Is the disease course of rheumatoid arthritis becoming milder? Time trends since 1985 in an inception cohort of early rheumatoid arthritis.

Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Arthritis & Rheumatology (Impact Factor: 7.87). 10/2005; 52(9):2616-24. DOI: 10.1002/art.21259
Source: PubMed

ABSTRACT Based on comparisons of short-term cohort studies or cross-sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years.
We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985-1990, 1990-1995, 1995-2000, 2000-2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts.
The DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease-modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy.
The course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy.

Download full-text


Available from: Jaap Fransen, Jan 13, 2014
  • Source
    • "RA is a chronic systemic autoimmune disease characterized by inflammatory polyarthritis which affects approximately 0.5 -1% of the population worldwide (Hochberg et al., 2007). Although the currently favored treatment regime using disease-modifying anti-rheumatic drugs (DMARD's) in an early stage of RA is believed to have a favorable result on disease course by influencing inflammation, patients assessment of disease activity and functional disability do not always support this result (Welsing et al., 2005). Even 30% of the RA patients initiating the most effective treatment option available, anti-TNFα therapy, fail to respond (Smolen, 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Metabolites play numerous roles in the healthy and diseased body, ranging from regulating physiological processes to providing building blocks for the body. Therefore, understanding the role of metabolites is important in elucidating the etiology and pathology of diseases and finding targets for new treatment options. Rheumatoid arthritis is a complex chronic disease for which new disease management strategies are needed. The aim of this review is to bring together and integrate information about the various roles that metabolites have in rheumatoid arthritis. An extensive PubMed search is conducted to collect the relevant manuscripts. The metabolites are discussed in relation to rheumatoid arthritis. Subsequently, the metabolites are organized according to levels of system organization. In the last section an integrated pathway analysis of the metabolites conducted with Ingenuity Pathway Analysis software is presented. Literature search resulted in information about vitamins, eicosanoids, fatty acids, lipids, hormones and peptides. The metabolites could be related to metabolic processes, oxidative stress processes and inflammatory processes. Cell death, lipid metabolism and small molecule biochemistry were found by the pathway analysis to be the top functions, characterized by the metabolites arachidonic acid, ascorbic acid, beta-carotene, cholecalciferol, hydrocortisone, keratan sulfate, melatonin, palmitic acid and stearic acid. These nine metabolites are highly connected to a number of canonical pathways related to immune functions, the production of nitric oxygen and reactive oxygen species in macrophages and pathways involved in arthritis. This review indicates groups of metabolites that could be interesting for metabolomics studies related to rheumatoid arthritis. Circadian rhythms of metabolite levels are found to be important for understanding and treating rheumatoid arthritis. In addition, some key processes and pathways are found by integrating the metabolite data. This might offer new ideas for studies into the mechanism of and possible treatment options for rheumatoid arthritis.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Seit Mitte der 1980er Jahre ist ein globaler Rückgang an operativen Eingriffen für Patienten mit rheumatoider Arthritis (RA) zu verzeichnen, sowohl für gelenkerhaltende Eingriffe wie Synovektomien als auch für Gelenkersatzoperationen. Die Ursachen hierfür liegen in einer früheren Erkennung der Erkrankung sowie vor allem der Verfügbarkeit effektiver medikamentöser Therapieoptionen. Der Artikel fasst im allgemeinen Teil die aktuelle Datenlage zu den rheumachirurgischen Eingriffen in der Ära der biologischen Therapieprinzipien zusammen. Der spezielle Teil diskutiert den Stellenwert der Synovektomie der großen Gelenke (Hüftgelenk, Kniegelenk, Schultergelenk) unter besonderer Berücksichtigung der Biologika-Therapie. Since the mid 1980s, a global decrease in surgical procedures related to rheumatoid arthritis (RA) has been documented for joint-preserving procedures such as synovectomy as well as joint replacement surgery. This reflects improvements in the early management of rheumatoid arthritis and availability of more effective medical treatment. The present review summarizes the recent literature on the frequency of orthopaedic surgery in RA patients as well as the role of synovectomy in the rheumatoid hip, knee and shoulder in times of biological RA therapy. SchlüsselwörterRheumatoide Arthritis–Synovektomie–Operation–Gelenk–Biologika KeywordsRheumatoid arthritis–Synovectomy–Surgery–Joint–Biologicals
    Zeitschrift für Rheumatologie 01/2011; 70(1):9-13. DOI:10.1007/s00393-010-0679-0 · 0.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) patients have premature mortality. Contrary to the general population, mortality in RA has not declined over time. This study aimed to evaluate determinants of mortality in RA by examining causes of death (CoDs) over time, accuracy of CoD diagnoses, and contribution of RA medication to CoDs. This study further evaluated detection rate of reactive systemic amyloid A amyloidosis, which is an important contributor to RA mortality. CoDs were examined in 960 RA patients between 1971 and 1991 (Study population A) and in 369 RA patients autopsied from 1952 to 1991, with non-RA patients serving as the reference cases (Study population B). In Study population B, CoDs by the clinician before autopsy were compared to those by the pathologist at autopsy to study accuracy of CoD diagnoses. In Study population B, autopsy tissue samples were re-examined systematically for amyloidosis (90% of patients) and clinical data for RA patients was studied from 1973. RA patients died most frequently of cardiovascular diseases (CVDs), infections, and RA. RA deaths declined over time. Coronary deaths showed no major change in Study population A, but, in Study population B, coronary deaths in RA patients increased from 1952 to 1991, while non-RA cases had a decrease in coronary deaths starting in the 1970s. Between CoD diagnoses by the clinician and those by the pathologist, RA patients had lower agreement than non-RA cases regarding cardiovascular (Kappa reliability measure: 0.31 vs. 0.51) and coronary deaths (0.33 vs. 0.46). Use of disease modifying anti-rheumatic drugs was not associated with any CoD. In RA patients, re-examination of autopsy tissue samples doubled the prevalence of amyloid compared with the original autopsy: from 18% to 30%. In the amyloid-positive RA patients, amyloidosis was diagnosed before autopsy in only 37%; and they had higher inflammatory levels and longer duration of RA than amyloid-negative RA patients. Of the RA patients with amyloid, only half had renal failure or proteinuria during lifetime. In RA, most important determinants of mortality were CVDs, RA, and infections. In RA patients, RA deaths decreased over time, but this was not true for coronary deaths. Coronary death being less accurately diagnosed in RA may indicate that coronary heart disease (CHD) often goes unrecognized during lifetime. Thus, active search for CHD and its effective treatment is important to reduce cardiovascular mortality. Reactive amyloidosis may often go undetected. In RA patients with proteinuria or renal failure, as well as with active and long-lasting RA, a systematic search for amyloid is important to enable early diagnosis and early enhancement of therapy. This is essential to prevent clinical manifestations of amyloidosis such as renal failure, which has a poor prognosis. Nivelreuma aiheuttaa nivelmuutoksia, mutta se myös lyhentää elinikää. Reumapotilaat kuolevat samoihin sairauksiin kuin väestö, mutta myös nivelreumaan. Vaikeassa reumassa toisinaan kehittyvä sekundaarinen amyloidoosi on tärkeä elinikää lyhentävä tekijä. Reumapotilaiden elinikä ei ole pidentynyt toisin kuin väestön keskimääräinen elinikä. Tämän väitöskirjatutkimuksen tavoitteena oli selvittää reumapotilaiden lisääntyneeseen kuolleisuuteen vaikuttavia tekijöitä tutkimalla reumapotilaiden kuolinsyitä pitkän ajanjakson aikana, kuolinsyydiagnoosien tarkkuutta, reumalääkityksen vaikutusta kuolinsyihin ja sitä kuinka kattavasti amyloidoosi oli diagnosoitu. Väitöskirjatyössä tutkittiin 960 reumapotilaan kuolinsyyt vuosilta 1971 - 1991 (aineisto A) ja 369 reumapotilaan ja verrokkien kuolinsyyt, jotka oli todettu ruumiinavauksessa vuosina 1952 - 1991 (aineisto B). Kuolinsyydiagnoosin osuvuutta tutkittiin vertaamalla ruumiinavauslähetteen oletettuja kuolinsyitä ruumiinavauksessa todettuihin kuolinsyihin (aineisto B). Ruumiinavauksessa otetut kudosnäytteet tutkittiin uudelleen 90%:lta potilaista amyloidoosin toteamiseksi ja sairaskertomustiedot kerättiin vuoden 1972 jälkeen kuolleilta reumapotilailta (aineisto B). Sydän- ja verisuonitaudit, reuma ja infektiot olivat reumapotilaiden tärkeimmät kuolinsyyt. Reuman aiheuttamat kuolemat vähenivät. Reumapotilaiden sepelvaltimotautikuolemat lisääntyivät 1952 - 1991 välillä. Verrokeilla ne kääntyivät laskuun 1970-luvulla (aineisto B). Reumapotilaiden sydän- ja verisuonitauti- ja sepelvaltimotautikuolemat olivat alidiagnosoituja. Reumalääkkeiden käyttö ei vaikuttanut kuolinsyihin. Amyloidoosi oli todettu elinaikana vain kolmasosalla reumapotilaista. Reumapotilaiden kudosnäytteiden uudelleentutkiminen lisäsi amyloidoosin määrän kaksinkertaiseksi ruumiinavauksessa todettuihin verrattuna. Näillä potilailla tulehdusarvot olivat olleet korkeammat ja reuma oli kestänyt pidempään. Heistä vain puolella oli elinaikana todettu munuaisten vajaatoiminta tai valkuaisvirtsaisuus. Reumapotilaiden tavallisimpia kuolinsyitä olivat sydän- ja verisuonitaudit, reuma ja infektiot. Reumapotilaiden sepelvaltimotauti näyttää olevan alidiagnosoitu. Sepelvaltimotaudin aktiivinen etsiminen ja tehokas hoito ovat tärkeitä kuolleisuuden vähentämisessä. Amyloidoosi myös voi jäädä toteamatta elinaikana. Amyloidoosia kannattaa etsiä etenkin reumapotilailta, joilla on munuaisten vajaatoiminta, valkuaisvirtsaisuus tai pitkään kestänyt ja aktiivi reuma. Amyloidoosin varhainen toteaminen on tärkeää, jotta voidaan estää sen eteneminen reuman hoitoa tehostamalla.
Show more