Timo Yli-Kerttula

Whole-body distribution of 11C-choline and uptake in knee synovitis

C-choline PET imaging was performed on a 39-year-old female patient with seronegative oligoarthritis (duration of disease 23 years, human leucocyte antigen B27 positive, rheumatoid factor negative, erythrocyte sedimentation rate 17 mm/h, C-reactive protein 3 mg/l) using an Advance PET scanner (General Electric Medical Systems, Milwaukee, WI, USA) operated in 2D mode. The imaging field of view (FOV) in the axial direction is 152 mm. The patient was placed supine on a scanner couch, and the position of the inflamed knee joint in the centre of the FOV was secured by physical examination. Transmission scanning for atten-

Influence of triple disease modifying anti-rheumatic drug therapy on carotid artery inflammation in drug-naive patients with recent onset of rheumatoid arthritis

OBJECTIVE Increased atherosclerosis in RA is not fully explained by the ordinary risk factors, but it may be related to vascular inflammation. The aim of this study was to investigate the degree of carotid artery inflammation in drug-naive patients with early RA before and after DMARD triple therapy. METHODS Fifteen non-diabetic patients with recently diagnosed RA [age 51 (16) years, 6 males] were examined before and at 2 and 4 weeks after the initiation of combination therapy with MTX, SSZ, HCQ and ⩽10 mg/day oral prednisolone. Eight healthy males aged 49 (6) years were examined once as controls. Inflammation in the carotid artery was quantified, using [(18)F]fluorodeoxyglucose ((18)F-FDG)-PET/CT, as the maximum standardized uptake value (SUVmax) and the maximum target-to-background ratio (TBRmax). RESULTS Before the treatment, patients with RA had significantly higher carotid artery (18)F-FDG uptake, as compared with healthy controls [TBRmax 1.78 (0.07) vs 1.51 (0.08), P = 0.03]. The 4-week DMARD therapy reduced the TBRmax to the level of healthy controls [1.53 (0.05), P = 0.84]. Compared with the baseline, the TBRmax decreased by 12.4 (16.8)% (P = 0.01) during 4-week DMARD therapy. At baseline, the SUVmax correlated with ESR (r = 0.52, P = 0.02) and CRP (r = 0.65, P = 0.01). Change in SUVmax correlated with changes in ESR and CRP after 4 weeks of treatment, as did the changes in TBRmax and SUVmax with DAS at 12 weeks of treatment. CONCLUSION (18)F-FDG-PET/CT revealed that drug-naive patients with early RA show carotid artery inflammation that can be efficiently reduced by 1-month DMARD triple therapy.

Patient-reported outcomes as predictors of remission in early rheumatoid arthritis patients treated with tight control treat-to-target approach

Identifying prognostic factors for remission in early rheumatoid arthritis (ERA) patients is of key clinical importance. We studied patient-reported outcomes (PROs) as predictors of remission in a clinical trial. We randomized 99 untreated ERA patients to receive remission-targeted treatment with three disease-modifying antirheumatic drugs and prednisolone for 24 months, and infliximab or placebo for the initial 6 months. At baseline, we measured following PROs: eight Short Form 36 questionnaire (SF-36) dimensions, patient’s global assessment [PGA, visual analogue scale (VAS)], Health Assessment Questionnaire (HAQ), and pain VAS. We used multivariable-adjusted regression models to identify PROs that independently predicted modified American College of Rheumatology remission at 2 years. Follow-up data at 2 years were available for 93 patients (92%), and 58 patients (62%) were in remission. At baseline, patients who achieved remission had higher radiological score (p = 0.04), lower tender joint count (p = 0.001), lower PGA (p = 0.005) and physician’s global assessment (p = 0.019), lower HAQ (p = 0.016), less morning stiffness (p = 0.009), and significantly higher scores in seven out of eight SF-36 dimensions compared with patients who did not. In multivariable models that included all PROs, remission was associated with SF-36 dimensions higher vitality (odds ratio 2.01; 95% confidence interval 1.19–3.39) and better emotional role functioning (odds ratio 1.64; 95% confidence interval 1.01–2.68). PGA, pain VAS, HAQ, and other SF-36 dimensions were not associated with remission. We conclude that self-reported vitality and better emotional role functioning are among the most important PROs for the prediction of remission in ERA.

Early Targeted Combination Treatment with csDMARDs Sustains Excellent Long-term Outcomes in Rheumatoid Arthritis

OBJECTIVE The short-term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well-established, but the long-term success of such strategies is speculative, as is the role of early add-on biologics. We assessed the 10-year outcomes of patients with early RA treated with initial remission-targeted triple combination of conventional synthetic disease-modifying antirheumatic-drugs (csDMARDs), 7.5 mg prednisolone (PRD) and additional infliximab or placebo infusions. METHODS Ninety-nine patients with early, DMARD-naïve RA were treated with a triple combination of csDMARDs and PRD, and randomized to double-blindly receive either infliximab (FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions during the first 6 months. After 2 years, the treatment strategies became unrestricted, but the treatment goal was strict NEO-RACo remission. At 10 years, the clinical and radiographic outcomes and the drug treatments used between 5-10 years were assessed. RESULTS Ninety patients (91%) were followed after 2 years, 43 in the FIN-RACo+INFL and 47 in the FIN-RACo+PLA group. At 10 years, the respective proportions of patients in strict NEO-RACo and in DAS28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 46% and 38% (p=0.46), and 82% and 72% (p=0.29). The mean total Sharp van der Heijde score was 9.8 in the FIN-RACo+INFL and 7.3 in the FIN-RACo+PLA group (p=0.34). During the 10-year follow-up 26% of the FIN-RACo+INFL group and 30% of the FIN-RACo+PLA group patients had received biologics (p=0.74). CONCLUSION In early RA, excellent results can be maintained up till 10 years in most patients treated with initial combination csDMARDs and remission-targeted strategy, regardless of initial infliximab/placebo infusions. This article is protected by copyright. All rights reserved.The short‐term outcomes of remission‐targeted treatments of rheumatoid arthritis (RA) are well‐established, but the long‐term success of such strategies is speculative, as is the role of early add‐on biologics. We assessed the 10‐year outcomes of patients with early RA treated with initial remission‐targeted triple combination of conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs), 7.5‐mg prednisolone, and additional infliximab (IFX) or placebo infusions.

Reversible brain hypometabolism associated with central nervous system systemic lupus erythematosus

A 63-year-old woman with a history of hypothyroidism andrheumatoid arthritis was referred to the internal medicinedepartment due to progressive muscle fatigue, weight loss of15 kg, haemolytic anaemia, fever and memory impairment.The Mini-Mental State Examination was abnormal (MMSE16/30). The initial brain MRI showed general corticalatrophy and FDG PET suggested a neurodegenerativedisease with symmetrical severe hypometabolism in thefrontal, parietal and temporal cortexes. Neurological consul-tation did not lead to a specific diagnosis. Later antinuclearantibody serological tests were indicative of systemic lupuserythematosus (SLE) [1–5]. The patient was treated withhigh-dose corticosteroids and cyclophosphamide.After 18 months the brain scans were controlled. Anatom-ical and metabolic brain findings had normalized, confirmingthat the observed hypometabolism and atrophy were indeedrelated to brain manifestation of SLE and, importantly, couldbe reversed by efficient treatment. Cognitive performance onneuropsychological tests had also recovered. Automatedcomparison of the FDG PET images to a normal populationwiththe3D-SSPprogramshowsthedramatictreatmenteffectin z-score images of surface projections.

Antibiotics in the Treatment of Reactive Arthritis

Reactive arthritis is triggered by an infection. Much of evidence has been accumulated to prove that the causative microbes or their components may persist in the organism for extended periods, maintaining an active immune response. Therefore, the question about the value of antibiotics has been entertained by several research groups. A number of studies have demonstrated that antibiotics may be useful only if applied very early, before the pathogenetic process has started. In established reactive arthritis short-term treatment is apparently not effective. Also a three-month course of ciprofloxacin has been demonstrated to be without clinical effect as observed during a one-year follow-up. The same findings were made in a large multicenter EULAR study regarding azithromycin. However, when patients were re-examined four to seven years after an initial 3-month course of the antibiotics in the Finnish ciprofloxacin study, it turned out that patients in the placebo group had significantly more often developed chronic joint symptoms and objective findings of rheumatic disease than those treated with the antibiotic. In addition, a recent study suggests that intensive treatment with a combination of doxycycline and rifampin may have a beneficial effect even in chronic reactive arthritis. The question must be raised whether antibiotics, after all, should be considered especially in HLA-B27 positive patients.

Follow-up study of the effect of a three-month course of ciprofloxacin on the late prognosis of reactive arthritis

BACKGROUND The value of antibiotics in the treatment of reactive arthritis (ReA) is still controversial. OBJECTIVES To analyse the long term outcome of patients with ReA, treated with a three month course of ciprofloxacin or placebo. METHODS Patients who had had ReA and had participated in a double blind, placebo controlled trial on the effectiveness of ciprofloxacin 4-7 years earlier were invited to a clinical examination. Of the 71 patients who were included in the original study, 53 agreed to visit the clinic for an examination. Twenty six of 53 patients had originally received ciprofloxacin and 27 had belonged to the placebo group. Of these, 20 in the ciprofloxacin and 25 in the placebo group were HLA-B27 positive. RESULTS 11/27 (41%) patients in the original placebo group had now developed chronic rheumatic disease, as compared with only 2/26 (8%) patients originally treated with ciprofloxacin (p=0.006). Two patients who originally had received placebo, none in the ciprofloxacin group had developed ankylosing spondylitis, and three patients in the original placebo group, none in the ciprofloxacin group had recurrent anterior uveitis. The same tendency was seen when several different measures were analysed. Of the patients with chronic spondyloarthropathy, 10 in the placebo and none in the ciprofloxacin group were HLA-B27 positive. CONCLUSION Analysis 4-7 years after the initial ReA suggests that a three month course of antibiotics in the acute phase may have a beneficial effect on the long term prognosis.