Visa Honkanen

Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis

Objective: To evaluate the efficacy of anti-tumour necrosis factor (anti-TNF) treatment in juvenile idiopathic arthritis (JIA)-associated uveitis. Methods: 24 patients with uveitis taking etanercept and 21 taking infliximab were studied. The endpoint ophthalmological evaluation was at 24 months or at the termination of the first biological agent. The ocular inflammatory activity was graded on the basis of the number of anterior chamber cells. Results: Of the 45 patients, uveitis improved in 14 (31%), no change was observed in 14 (31%) and the activity of uveitis increased in 17 (38%). Inflammatory activity improved more frequently (pu200a=u200a0.047) in the patients taking infliximab than in those taking etanercept. The number of uveitis flares/year was higher (pu200a=u200a0.015) in the patients taking etanercept (mean 1.4, range 0–3.2) than in those taking infliximab (mean 0.7, range 0–2). Uveitis developed for the first time while taking anti-TNF treatment in five patients—4 taking etanercept (2.2/100 patient-years) and 1 taking infliximab (1.1/100 patient-years). Conclusions: During anti-TNF treatment, the ophthalmological condition improved in one-third of the patients with uveitis. In chronic anterior uveitis, associated with refractory JIA, infliximab may be more effective than etanercept.

Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed

In rheumatoid arthris s various pro-inflammatory metabolites of arachidonic acid (AA), such as leukotriene B4 (LTB4) and prostaglandin E2 (PGE2), contribute to tissue destruction and pain. In contrast to AA, which is an omega-6 fatty acid, the omega-3 fatty acids, after having been liberated from the cell membrane phospholipids, are further converted into the non-or anti-inflammatory eicosanoids LTB5 and PGI3. AA concentration is an important regulatory step in the synthesis of both prostanoids and leukotriens. Dietary supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has therefore been used to decrease the ratio of AA to EPA or DHA to obtain beneficial clinical effects. EPA and DHA are found in animal fat and are quite expensive compared to their precursor alpha-linolenic acid (alpha-LNA) found in flaxseed oil. We, therefore, performed a placebocontrolled trial with alpha-LNA in 22 patients with rheumatoid arthritis, using a linoleic acid preparation as a placebo. After a 3-month follow-up, the treatment group showed an increased bleeding time, but the clinical, subjective (global assessment, classification of functional status, joint score index, visual analogue scale, pain tendereness score) and laboratory parameters (haemoglobin, erythrocyte sedimentation rate, C-reactive protein) did not show any statistical alterations. AA, EPA and DHA did not change either in spite of a significant increase in alpha-LNA in the treatment group. Thus, 3-months supplementation with alpha-LNA did not prove to be beneficial in rheumatoid arthritis.

Impact of anti-TNF treatment on growth in severe juvenile idiopathic arthritis.

Objectives: To evaluate the impact of anti-tumour necrosis factor (TNF) treatment on growth and to identify the predictors for the change in growth in severe juvenile idiopathic arthritis (JIA). Methods: Data from 71 JIA patients (43 on etanercept, 28 on infliximab) were reviewed two years before and two years on the anti-TNF treatment. The patients had polyarticular disease course (48 polyarthritis, 19 extended oligoarthritis, two systemic arthritis, and two enthesitis related arthritis). At the initiation of the anti-TNF treatment, their mean age was 9.6 years and the mean duration of JIA, 5.7 years. Results: In the patients with delayed growth before anti-TNF treatment (nu200a=u200a53), the growth velocity, measured as the change in height standard deviation score, accelerated +0.45 (95% confidence interval, 0.33 to 0.56) (p<0.001) during the anti-TNF treatment. In the patients with normal or accelerated growth before anti-TNF treatment (nu200a=u200a18), the change in growth velocity was +0.05 (0.07 to 0.16) (pu200a=u200a0.39). At two years on anti-TNF treatment, the growth velocity between these two groups was similar. No difference was found between the patients treated with etanercept or infliximab. A decelerating growth rate before the anti-TNF treatment was the strongest predictor for the observed increase in the growth velocity. The change in the inflammatory activity remained a significant predictor of the growth velocity even after the decrease in glucocorticoid dose was taken into account. Conclusions: In the treatment of polyarticular JIA, the anti-TNF treatment not only suppresses inflammation but also restores growth velocity.

Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis

Objectives: To evaluate drug survival (continuation rates on drug) of anti-tumour necrosis factor (TNF) agents in juvenile idiopathic arthritis (JIA) and predictors for treatment discontinuation. Methods: A retrospective observational study on JIA patients taking etanercept (n u200a=u200a 105) or infliximab (n u200a=u200a 104) with at least one year follow-up. Kaplan–Meier curves and log-rank statistics were used to compare treatments and a proportional hazards model to assess risk factors for discontinuation. Results: Etanercept versus infliximab treatment survival at 12 months was 83% versus 80%, at 24 months 68% versus 68%, at 36 months 64% versus 53%, at 48 months 61% versus 48% (pu200a=u200a0.194), respectively. Reasons for discontinuing the first biological treatment were inefficacy (etanercept 28% vs infliximab 20%, pu200a=u200a0.445), adverse events (7% vs 22%, pu200a=u200a0.002) or inactive disease (10% vs 16%, pu200a=u200a0.068). Women (hazard ratio (HR) 2.8, 95% CI 1.3 to 5.8), patients with systemic JIA (HR 7.8, 95% CI 1.7 to 34.9) or those taking infliximab (HR 2.0, 95% CI 1.2 to 3.3) were at higher risk of treatment discontinuation. One-third of the patients were switched to the second anti-TNF therapy, which was discontinued less frequently than the first. At 12 months treatment survival of etanercept was 60%, infliximab 58% and adalimumab 66% as the second-line anti-TNF therapy. Conclusions: Although infliximab was discontinued more often than etanercept because of adverse events, during a 48-month follow-up the overall treatment survival of etanercept and infliximab as the first biological agent in JIA was comparable. A switch from one anti-TNF agent to another appears a reasonable therapeutic option.

Teaching of patients undergoing total hip replacement surgery

We studied the effect of patient teaching in 60 patients who underwent primary total hip replacement surgery. All the patients received an illustrated patient guide. In addition to the general patient teaching given by doctors, nurses and physiotherapists, a randomly chosen group of 27 patients received a session of intensified patient teaching. At the follow-up, 2-3 months postoperatively, 61% of patients thought that they had received the main part of their information from the physiotherapists, 9% from their doctors and 4% from the nursing staff. The importance of a well-illustrated guide was pointed out. The knowledge of potential complications, such as infection, remained poor; 37% could not name one single relevant complication. At the follow-up, the younger or better educated patients did not score any better. The experimental group who had received intensified teaching differed only slightly from the controls, but they knew significantly better when to inform their doctor of potential complications. Also, the experimental group showed greater interest in obtaining more information about their replaced hip. Patients in the experimental group showed significantly better adherence to the instructions for the postoperative rehabilitation programme.

Predictive clinical and laboratory parameters for serum zinc and copper in rheumatoid arthritis.

Zinc and copper have important effects on T cell mediated immunity and on neutrophil function, but it is not known how the causes or effects, of low serum zinc and high serum copper relate to the clinical picture of rheumatoid arthritis (RA). In this study serum zinc and copper determined by flame atomic absorption spectrometry and 30 other clinical, immunological, and laboratory parameters in 60 patients with RA were analysed by stepwise multiple linear regression analysis. Joint score index, rheumatoid factor titre, seropositivity, haemoglobin, and C reactive protein (CRP) were among the nine independent variables which together predicted 73% of the serum zinc variation. This suggests that there is an association between the immune-inflammatory rheumatoid process and the serum zinc concentration. CRP alone had only a 3% independent predicting value for serum zinc, however. This suggests that metallothionein mediated sequestration in the liver, induced by interleukin 1, is not an important explanatory factor in a cross sectional study of chronic inflammation. Furthermore, serum zinc did not have any predictive value at all for serum copper concentration. This does not support the hypothesis suggesting that serum zinc deficiency leads to high serum copper by inducing gastrointestinal metallothionein and high caeruloplasmin.

Serum trace elements in juvenile chronic arthritis.

SummaryWe evaluated the serum concentrations of zinc., copper and selenium in 125 patients with juvenile chronic arthritis (JCA). Trace element levels showed distinct abnormalities as compared with those of a large group of healthy children. Serum zinc and selenium concentrations were lower and those of copper higher in children with arthritis than in healthy children and, further, patients with polyarthritis had significantly higher copper and lower zinc levels than those with oligoarthritis. Serum zinc levels showed a direct correlation with hemoglobin and an inverse correlation with values for the erythrocyte sedimentation rate (ESR), whereas copper correlated directly with ESR. Selenium values did not correlate with the activity of the disease, but were low in the patients with arthritis of long duration.

Iron status during anti-TNF therapy in children with juvenile idiopathic arthritis

Patients with active juvenile idiopathic arthritis (JIA) have frequently low haemoglobin (Hgb) due to inflammation and/or iron deficiency. The aim of the study was to evaluate the effect of anti-tumor necrosis factor (TNF) therapy on their iron status. Twenty children with JIA were treated with either etanercept (nu2009=u20098) or infliximab (nu2009=u200912) for 12xa0months. Iron status was assessed during anti-TNF treatment by Hgb, mean corpuscular volume of red blood cells (MCV), serum iron (sFe), ferritin, percent transferrin saturation (sTrfesat) and serum transferrin receptor concentration (sTfR). The sTfR/log ferritin index (TfR/logF) was also used. Prior to the therapy, Hgb and MCV were 118u2009±u200915.5xa0g/L and 79u2009±u20097.7xa0fl in the infliximab group, and 113u2009±u200912.5xa0g/L and 78u2009±u20095.8xa0fl in the etanercept group, respectively. In the whole group of patients, sFe was 6.3u2009±u20094.1xa0μmol/L and sTrfesat was 9%u2009±u20096%. During anti-TNF therapy, Hgb and MCV improved significantly without use of iron supplementation, and sFe and sTrfesat increased from low to normal levels while inflammation markers decreased, except in one patient, in whom sTfR stayed elevated and the TfR/logF index value was high. In patients with active JIA associated with anaemia, low levels of sFe and sTrfesat cannot be used as markers for iron deficiency. In such patients, sTfR together with TfR/logF seem to be useful in assessing iron deficiency.

Revision of cemented hip arthroplasties: 101 hips followed for 5 (4–9) years

101 hips were revised with cemented Lubinus prostheses after failed primary cemented arthroplasty, and followed for 5 (4-9) years. Radiographically, 41 hips (36 femoral stems and 13 acetabular components) had become loose. The use of an intramedullary plug at the revision did not prevent sinking of the prosthesis. No difference was found between conventional or pressure-injection cementation techniques. In cases where the stem was inserted in varus or the acetabular component was in malposition there was increased loosening. Patients below 50 years of age had oftener more than 5 mm sinking of the stem and more prosthesis loosenings.

Total hip replacement after intertrochanteric osteotomy.

Forty-five hips were analyzed in 42 patients treated with total hip replacements (THR) after earlier intertrochanteric osteotomies. At time of osteotomy, the patients mean age was 50 years (range: 14 to 65). Total hip replacement was performed at a mean interval of 11.9 years later (standard deviation: 7.7). Narrowing or closure of the medullary canal made insertion of the prosthesis stem difficult in 10 cases. After THR, the patients were followed for a mean of 6 years (range: 3 to 11). At follow up, the hips had a mean Mayo score of 81 (SD = 13) points (17 excellent, 12 good, 7 fair, 9 poor). The failure rate was 6.7%. Being overweight had an adverse effect on outcome. Intertrochanteric osteotomy may impair results after subsequent THR.