 patients reported a symptomatic improvement with therapy, and all 10 demonstrated objective evidence of improvement. A drug reaction developed in one patient after several months of therapy, oral candidiasis developed in one patient, and angioimmunoblastic lymphoma developed in another patient. The corticosteroid dose was reduced in five of the six patients who were receiving corticosteroids at the time of infliximab therapy. CONCLUSION: Infliximab appears to be an effective, safe treatment for patients with refractory sarcoidosis, including such manifestations as lupus pernio, uveitis, hepatic sarcoidosis, and neurosarcoidosis. Infliximab appears to be steroid sparing. Patients receiving the drug should be screened for latent tuberculosis and lymphoproliferative disorders.     

Treatment of psoriatic arthritis and psoriasis vulgaris with the tumor necrosis factor inhibitor infliximab

OBJECTIVE: The aim was to evaluate the efficacy and safety of multiple infusions with achimeric, anti-tumor necrosis factor (TNF)alpha monoclonal antibody (infliximab) in patients with psoriatic arthritis (PsA) and psoriasis vulgaris. METHODS: Over 22 weeks, nine patients with both active psoriasis and PsA received five infusions of 3 mg/kg infliximab. The endpoints included changes in the swollen and tender joints counts, American College of Rheumatology (ACR) preliminary criteria for improvement response rates 20, 50, and 70, and improvement in the psoriasis area and severity index (PASI). RESULTS: The swollen count (SJC) and tender joint count (TJC) fell from means of 5.33+/-2.22 and 17.80+/-4.21 to 1.44+/-1.09 and 9.77+/-0.92, respectively, by week 2 ( P=0.02, P=0.02). This benefit was sustained through week 22 (2.00+/-1.12/7.77+/-3.68, P=0.05/ P=0.002). The ACR 20/50/70 response was achieved in 89%/56%/22% of cases. The mean PASI score improved from 19.04+/-5.41 to 4.91+/-2.51 ( P=0.002). CONCLUSION: Multiple infusions of infliximab were effective and well tolerated in patients with active psoriasis and PsA.     

Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis

OBJECTIVE: To investigate the relationship between serum trough infliximab levels and clinical response to infliximab treatment in patients with rheumatoid arthritis (RA). METHODS: Disease activity and serum trough infliximab levels before and 2, 6, and 14 weeks after initiation of infliximab treatment at a dose of 3 mg/kg in a cohort of 105 patients with RA were assessed. Serum trough infliximab levels in responders and non-responders were compared. Additionally, the clinical responses of patients with high, intermediate, and low serum trough infliximab levels at 14 weeks were compared. RESULTS: After 14 weeks of treatment non-responders had lower serum trough levels of infliximab than responders (median (interquartile range) 0.5 (0.2-2.2) v 3.6 (1.4-8.2) mg/l; p<0.01)). Patients with low serum trough infliximab levels at 14 weeks had significantly less improvement in the 28 joint count Disease Activity Score (DAS28) score than patients with intermediate or high serum trough infliximab levels at 14 weeks. Pretreatment C reactive protein (CRP) levels correlated negatively with serum trough infliximab levels at 14 weeks after the start of treatment (Spearman rank correlation r(s) = -0.43, p<0.001). CONCLUSION: Serum trough levels of infliximab correlate with the clinical response to treatment with infliximab and pretreatment CRP levels. This study indicates that patients with high pretreatment CRP levels might benefit from higher dosages of infliximab or shorter dosing intervals.     

Polymyositis associated with infliximab treatment for rheumatoid arthritis

SIR, Treatment of rheumatoid arthritis (RA) with the chimericanti-tumour necrosis factor (TNF-) monoclonal antibody infliximabhas been proven efficacious and well tolerated [1, 2]. However,there are concerns about the safety of such treatment, withreports about induction of autoimmune phenomena [anti-double-strandedDNA (dsDNA) antibodies] and, rarely, development of systemiclupus erythematosus [3–5]. We describe a patient withRA who developed polymyositis following treatment with infliximab. A 52-yr-old woman presented in January 2001 with     

Treatment outcome of spondyloarthropathy with infliximab

The spondyloarthropathies (SpA) are a heterogenous group of diseases associated with axial and peripheral arthritis, enthesitis, inflammatory bowel disorders, presence of HLA B27 antigen and often with iridocyclitis. The aim of our study was to assess the efficacy of infliximab (chimeric monoclonal IgG 1 anti-TNF-alpha antibody) in the treatment of three patients with SpA. In two male patients (45- and 50-year old) psoriatic arthritis was diagnosed 28 and 22 years ago, and in 22-year old man ankylosing spondylitis was found before eight years. In all three cases dramatic response, almost complete resolution of joint manifestations and in patients with psoriatic arthritis regression of skin eruptions typical for psoriasis after one or two infusions was observed. In our opinion, the most optimal schedule of infliximab infusions was administration of the drug at weeks 0, 2, 6 and then every six weeks for at least 12 months. Discontinuation of therapy is associated with recurrence of symptoms of joint inflammation and increase in skin eruptions in patients with psoriatic arthritis within a few months.     

Treatment of refractory psoriatic arthritis with infliximab: a 12 month observational study of 16 patients

OBJECTIVE: To evaluate the effectiveness and toxicity of infliximab in patients with recalcitrant psoriatic arthritis (PsA). METHODS: Patients with treatment resistant PsA and at least six actively inflamed joints, who had failed to respond to at least two disease modifying agents, were included. Infliximab (5 mg/kg) was given at weeks 0, 2, 6, and every 6-8 weeks pending response. Clinical and laboratory measures included actively inflamed joint count (AJC), swollen joint count (SJC), psoriasis severity (PASI), HAQ, and SF-36. Response was defined as at least a 30% reduction in AJC and PASI. Differences from baseline were analysed using the signed rank test. RESULTS: Sixteen patients (12 male, 4 female), mean age 48 and disease duration 14 years, were included. At baseline the mean AJC was 22.5 and mean PASI 4.5. Eleven patients continued receiving methotrexate. The AJC did not show a statistically significant response. SJC improved significantly at week 54 (p = 0.01). The PASI improved significantly at weeks 14 (p = 0.001) and 30 (p = 0.002) and CRP was reduced significantly at week 30 (p = 0.02). The HAQ score improved at week 30 (p = 0.02). Six patients became positive for dsDNA without clinical features of a connective tissue disease. Six patients discontinued treatment owing to lack of efficacy (1) and toxicity (5). Other serious adverse events included: urticaria (3); thrombocytopenia (1); lower gastrointestinal bleeding (2); severe diarrhoea (2); serious infections (6). Raised transaminases, at least 1.5x normal, occurred in four patients. CONCLUSION: In refractory PsA, infliximab led to a marked improvement in psoriasis but modest response in joint disease. Toxicity and rate of treatment termination was high.     

Double-blinded infliximab dose escalation in patients with rheumatoid arthritis

OBJECTIVE: To determine the efficacy, safety and pharmacokinetics of infliximab dose escalation in patients with rheumatoid arthritis (RA) who had an inadequate response to 3 mg/kg infliximab treatment or whose disease flared after initially responding. METHODS: Patients with active RA, despite receiving methotrexate, received infliximab 3 mg/kg at weeks 0, 2, 6 and 14 in one of the three arms of the START trial. Beginning at week 22, patients had their infliximab dose increased in a double-blind fashion in increments of 1.5 mg/kg if the total tender and swollen joint count did not improve by at least 20% from baseline (lack of response) or the improvement at week 22 or later worsened by 50% or more (criterion for flare). RESULTS: Of the 329 evaluable patients, 100 (30.4%) patients required dose escalation at or after week 22 because of flare or lack of response. The majority of patients (>80%) who received up to three dose escalations showed >/=20% improvement in the total tender and swollen joint count after their last dose escalation. Patients who required dose escalations generally had lower preinfusion serum infliximab concentrations than those who did not require them. The incidences of adverse events and serious adverse events for the patients who received dose escalation(s) were similar to those of patients who did not receive dose escalation. CONCLUSION: Fewer than one-third of patients required a dose escalation. The majority of patients showed improvement after receiving increased doses of infliximab, without an increased risk of adverse events.     

Drug-induced lupus following treatment with infliximab in rheumatoid arthritis

After introduction of infliximab for the treatment of rheumatoid arthritis (RA), there have been many reports of patients developing asymptomatic higher rate of antinuclear antibodies and anti-dsDNA antibodies than in non-infliximab-treated patients. However, only five clinical drug-induced lupus (DIL) cases have been documented following treatment with infliximab, in RA and in Crohn's diseases. We report a case of a 69-year-old female with a 5 year history of RA, whowas successfully treated with low-dose methotrexate (MTX) and infliximab (initially 3 mg/kg and from the fourth infusion 5 mg/kg) for 23 weeks. Before the sixth infusion, she was diagnosed with DIL by both clinical features (fever > 38 degrees C, recurrence of active synovitis, myalgia, erythematous rash and general malaise) and laboratory findings (antinuclear antibodies 1:160, anti-double-stranded DNA positive by ELISA assay, decreased serum complement C3 andC4, hypergammaglobulinaemia, increased erythrocyte sedimentation rate). After discontinuation of treatment and therapy with oral prednisone, lupus resolved within 8 weeks.