Infliximab therapy in pulmonary fibrosis associated with collagen vascular disease.

OBJECTIVE: To study the potential effectiveness of tumor necrosis factor a (TNF-alpha) inhibitor treatment for pulmonary fibrosis associated with a collagen vascular disease, CVD (rheumatoid arthritis, RA and systemic sclerosis, SSc) refractory to conventional treatment. METHODS: Four patients (three men with RA, one woman with SSc) were treated with infliximab. All patients received 3mg/kgr of infliximab at intervals 0, 2 and 6 weeks, and then maintenance infusions every 8 weeks afterwards for at least a 12-month period. Patients had active disease despite treatment with corticosteroids and other immunomodulatory agents. RESULTS: Treatment was well-tolerated from all patients. Pulmonary fibrosis remained stable during treatment in terms of symptoms, pulmonary function tests (PFTs) and High resolution computed tomography (HRCT) appearance. As expected, a clinical response was observed in joint symptoms in patients with RA as evaluated by the DAS28 (Disease Activity Score, the 28 joint version). CONCLUSION: This study suggests that inhibition of TNF-alpha with infliximab may stabilize the progression of pulmonary fibrosis associated with CVD. Prospective, controlled trials are necessary to determine the efficacy of infliximab in pulmonary fibrosis associated CVD.

Central nervous system involvement as the presenting manifestation of autoimmune rheumatic diseases: an observational study using the American College of Rheumatology nomenclature for neuropsychiatric lupus.

OBJECTIVE: We sought to describe CNS involvement as initial presentation of autoimmune rheumatic diseases using a standardized nomenclature. PATIENTS AND METHODS: A 6-year observational study (1999-2005) was conducted in the University Hospital of Heraklion Crete, a regional referral secondary/tertiary care academic center. Patients presenting with new neurological symptoms of acute/subacute onset underwent clinical and laboratory screening for systemic autoimmune disorders. The diagnosis of an autoimmune rheumatic disorder was based upon the American College of Rheumatology (ACR) classification criteria, whereas for primary antiphospholipid syndrome (PAPS) we used the Sapporo preliminary criteria. In order to describe the neurological syndromes we used the ACR nomenclature for neuropsychiatric lupus. RESULTS: During this period fourteen patients (ten females and four males) were recorded. Eight patients had systemic lupus erythematosus (SLE), four had primary APS and the remaining two had systemic vasculitis. Four out of the eight SLE patients had secondary APS. Two of them presented with movement disorder (chorea). The other two and all four patients with primary APS presented with cerebrovascular disease (CVD). These six patients comprised the 5.7% of young adults under < 45 years old with cerebrovascular accident admitted over the 6-year period. CONCLUSION: SLE and APS either primary or secondary to SLE were the most common underlying systemic autoimmune rheumatic diseases, in patients presenting with a neurological event of acute onset. Young adults (< 45 years old) with CVD should undertake screening for SLE/APS.

An open label, single dose study to evaluate the safety, efficacy, and effects on CD25 expression of ciclosporin in patients with active rheumatoid arthritis despite treatment with methotrexate and infliximab.

OBJECTIVE: To explore the safety, efficacy, and lymphocyte activation of a triple therapeutic regimen with infliximab, methotrexate (MTX), and ciclosporin A (CsA) by an open label, pilot study. PATIENTS AND METHODS: 19 patients (mean age 52.9 years) with active rheumatoid arthritis (mean DAS28 7.3) after a mean of 16.8 infliximab infusions and dose adjustments of both infliximab and MTX were enrolled. CsA was added to a stable therapeutic regimen. Disease activity was evaluated by the DAS28. Lymphocyte activation was evaluated by assessing CD25 expression on peripheral blood mononuclear cells (PBMCs). Primary end points were safety and efficacy according to the EULAR response criteria at 24 weeks. RESULTS: Eight patients (42%) discontinued treatment: adverse events (3), inefficacy (2) or non-compliance (2). One patient had a stroke and died. 5/11 (45%) patients who completed 24 weeks' treatment were moderate responders. CD25 expression, both on unstimulated and phytohaemagglutinin stimulated PBMCs in five patients assessed, was reduced (mean (SD) values from 37 (34)% to 15 (10)% and from 50 (15)% to 29 (20)%, respectively). CONCLUSION: In this group of patients with refractory, highly active disease, addition of CsA reduced lymphocyte activation, and resulted in a modest response and a high rate of discontinuation. In such patients, other new approaches need to be explored.

Low dose of infliximab is inadequate in most patients with spondylarthropathies.

OBJECTIVES: The recommended starting dose for infliximab for ankylosing spondylitis 5mg/kg is higher than that for rheumatoid arthritis. Because of the high expense of the drug lower doses may be considered. We report our experience with lower initial doses. METHODS: Thirty patients with active SpA (16 psoriatic arthritis, 12 ankylosing spondylitis and 2 undifferentiated) received 6 infliximab infusions. Patients had substantial axial disease (mean BASDAI at baseline 5.5). Concomitant therapy (methotrexate or prednisolone) remained stable throughout treatment period. The mean initial dose of infliximab was 3.5 mg/kg/infusion. Clinical efficacy was assessed by BASDAI. The criterion for dose adjustment was a BASDAI improvement of less than 50%. The primary end-points were the proportion of patients requiring a dose adjustment and the percentage of patients achieving 50% improvement in BASDAI after 6 infusions. RESULTS: In this cohort, 2 patients discontinued therapy, 1 for pulmonary infection and 1 for allergic reaction. Twelve patients (40%) showed 50% improvement in BASDAI between baseline and prior to the 7th infusion, while 15 patients (50%) had an improvement > 2 points. To achieve clinical response the frequency and/or the dose of infliximab infusions were increased in 63% of patients. The mean infliximab dose increased from 3.5 mg/kg at the first infusion to 4.3 mg/kg (p < 0.001) at the 7th infusion, resulting in a cumulative dose at the end of the study period comparable to the recommended one. CONCLUSIONS: In the majority of our SpA patients low starting doses of infliximab required subsequent adjustment. In these patients infliximab should be administered at the recommended dose of 5mg/kg/infusion.