Article

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.

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    • "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). "
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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.
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