Outcome of transition phase patients with juvenile idiopathic arthritis.

OBJECTIVES: Across diagnosis groups, successful transition of adolescent and young adults from children's hospitals to adult care is often associated with decreased treatment adherence and treatment results. The aim of this study was to characterize disease activity and anti-rheumatic medications following transfer of care of juvenile idiopathic arthritis (JIA) patients to the adult clinic. METHOD: All consecutive JIA patients aged 16-20 years who visited the specific transition clinic in the rheumatology outpatient clinic of Helsinki University Hospital between November 2012 and May 2013 and between April 2015 and April 2016 were evaluated. RESULTS: A total of 214 patients were identified, and 23 appeared in both cohorts. Females had higher disease activity scores (DAS) than males (DAS28-CRP 1.9 ± 0.7 versus 1.6 ± 0.3, p = .019; and DAS44-CRP 1.0 ± 0.7 versus 0.7 ± 0.5, p = .005; respectively) in the latter cohort. Disease-modifying antirheumatic drugs (DMARDs) were prescribed to 86% of patients, and 48% were on biological DMARDs (bDMARDs), whereas 14% had no specific treatments. CONCLUSION: Disease activity and clinic attendance remained stable during the transition period. The proportion of transition phase JIA patients on bDMARDs was high and disease activity was low. Reasons for lower disease activity in males in the latter cohort require further investigation.

Modeled Health Economic Impact of a Hypothetical Certolizumab Pegol Risk-Sharing Scheme for Patients with Moderate-to-Severe Rheumatoid Arthritis in Finland.

PURPOSE: To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-naïve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland. METHODS: A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015-2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index. RESULTS: In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of €7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix. CONCLUSION: The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients. FUNDING: UCB Pharma.

Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial.

OBJECTIVE: YKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission. METHODS: Ninety-nine patients with early DMARD-naïve RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay. RESULTS: At the baseline, plasma YKL-40 concentration was 57 ± 37 (mean ± SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-α antagonist infliximab was added on the combination treatment. CONCLUSIONS: High YKL-40 levels were found to be associated with disease activity in early DMARD-naïve RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission.

Synovial fluid detection in intra-articular injections using a bioimpedance probe (BIP) needle-a clinical study.

Intra-articular glucocorticoid injections are the recommended treatment for active arthritis, but accurate positioning of the needle may be challenging. Inexperienced physicians might decide not to inject because an unsuccessful injection impairs clinical outcome and may lead to complications; however, choosing not to inject may impair or delay the best possible treatment. Here, we address this problem by introducing a novel Bioimpedance Probe (BIP) Needle-guidance method that was tested in a clinical study. The BIP Needle was utilized for detection of synovial fluid. It measures real-time bioimpedance spectra and identifies when the needle tip is in contact with the synovial fluid. Injections into 80 joints with active arthritis were performed by an experienced rheumatologist using the BIP Needle. The location of the BIP Needle was ensured by aspiration of synovial fluid, absence of resistance during injection, and/or using real-time ultrasound imaging. Sensitivity and specificity of the device for synovial fluid detection were 86 % (CI 75-93 %) and 85 % (CI 74-92 %), respectively. The BIP Needles showed high spatial resolution and differentiated the synovial fluid from the surrounding tissues. However, lack of synovial fluid, anatomic variability, and intra-articular structures challenged the technology. The BIP Needles provided adequate results in intra-articular injections. Performance of the device was good even in small joints, which may be the most difficult for inexperienced physicians. Further performance improvement can be expected when more data is collected for mathematical models. Overall, this novel method showed potential to be used in real-time needle guidance.

[Interruption of biological drugs in patients affected with inflammatory diseases]. / Biologisten lääkkeiden tauotus tulehduksellisia tauteja sairastavilla.

The use of biological drugs in the treatment of inflammatory rheumatic diseases, bowel diseases, and psoriasis has increased. Patients receiving a biological drug are invariably under the supervision of a specialized physician, but many are also attending basic healthcare clinics. Every physician taking care of a patient receiving a biological drug should be aware of the principles of interruption. In the present article we will focus on common situations, where an interruption of a biological drug must be considered in the treatment of these inflammatory diseases.

[Systemic sclerosis]. / Systeeminen skleroosi.

Systemic sclerosis (scleroderma) is a rare connective tissue disease characterized by vasculopathy and immune dysfunction, leading to fibrosis with damage of multiple organs. Two major clinical subtypes are the diffuse and limited forms. The combination of Raynaud's phenomenon, puffy fingers and positive antinuclear antibodies are red flag features that should alert the clinician to the presence of very early systemic sclerosis, which can be treated with vasodilator, antithrombotic, and immunosuppressive drugs. Progress has been made even in the management of the most severe manifestations, including interstitial lung disease, pulmonary artery hypertension and scleroderma renal crisis.

[Imaging of inflammatory back pain]. / Tulehduksellisen selkäkivun kuvantamis- diagnostiikka.

We recommend magnetic resonance imaging of the sacroiliac joints as the first line imaging method in suspected inflammatory back disorder. Plain X-ray can be taken from those over 35 years of age. A nonconclusive finding in plain X-ray should be verified by MR imaging. For the present, diagnostic criteria for spondylarthritis do not take into account spinal changes. Typical spinal findings can, however, be helpful in making treatment decisions. In case the spinal region MR imaging should be utilized if possible, because radiography is particularly insensitive for thoracic spine. After a confirmed diagnosis, the inflammatory nature of the condition can usually be assessed clinically.

Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study).

OBJECTIVE: Early treatment of patients with rheumatoid arthritis (RA) with combination treatment starting with methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (FIN-RACo strategy) is superior to monotherapy. A study was undertaken to determine whether infliximab (INFL) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome. METHODS: 99 patients with early untreated active RA were enrolled in an investigator-initiated, randomised, double-blind, multicentre, parallel-group trial. Primary outcomes were remission and radiological changes at 2 years. All patients started with FIN-RACo. In addition, they were randomised to receive INFL or placebo (Pla) from weeks 4 to 26. RESULTS: At 24 months, 66% and 53%, respectively, of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology (ACR) criteria (p=0.19), 26% and 10% were in sustained modified ACR remission (p=0.042) and 82% in both groups were in remission by 28-joint disease activity score (not significant). Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4, respectively (p=0.0058). CONCLUSIONS: Most patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen. Adding INFL for the first 6 months delays radiological progression.

The good initial response to therapy with a combination of traditional disease-modifying antirheumatic drugs is sustained over time: the eleven-year results of the Finnish rheumatoid arthritis combination therapy trial.

OBJECTIVE: To evaluate the evolution of functional and clinical outcomes over 11 years in patients with early rheumatoid arthritis (RA) initially treated with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD. METHODS: A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the drug treatment strategy became unrestricted, but still targeted remission. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and clinical outcomes were assessed with the modified Minimal Disease Activity (MDA) measure and the American College of Rheumatology (ACR) criteria for remission. RESULTS: At 11 years, 138 patients were assessed (68 in the combination-DMARD group and 70 in the single-DMARD group). The mean+/-SD HAQ scores were 0.34+/-0.54 in the combination-DMARD group and 0.38+/-0.58 in the single-DMARD group (P=0.88). Modified MDA was achieved by 63% (95% confidence interval [95% CI] 51, 77) and by 43% (95% CI 32, 55) (P=0.016) of the combination-DMARD group and the single-DMARD group, respectively, and ACR remission by 37% (95% CI 26, 49) and by 19% (95% CI 11, 29) (P=0.017), respectively. CONCLUSION: Initial therapy with a combination of DMARDs in early RA results in higher rates of patients achieving modified MDA and strict ACR remission even over the long term than initial single-DMARD therapy. Targeting remission with tight clinical controls results in good functional and clinical outcomes in most RA patients.

Anti-TNF therapy in the treatment of ankylosing spondylitis: the Finnish experience.

Biological therapy for ankylosing spondylitis (AS) has led to improved disease control beyond that of conventional treatments. International recommendations encourage clinicians prescribing biological treatments to register patients in national registers to collect information on outcome and toxicity. Patients with AS (n = 229) from the Register of Biological Treatment in Finland (ROB-FIN) with severe disease of long duration were followed-up for up to 24 months. Due to an active disease, one or more concomitant disease-modifying antirheumatic drugs (DMARDs) were used by 86% at commencement of biological therapy. This add-on strategy with infliximab led to a rapid pain relief and improvement of patient's and physician's global assessments, C-reactive protein/erythrocyte sedimentation rate, and swollen and tender joint counts within 6 weeks. Concomitant use of NSAID and oral corticosteroid was reduced. Corresponding results were documented at 3 months with etanercept, which was more recently approved for the treatment of spondyloarthropathies. Seventy-nine percent of the patients were ASAS 20 responders. A subgroup of AS patients with only axial involvement (n = 46) responded correspondingly. The first biological drug was discontinued in only 7% due to lack of efficacy and in 6% due to adverse events. Anti-TNF agents, often used in combination with DMARDs, appeared to have persistent effectiveness and limited toxicity in a real-life clinical setting in a cohort of Finnish AS patients with severe disease and long disease duration.

Effectiveness of anakinra in rheumatic disease in patients naive to biological drugs or previously on TNF blocking drugs: an observational study.

The aim of this study was to evaluate the effectiveness of IL-1 inhibition in rheumatic disease using real-life, observational methods. We analyzed data from 47 patients collected from the national ROB-FIN for rheumatic disease. Commonly used, validated measures of efficacy and adverse effects were documented and analyzed. The series contains 47/1,135 patients (mean age 47+/-11 years, range 25-73, females 83%) on anakinra of whom 39 patients suffered from rheumatoid arthritis (RA), two presented with psoriatic arthritis, and four with juvenile RA. At 3 months (26/40), 46% reached American College of Rheumatology (ACR) 20 and 27% ACR 50. In patients naive to biological drugs, the response rate at 3 months was 60% for ACR 20 and 20% for ACR 50. At follow-up of the total series, ACR responses at 6 and 12 months were 69/56% for ACR 20 and 23/22% for ACR 50. These data give room for IL-1 suppression when treating patient with rheumatic disease. Careful selection of patients, together with combining anakinra with disease-modifying antirheumatic drugs, perhaps adds effectiveness. For treating clinicians in Finland, these results are encouraging, as reimbursed treatment alternatives for patients refractory to all other therapies are still few.

Cervical spine surgery in patients with rheumatoid arthritis: longterm mortality and its determinants.

OBJECTIVE: Atlantoaxial subluxation (AAS) is a frequent manifestation of rheumatoid arthritis (RA). The instability of the craniocervical junction caused by AAS is a potentially fatal condition and may require surgical treatment. Systemic manifestations associated with RA may increase the risk of perioperative complications. We evaluated the longterm mortality and its determinants in RA patients with AAS after cervical spine surgery. METHODS: A retrospective study of consecutive patients treated at Kuopio University Hospital between 1994 and 1998. Preoperative risk factors, neurological impairment using the Ranawat classification, perioperative course, functional outcome, and survival status were evaluated. RESULTS: During the study period 86 rheumatoid patients with AAS underwent cervical spine surgery. The mean followup time was 7.5 years (range 5.0-9.8). During the followup, 32 patients (37%) died. The mean survival time after surgery was 7.2 years (95% CI 6.7-8.0). Seven patients experienced postoperative complications. Age, AAS other than horizontal, and occurrence of complications were independent predictors of mortality. In two-thirds of the patients there was relief or decrease of pain, and the functional capacity improved. Neurological deficits subsided in 53% of cases. CONCLUSION: Patients with RA should be actively studied for AAS or other cervical instability, even when cervical symptoms are minor. Attention should be paid to perioperative management of these patients. Surgical treatment may not decrease the mortality of patients with RA, but it may result in more symptom-free life-years.

Stem cell transplantation in autoimmune diseases: an update.

Immunosuppressive or immunomodulatory treatments are often used in patients with various autoimmune diseases (AID). However, since conventional treatments are rarely curative, alternative treatment methods have been looked for. Based on animal experiments and anecdotal case reports, stem cell transplantation (SCT) has received considerable attention in the treatment of severe autoimmune diseases during the last decade. This review summarizes current experience of SCT in patients this field. Although early experience shows some promise, randomized studies are necessary to evaluate the real value of autologous SCT in various autoimmune diseases. Since autologous SCT may not be curative in patients with AID, also evaluation of allogeneic SCT is important in the future.

Total incidence and distribution of inflammatory joint diseases in a defined population: results from the Kuopio 2000 arthritis survey.

OBJECTIVE: To study the incidence of inflammatory joint diseases in a defined population in Finland. METHODS: We collected data for the year 2000 on a population of 87,000 inhabitants of Kuopio, Finland, of whom 20% were < 16 years of age. Information about the study was given through a local newspaper, and subjects attended one health center and 2 local hospitals for study. Inclusion criteria were that subjects have at least one peripheral joint with synovitis or signs of inflammation in sacroiliac, glenohumeral, or hip joints on the first visit. Incidence rates were calculated according to the diagnosis on the first visit, except for children, for whom diagnoses were established after 3 months' followup. RESULTS: A total of 188 adult incident cases (138 women, 50 men) and 11 children (8 girls, 3 boys) satisfied the inclusion criteria. The incidence of all arthritides was 230/100,000 (95% confidence interval 198.9-263.9) for the whole population; 271/100,000 (95% CI 233.7-312.7) for adults and 64/100,000 (95% CI 31.7-113.8) for children. Among adults the annual incidence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), other spondyloarthropathies (SpA), connective tissue disease (CTD), crystalline arthritis, viral arthritis, and undifferentiated arthritis were 36, 7, 23, 10, 13, 9, 19, 7, and 149/100,000, respectively. The mean age at diagnosis was 49.4 +/- 16.3 years for all cases of arthritis among adults, about the same for both women and men. The mean age at diagnosis was 59.7 years in RA, 31.5 years in AS, 48.7 years in PsA, 38.0 years in ReA, 36.5 years in other SpA, 36.1 years in CTD, 65.0 years in crystalline arthritis, 53.3 years in viral arthritis, and 48.3 years in undifferentiated arthritis. Four of 11 children had juvenile idiopathic arthritis (JIA). The incidence of JIA was 23/100,000 in the population < 16 years of age. Of the remaining cases, 3 children had antibodies against Sindbis (Pogosta) virus and 4 had a transient monoarthritis. CONCLUSION: The overall incidence of arthritides among adults was slightly higher than previously reported from Finland. The incidence rates in the child population are in agreement with previous figures. These data are useful in planning the provision of health care.

Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis.

OBJECTIVE: To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA). METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years. RESULTS: The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [approximately 42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission. CONCLUSION: The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA.