Decreasing muscle performance associated with increasing disease activity in patients with rheumatoid arthritis

Objectives Increasing evidence suggests that inflammation has a detrimental effect on muscle strength. Our objective was to analyse the association between muscle performance and different disease activity levels in patients with rheumatoid arthritis (RA). Method A total of 199 consecutive outpatients were subject to cross-sectional assessment. Measurements of grip strength, endurance of the upper and lower limbs and trunk strength were combined as a muscle performance composite score (MPCS), using a standardised method. The disease activity for 28 joints (DAS28), radiographs of small joints (Larsen score), rheumatoid factor, body mass index (BMI), comorbidities and anti-rheumatic drugs were verified. Patients questionnaires included sociodemographic information, pain level, global disease activity, the Beck Depression Inventory, the mental and physical component scores of Short Form-36 and physical activity level. Results Of the 199 patients, 36%, 17% and 47% patients had remission, low/moderate and high DAS28, respectively. The patients in remission had significantly shorter disease duration, better parameters in terms of pain, physicians assessment, Larsen, Beck or physical component score of Short Form-36, and they were more physically active than other patients. After adjustments for age, sex, RA duration, radiographs and BMI, the decreasing MPCS associated linearly with the increasing DAS28 activity levels (linearity, P Conclusion Poorer MPCS is clearly associated with higher disease activity in patients with RA. Muscle performance is a modifiable risk factor. The findings suggest evaluating muscle performance in clinical practice as a part of patient care.Peer reviewe

Effectiveness and drug survival of TNF-inhibitors in the treatment of psoriatic arthritis : A prospective cohort study

Background and objectives: Tumor necrosis factor (TNF)-inhibitors are used to treat psoriatic arthritis (PsA), but only a limited number of observational studies on this subject have been published thus far. The aim of this research was to analyze the effectiveness and drug survival of TNF-inhibitors in the treatment of PsA. Methods: PsA patients identified from the National Register for Biologic Treatment in Finland (ROB-FIN) starting their first, second, or third TNF-inhibitor treatment between 2004 and 2014 were included. Effectiveness was measured using ACR and EULAR response criteria and modeled using ordinal logistic regression. Treatment persistence was analyzed using Kaplan-Meier survival analysis and Cox proportional hazards model. Results: The study comprised 765 patients and 990 TNF-inhibitor treatment courses. EULAR moderate treatment responses at 6 months were achieved by 68% and 37% of the users of the first and the second or the third biologic, respectively. The probabilities of discontinuing the treatment within 12 and 24 months were 20% and 28%, respectively. Adjusted treatment responses to all TNF-inhibitors were similar; however, co-therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was not associated with better effectiveness. Adalimumab [hazard ratio (HR) = 0.62; 95% confidence interval (CD: 0.44-0.88] was superior to infliximab in drug survival while etanercept (HR = 0.77, 95% CI: 0.55-1.1) and golimumab (HR = 0.75, 95% CI: 0.46-1.2) did not differ from it. Co-medication with csDMARDs did not statistically improve drug survival. Conclusion: All available TNF-inhibitors showed similar treatment responses with or without csDMARDs. Adalimumab was associated with better drug survival when compared to infliximab. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

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-naive 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-alpha antagonist infliximab was added on the combination treatment. Conclusions High YKL-40 levels were found to be associated with disease activity in early DMARD-naive 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.Peer reviewe

Health-related quality of life and functional ability as patient-reported outcomes in rheumatoid arthritis:a study from two Finnish hospital-based populations

Abstract Reduced physical function and persistent pain are serious consequences of rheumatoid arthritis (RA). Clinical trials have shown that patients with RA suffer from a poor health-related quality of life (HR-QoL). However, limited information is available on the HR-QoL of patients treated in normal clinical practice. The purpose of the present study was to obtain information of how RA can influence on the patients´ HR-QoL and functional ability in a clinical setting and to investigate the impact of disease-related and demographic factors on the HR-QoL. The theoretical framework of the study was the biopsychosocial concept of health, i.e. the ICF model (International Classification of Functioning, Disability and Health) endorsed by WHO. HR-QoL was measured by the Nottingham Health Profile (NHP) questionnaire and functional ability by the Health Assessment Questionnaire (HAQ). The contents of these instruments and the NHP results were evaluated also within the ICF categories. The study consisted of a cross-sectional series and a longitudinal cohort carried out in two central hospitals in Finland in the late 1990s. The cross-sectional group of 122 consecutive out-patients had a mean disease duration of 11 years. The HR-QoL values of the patients were compared with those of an age and gender matched ”healthy” control group living in the same area. The HR-QoL values of the patients were examined also at different functional ability levels. The longitudinal group of 62 consecutive patients had symptom duration ≤ 24 months and no prior use of antirheumatic drugs or glucocorticosteroids at inclusion. First, the impact of the treatment response assessed by the EULAR (DAS28) criteria on HR-QoL was examined at six months from disease onset. Secondly, the HR-QoL changes and their associations with age and gender and with the changes in disease activity, radiographic assessments of hands and feet and functional ability were examined for ten years after the onset of RA. RA patients had poorer scores than the controls in the NHP in the dimensions measuring mobility, pain and energy. These dimensions, along with sleep, displayed also a significant linear association with poorer HAQ levels (p < 0.001). A better treatment response during the first six months was linearly associated with better HR-QoL with respect to the pain, energy and mobility dimensions (p < 0.001). Those patients exhibiting no response to treatment had already at baseline the poorest HR-QoL in the dimension for pain and emotional reaction compared with those in the moderate and good responders. During the ten years´ follow-up, all NHP dimensions except social isolation displayed significant improvements, these being most marked during the first six months. Changes in disease activity correlated with changes in pain, energy and emotional reaction (p < 0.001). The mean level of the HAQ was well preserved over the ten years of this study and its changes were correlated with changes in pain, mobility and energy (p < 0.001). Women had somewhat poorer NHP improvements in the dimensions assessing energy, emotional reaction and social isolation than males. Disease duration associated strongly with poorer mobility and pain dimensions (p < 0.01). Within the ICF framework, pain, mobility, energy and sleep were identified as being the most important categories from the patient's perspective. The results of the present study demonstrate that RA has a major influence on the patients´ HR-QoL but early and active treatment can improve the situation. In the ICF framework, the NHP covers a broader spectrum of the ICF categories than can be assessed by the HAQ.Tiivistelmä Alentunut fyysinen toimintakyky ja jatkuva kipu ovat nivelreumaan liittyviä vakavia seurannaisvaikutuksia. Kliiniset tutkimukset ovat osoittaneet, että nivelreumaa sairastavat potilaat kärsivät huonontuneesta terveyteen liittyvästä elämänlaadusta. Normaalista kliinisestä käytännöstä saatava tieto potilaiden terveyteen liittyvästä elämänlaadusta on kuitenkin niukkaa. Tämän tutkimuksen tarkoituksena oli saada tietoa nivelreuman vaikutuksista potilaiden terveyteen liittyvään elämänlaatuun ja toimintakykyyn kliinisessä asetelmassa ja tutkia sekä tautiin liittyvien että demografisten tekijöiden vaikutusta terveyteen liittyvään elämänlaatuun. Tutkimuksen teoreettisena viitekehyksenä käytettiin WHO:n hyväksymää toimintakyvyn, toimintarajoitteiden ja terveyden kansainvälistä luokitusta (ICF-malli). Terveyteen liittyvää elämänlaatua arvioitiin mittarilla Nottingham Health Profile (NHP) ja toimintakykyä mittarilla Health Assessment Questionnaire (HAQ). Kyseisten mittareiden sisältö samoin kuin NHP- tuloksia arvioitiin käyttämällä myös ICF- luokitusta. Tutkimus käsitti poikkileikkaus- ja pitkittäistutkimuksen, jotka toteutettiin 1990-luvun lopulla kahdessa suomalaisessa keskussairaalassa. Poikkileikkaustutkimukseen osallistui 122 perättäistä polikliinistä potilasta, joilla taudin kesto oli ollut keskimäärin 11 vuotta. Potilaiden terveyteen liittyvää elämänlaatua verrattiin samalla seudulla elävään iän ja sukupuolen suhteen kaltaistettuun verrokkiryhmään. Potilaiden terveyteen liittyvää elämänlaatua arvioitiin myös eri toimintakykytasoilla. Pitkittäistutkimus käsitti 62 perättäistä potilasta, joilla oireet olivat kestäneet ≤ 24 kuukautta ja jotka tutkimuksen alkaessa eivät olleet käyttäneet edeltävästi antireumaatteja tai kortikosteroideja. Näillä potilailla hoitovasteen vaikutusta terveyteen liittyvään elämänlaatuun arvioitiin EULAR DAS28- kriteerein kuuden kuukauden kohdalla taudin alusta. Lisäksi tutkittiin terveyteen liittyvän elämänlaadun muutoksia kymmenen vuoden ajalta nivelreuman alusta ja näiden muutosten yhteyttä ikään ja sukupuoleen, taudin aktiviteetissa ja käsissä ja jalkaterissä todettuihin röntgenmuutoksiin samoin kuin toimintakyvyn muutoksiin. Hoitovasteetta jääneillä potilailla oli jo lähtötilanteessa huonoin terveyteen liittyvä elämänlaatu kipu- ja tunnereaktiot- ulottuvuuksissa verrattuna kohtalaisen ja hyvän hoitovasteen saaneisiin. Kymmenen vuoden seurannassa kaikki NHP- ulottuvuudet sosiaalista eristyneisyyttä lukuun ottamatta osoittivat merkittävää paranemista. Selvintä se oli ensimmäisen kuuden kuukauden aikana. Taudin aktiviteetin muutokset korreloivat kipu-, tarmokkuus- ja tunnereaktiot- ulottuvuuksien muutoksiin (p <  0.001). Keskimääräinen HAQ- taso säilyi hyvänä kymmenen vuoden seurannassa ja HAQ- muutokset korreloivat kipu-, liikkuminen- ja tarmokkuus- ulottuvuuksien muutosten kanssa (p <  0.001). Naisilla oli miehiä jonkin verran huonompi NHP-paraneminen tarmokkuus-, tunnereaktiot- ja sosiaalinen eristyneisyys- ulottuvuuksissa. Taudin kesto oli selvästi yhteydessä huonompiin liikkuminen- ja kipu- ulottuvuuksiin (p <  0.01). ICF- luokitusta käytettäessä potilaiden näkökulmasta kipu, liikkuminen, tarmokkuus ja uni nousivat tärkeimmiksi kategorioiksi. Tämän tutkimuksen tulokset osoittavat, että nivelreumalla on huomattava vaikutus potilaiden terveyteen liittyvään elämänlaatuun, jota varhainen ja aktiivinen hoito voi kuitenkin parantaa. ICF- viitekehyksessä NHP kattaa laajemman spektrin ICF- luokista kuin HAQ

Demographics, RA-specific characteristics, comorbidities, lifestyle factors and health-related quality of life in patients with RA according to disease activity levels.

<p>Demographics, RA-specific characteristics, comorbidities, lifestyle factors and health-related quality of life in patients with RA according to disease activity levels.</p

Muscle performance measurements in patients with RA according to different disease activity levels.

<p>Muscle performance measurements in patients with RA according to different disease activity levels.</p

Adjusted (age, sex, RA duration, Larsen score and body mass index) muscle performance composity score according to remission, low/moderate and high DAS28 activity.

<p>Values are means with 95% confidence intervals.</p

YKL-40 was associated with disease activity and inflammation during intensive treatment with DMARDs.

<p>The figure shows quadratic relationships of YKL-40 with the disease activity measured as DAS28 (A) and with the inflammatory cytokine IL-6 (B) during the 26 weeks of treatment. The patients were treated for the first four weeks with a combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone, and thereafter randomized to receive either placebo infusions or infliximab infusions added to the treatment for another 22 weeks. Measurements were carried out at weeks 0, 4, 10, 18, and 26 during the treatment and area under the curve analysis over time (AUC_{0-26 weeks}) adjusted for age, gender and RF positivity was used. Gray-shaded areas represent 95% confidence intervals around the mean. YKL-40 AUC_{0-26 weeks} showed a statistically significant correlation to DAS28 AUC_{0-26 weeks} and IL-6 AUC_{0-26 weeks}.</p

CONSORT flow diagram for the NEO-RACo study.

<p>CONSORT flow diagram for the NEO-RACo study.</p

YKL-40 levels decreased during the intensive anti-rheumatic treatment with a combination of csDMARDs.

<p>The figure shows the mean change in plasma YKL-40 levels in 88 patients in the NEO-RACo -study treated with a combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone for the first four weeks, and thereafter randomized to receive either placebo infusions (Fin-RACo + Pla) or infliximab infusions (Fin-RACo + INFL) added on the csDMARD combination for another 22 weeks. YKL-40 levels decreased significantly (p<0.001) during the first four weeks of treatment with csDMARDs; when infliximab (or placebo) was added to the treatment there was a minor further decrease (groups combined, p = 0.031) but no difference between placebo and infliximab treatment groups was found. The change is presented as ng/ml, mean ± 95% CI, n = 88.</p