The initial treatment strategy and the long-term outcome of early rheumatoid arthritis with special interest in the FIN-RACo trial and the current Finnish practice

Nivelreuman luonnollinen kulku johtaa tulehduksen kautta nivelten tuhoutumiseen, toiminta- ja työkyvyn alenemiseen ja lisääntyneeseen kuolleisuuteen. Viime vuosikymmeninä reumalääkkeiden on todettu estävän, tai ainakin hidastavan tätä taudinkulkua, ja niinpä nykyään maailmanlaajuisesti nivelreumaan suositellaan varhaista ja aggressiivista hoitoa, joskin hoitosuositukset eri maissa eroavat jonkin verran toisistaan. Suomessa, suurelta osin kansallisen monikeskustutkimuksen, FIN-REKO:n (Finnish Rheumatoid Arthritis Combination Therapy Trial, FIN-RACo) suotuisten 2- ja 5-vuotistulosten ansiosta, aktiivisen nivelreuman aloitushoidoksi suositellaan kolmen reumalääkkeen ja pieniannoksisen kortisonin yhdistelmähoitoa. Nykyisessä tutkimuksessa halusimme tutkia tämän hoidon pitkäaikaisvaikutuksia ja turvallisuutta analysoimalla FIN-REKO-tutkimuksen 11 vuoden seurantatulokset. Lisäksi pyrimme kartoittamaan kuinka reumalääkkeitä Suomessa käytetään varhaisessa nivelreumassa, ja onko mahdollisesti aikaisempaa aktiivisemmilla hoitokäytännöillä voitu vähentää pysyvää työkyvyttömyyttä. Vuonna 1993 alkaneessa FIN-REKO-tutkimuksessa 199 varhaista nivelreumaa sairastavaa potilasta satunnaistettiin saamaan joko kolmen reumalääkkeen ja kortisonin yhdistelmähoitoa (FIN-RACo-ryhmä) tai yksittäistä reumalääkettä ja tarvittaessa kortisonia (SINGLE-ryhmä). Hoito molemmissa ryhmissä tähtäsi täyteen oireettomuuteen eli remissioon. Kahden vuoden jälkeen hoidot olivat vapaat. Yhteentoista vuoteen asti 138 potilasta jatkoi seurannassa. Toimintakyky oli molemmissa ryhmissä säilynyt hyvänä, puolella potilaista ei ollut siinä minkäänlaista rajoitusta. Remissiot olivat kuitenkin yleisempiä FIN-RACo-ryhmässä (37%) kuin SINGLE-ryhmässä (19%). Lisäksi pysyviä vaurioita osoittavia, röntgenkuvissa näkyviä muutoksia oli vähemmän FIN-RACo-ryhmässä kuin SINGLE-ryhmässä, joskin molempien ryhmien röntgenlöydökset olivat vähäisempiä kuin useissa aikaisemmissa tutkimuksissa on todettu. Remissioon tähtäävä hoito hillitsee siis pitkälläkin tähtäimellä nivelreuman etenemistä paremmin kuin vanhanaikainen, konservatiivisempi hoito. Yhdistelmälääkityksellä toteutettuna se on kuitenkin vielä tehokkaampaa kuin yhdellä reumalääkkeellä. Tutkimuksen toisessa osassa kerättiin Kansaneläkelaitoksen (Kela) rekisteritiedoista kaikki Suomessa vuosina 2000-2007 nivelreumaan sairastuneet 14 878 potilasta, joiden tiedot analysoitiin kaksivuotiskohorteittain (2000-01, 2002-03, 2004-05, 2006-07). Erityisesti mielenkiinto kohdistui potilaiden ensimmäisen vuoden aikana ostamiin reumalääkkeisiin sekä toisaalta työkyvyttömyyden ilmaantuvuuteen vuoden 2008 loppuun mennessä. Tässä tutkimuksen osassa todettiin, että useista muista maista raportoituun tilanteeseen verrattuna Suomessa on hoidettu tuoretta nivelreumaa aktiivisesti jo tutkimusjakson alussa, mutta hoito on käynyt jatkuvasti aktiivisemmaksi niin, että tutkimusjakson lopulla yli puolelle potilaista aloitettiin ensimmäisen kolmen kuukauden aikana usean reumalääkkeen yhdistelmähoito, metotreksaattia sai lähes 70%, ja ilman mitään reumalääkettä oli vain alle 5% potilaista. Diagnoosihetkellä työkykyisistä potilaista oli kahden vuoden seurannan aikana nivelreuman vuoksi työkyvyttömyyseläkkeelle jäänyt ensimmäisestä vuosikohortista (2000-01) 8.9%, mutta viimeisestä (2006-07) vain 4.8%. Työkyvyttömyyden vähenemistä selittäviä tekijöitä ei tästä tutkimusaineistossa valitettavasti voitu analysoida. Väitöskirjan päälöydökset olivat siis, että aktiivinen, remissioon pyrkivä hoitostrategia tuottaa hyvän kliinisen ja radiologisen tuloksen useimmilla potilailla. Kuitenkin alkuvaiheessa kolmen lääkkeen yhdistelmähoitoa saaneilla potilailla on vielä pitkäaikaisseurannassakin enemmän remissioita ja vähemmän radiologista etenemistä kuin alkuvaiheessa yksittäishoitoa saaneilla. Tällä vuosituhannella varhaisen nivelreuman hoito on Suomessa muuttunut entistäkin aktiivisemmaksi. Samaan aikaan varhaisesta nivelreumasta johtuvan pitkäaikaisen työkyvyttömyyden ilmaantuvuus on alentunut.Background. The natural course of rheumatoid arthritis (RA) leads through joint inflammation to progressive joint damage and lost functional ability, elevated incidence of work disability and even increased mortality. Effective treatment with disease modifying antirheumatic drugs (DMARDs) has been shown to prevent or delay this progression. Thus, an early and aggressive treatment of RA is recommended internationally. In Finland, mainly due to beneficial 2- and 5-year results of a national multicenter study, the Finnish Rheumatoid Arthritis Combination Therapy Trial (FIN-RACo), a combination of 3 DMARDs and a small dose glucocorticoid (GC) is recommended as the initial treatment in active RA. In this study we aimed to elucidate the long-term effects and safety of such aggressive initial treatment by analysing the 11-year follow-up results of the FIN-RACo Trial. We also wanted to clarify how DMARDs are currently used in early RA in Finland and whether the possible change in treatments may have affected the incidence of work disability (WD) in early RA. Methods. In the FIN-RACo study 199 patients with early active RA were randomized to treatment with a combination of methotrexate (MTX), sulfasalazine (SASP), and hydroxychloroquine (HCQ) with prednisolone (FIN-RACo group) or treatment with a single DMARD (initially, SASP) with or without prednisolone (SINGLE group). The treatment in both groups aimed at remission. After 2 years, the treatment strategy became unrestricted. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and remission with the American College of Rheumatology (ACR) criteria (I). The radiographs of hands and feet, as well as of large joints were assessed and scored according to the Larsen method (II). In the second part of the study, data for all new Finnish RA patients was collected from a nationwide register maintained by the Social Insurance Institution (SII) from 1.1.2000 to 31.12.2007. Patient cohorts were analyzed in 2-year time periods (2000-01, 2002-03, 2004-05, 2006-07) and DMARDs purchased by them during the first year after the diagnosis were registered (III). For the patients available to labour force at the time of the diagnosis the incidence of continuous WD up to 31 Dec 2008 was clarified (IV). Results. At 11 years, 138 patients were assessed (68 in the FIN-RACo group and 70 in the SINGLE group). The mean ± SD HAQ scores were 0.34 ± 0.54 in the FIN-RACo group and 0.38 ± 0.58 in the SINGLE group (p = 0.88). ACR remission was achieved by 37% (95% CI: 26 to 49) of the FIN-RACo group and by 19% (95% CI: 11 to 29) (p = 0.017) of the SINGLE group (I). The radiographs of hands and feet were available in 65 patients in each group at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95 % CI: 12 to 26) in the FIN-RACo group and 27 (95 % CI: 22 to 33) in the SINGLE group (p = 0.037). Respectively 87% (95% CI: 74 to 94) and 72% (95% CI: 58 to 84) of the patients in the FIN-RACo and the SINGLE groups had no erosive changes in large joints at 11 years (II). From the SII database 14 878 (68.0% female, 62.6% RF-positive) patients with a new diagnosis of RA between 2000-07 were identified. In the first cohort single DMARD treatment (56.1%) was the most commonly used strategy during the first 3 months and SASP (63.0%) the most commonly used DMARD during the first year. In the last cohorts the respective treatments were combination DMARDs (55.3%) and methotrexate (69.0%). The change in treatment strategies and in DMARDs used was highly significant (p Conclusions. Targeting remission with tight clinical controls results in good functional, clinical and radiographic outcomes in most RA patients. However, compared to initial single-DMARD therapy, initial combination DMARDs results in higher rates of patients achieving strict ACR remission and in lower radiographic progression even in the long term. During this millennium in Finland, increasingly active treatments have been adopted in the treatment of early RA and the incidence of continuous work disability has declined

The initial treatment strategy and the long-term outcome of early rheumatoid arthritis with special interest in the FIN-RACo trial and the current Finnish practice

Nivelreuman luonnollinen kulku johtaa tulehduksen kautta nivelten tuhoutumiseen, toiminta- ja työkyvyn alenemiseen ja lisääntyneeseen kuolleisuuteen. Viime vuosikymmeninä reumalääkkeiden on todettu estävän, tai ainakin hidastavan tätä taudinkulkua, ja niinpä nykyään maailmanlaajuisesti nivelreumaan suositellaan varhaista ja aggressiivista hoitoa, joskin hoitosuositukset eri maissa eroavat jonkin verran toisistaan. Suomessa, suurelta osin kansallisen monikeskustutkimuksen, FIN-REKO:n (Finnish Rheumatoid Arthritis Combination Therapy Trial, FIN-RACo) suotuisten 2- ja 5-vuotistulosten ansiosta, aktiivisen nivelreuman aloitushoidoksi suositellaan kolmen reumalääkkeen ja pieniannoksisen kortisonin yhdistelmähoitoa. Nykyisessä tutkimuksessa halusimme tutkia tämän hoidon pitkäaikaisvaikutuksia ja turvallisuutta analysoimalla FIN-REKO-tutkimuksen 11 vuoden seurantatulokset. Lisäksi pyrimme kartoittamaan kuinka reumalääkkeitä Suomessa käytetään varhaisessa nivelreumassa, ja onko mahdollisesti aikaisempaa aktiivisemmilla hoitokäytännöillä voitu vähentää pysyvää työkyvyttömyyttä. Vuonna 1993 alkaneessa FIN-REKO-tutkimuksessa 199 varhaista nivelreumaa sairastavaa potilasta satunnaistettiin saamaan joko kolmen reumalääkkeen ja kortisonin yhdistelmähoitoa (FIN-RACo-ryhmä) tai yksittäistä reumalääkettä ja tarvittaessa kortisonia (SINGLE-ryhmä). Hoito molemmissa ryhmissä tähtäsi täyteen oireettomuuteen eli remissioon. Kahden vuoden jälkeen hoidot olivat vapaat. Yhteentoista vuoteen asti 138 potilasta jatkoi seurannassa. Toimintakyky oli molemmissa ryhmissä säilynyt hyvänä, puolella potilaista ei ollut siinä minkäänlaista rajoitusta. Remissiot olivat kuitenkin yleisempiä FIN-RACo-ryhmässä (37%) kuin SINGLE-ryhmässä (19%). Lisäksi pysyviä vaurioita osoittavia, röntgenkuvissa näkyviä muutoksia oli vähemmän FIN-RACo-ryhmässä kuin SINGLE-ryhmässä, joskin molempien ryhmien röntgenlöydökset olivat vähäisempiä kuin useissa aikaisemmissa tutkimuksissa on todettu. Remissioon tähtäävä hoito hillitsee siis pitkälläkin tähtäimellä nivelreuman etenemistä paremmin kuin vanhanaikainen, konservatiivisempi hoito. Yhdistelmälääkityksellä toteutettuna se on kuitenkin vielä tehokkaampaa kuin yhdellä reumalääkkeellä. Tutkimuksen toisessa osassa kerättiin Kansaneläkelaitoksen (Kela) rekisteritiedoista kaikki Suomessa vuosina 2000-2007 nivelreumaan sairastuneet 14 878 potilasta, joiden tiedot analysoitiin kaksivuotiskohorteittain (2000-01, 2002-03, 2004-05, 2006-07). Erityisesti mielenkiinto kohdistui potilaiden ensimmäisen vuoden aikana ostamiin reumalääkkeisiin sekä toisaalta työkyvyttömyyden ilmaantuvuuteen vuoden 2008 loppuun mennessä. Tässä tutkimuksen osassa todettiin, että useista muista maista raportoituun tilanteeseen verrattuna Suomessa on hoidettu tuoretta nivelreumaa aktiivisesti jo tutkimusjakson alussa, mutta hoito on käynyt jatkuvasti aktiivisemmaksi niin, että tutkimusjakson lopulla yli puolelle potilaista aloitettiin ensimmäisen kolmen kuukauden aikana usean reumalääkkeen yhdistelmähoito, metotreksaattia sai lähes 70%, ja ilman mitään reumalääkettä oli vain alle 5% potilaista. Diagnoosihetkellä työkykyisistä potilaista oli kahden vuoden seurannan aikana nivelreuman vuoksi työkyvyttömyyseläkkeelle jäänyt ensimmäisestä vuosikohortista (2000-01) 8.9%, mutta viimeisestä (2006-07) vain 4.8%. Työkyvyttömyyden vähenemistä selittäviä tekijöitä ei tästä tutkimusaineistossa valitettavasti voitu analysoida. Väitöskirjan päälöydökset olivat siis, että aktiivinen, remissioon pyrkivä hoitostrategia tuottaa hyvän kliinisen ja radiologisen tuloksen useimmilla potilailla. Kuitenkin alkuvaiheessa kolmen lääkkeen yhdistelmähoitoa saaneilla potilailla on vielä pitkäaikaisseurannassakin enemmän remissioita ja vähemmän radiologista etenemistä kuin alkuvaiheessa yksittäishoitoa saaneilla. Tällä vuosituhannella varhaisen nivelreuman hoito on Suomessa muuttunut entistäkin aktiivisemmaksi. Samaan aikaan varhaisesta nivelreumasta johtuvan pitkäaikaisen työkyvyttömyyden ilmaantuvuus on alentunut.Background. The natural course of rheumatoid arthritis (RA) leads through joint inflammation to progressive joint damage and lost functional ability, elevated incidence of work disability and even increased mortality. Effective treatment with disease modifying antirheumatic drugs (DMARDs) has been shown to prevent or delay this progression. Thus, an early and aggressive treatment of RA is recommended internationally. In Finland, mainly due to beneficial 2- and 5-year results of a national multicenter study, the Finnish Rheumatoid Arthritis Combination Therapy Trial (FIN-RACo), a combination of 3 DMARDs and a small dose glucocorticoid (GC) is recommended as the initial treatment in active RA. In this study we aimed to elucidate the long-term effects and safety of such aggressive initial treatment by analysing the 11-year follow-up results of the FIN-RACo Trial. We also wanted to clarify how DMARDs are currently used in early RA in Finland and whether the possible change in treatments may have affected the incidence of work disability (WD) in early RA. Methods. In the FIN-RACo study 199 patients with early active RA were randomized to treatment with a combination of methotrexate (MTX), sulfasalazine (SASP), and hydroxychloroquine (HCQ) with prednisolone (FIN-RACo group) or treatment with a single DMARD (initially, SASP) with or without prednisolone (SINGLE group). The treatment in both groups aimed at remission. After 2 years, the treatment strategy became unrestricted. At 11 years, function was assessed with the Health Assessment Questionnaire (HAQ), and remission with the American College of Rheumatology (ACR) criteria (I). The radiographs of hands and feet, as well as of large joints were assessed and scored according to the Larsen method (II). In the second part of the study, data for all new Finnish RA patients was collected from a nationwide register maintained by the Social Insurance Institution (SII) from 1.1.2000 to 31.12.2007. Patient cohorts were analyzed in 2-year time periods (2000-01, 2002-03, 2004-05, 2006-07) and DMARDs purchased by them during the first year after the diagnosis were registered (III). For the patients available to labour force at the time of the diagnosis the incidence of continuous WD up to 31 Dec 2008 was clarified (IV). Results. At 11 years, 138 patients were assessed (68 in the FIN-RACo group and 70 in the SINGLE group). The mean ± SD HAQ scores were 0.34 ± 0.54 in the FIN-RACo group and 0.38 ± 0.58 in the SINGLE group (p = 0.88). ACR remission was achieved by 37% (95% CI: 26 to 49) of the FIN-RACo group and by 19% (95% CI: 11 to 29) (p = 0.017) of the SINGLE group (I). The radiographs of hands and feet were available in 65 patients in each group at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95 % CI: 12 to 26) in the FIN-RACo group and 27 (95 % CI: 22 to 33) in the SINGLE group (p = 0.037). Respectively 87% (95% CI: 74 to 94) and 72% (95% CI: 58 to 84) of the patients in the FIN-RACo and the SINGLE groups had no erosive changes in large joints at 11 years (II). From the SII database 14 878 (68.0% female, 62.6% RF-positive) patients with a new diagnosis of RA between 2000-07 were identified. In the first cohort single DMARD treatment (56.1%) was the most commonly used strategy during the first 3 months and SASP (63.0%) the most commonly used DMARD during the first year. In the last cohorts the respective treatments were combination DMARDs (55.3%) and methotrexate (69.0%). The change in treatment strategies and in DMARDs used was highly significant (p Conclusions. Targeting remission with tight clinical controls results in good functional, clinical and radiographic outcomes in most RA patients. However, compared to initial single-DMARD therapy, initial combination DMARDs results in higher rates of patients achieving strict ACR remission and in lower radiographic progression even in the long term. During this millennium in Finland, increasingly active treatments have been adopted in the treatment of early RA and the incidence of continuous work disability has declined

Nivelreuma

Teema : autoimmuunitaudit. English summaryPeer reviewe

Nivelreuma

Teema : autoimmuunitaudit. English summaryPeer reviewe

Impact of early systemic lupus erythematosus on work disability-results from the Finnish nationwide register 2000-2007

Objectives of this study were to examine work disability (WD) and its leading causes in incident SLE patients. Data were derived from the Finnish nationwide registries to identify all non-retired, 18 to 64-year-old incident SLE patients between 2000 and 2007. Sick benefits and WD pensions and the causes for them were monitored until the end of 2008. A total of 446 working-aged, incident SLE patients available for work force (mean age 42 +/- 13 years, 89% females) were found. During the follow-up (median 5.3 years), WD pension was granted to 27 patients. The most common cause was SLE itself (14 patients, 52%), with cumulative incidence of 3.4% (95% CI 1.9 to 5.8) in 5 years and 5.0% (95% CI 3.0 to 8.5) in 8 years, followed by musculoskeletal and psychiatric causes. The age- and sex- adjusted incidence ratio for WD pension in SLE patients due to any cause was 5.4 (95% CI 3.7 to 7.9) compared to the Finnish population. The mean number of WD days was 32 (95% CI 28 to 35) per patient-year among all SLE patients during the follow-up. The study concludes that SLE patients have an increased risk for WD already in early course of the disease.Peer reviewe

Malignancies among newly diagnosed systemic lupus erythematosus patients and their survival

The objective of this study was to evaluate the incidence of malignancies among newly diagnosed systemic lupus erythematosus (SLE) patients compared to reference individuals. Another aim was to assess the survival of SLE patients with malignancy compared to references with malignancy. Finnish adult (>17 years) newly diagnosed SLE patients were identified by their drug reimbursement decisions made during 1.1.2000–31.12.2014 from the register of the Social Insurance Institution. For each case, three population controls were individually selected by age, sex and place of residence. Overall, 1006 SLE patients (women 84%), with a mean age of 45.5 years (SD 16 years) and 3005 population controls were linked to Finnish Cancer Registry, and the information about incident malignancies was retrieved from the day the special reimbursement decision for SLE medication was accepted (index day, ID) until 31.12.2018 or until death. The patients diagnosed with malignancy were followed up until 31.12.2019 considering survival. During the follow-up, 85 SLE patients (women 78%) and 192 controls (women 78%) had developed one or more malignancy after the ID. The incidence rate ratio for any malignancy was 1.41 (95% CI 1.08–1.85). The most common malignancy in SLE patients was non-Hodgkin lymphoma, with twelve cases. SLE patients with malignancy had a lower adjusted 15-year survival than controls with malignancy, 27.1% versus 52.4%, and the adjusted hazard ratio for death was 1.68 (95% CI 1.17–2.43). Our results confirm that SLE patients have a higher risk for overall malignancy. The results also suggest that SLE patients with malignancy have lower survival than their references with malignancy.publishedVersionPeer reviewe

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.Peer reviewe

Pregnancies in patients with systemic lupus erythematosus during 2000–2018 in Finland : a case–control study

Objectives: The aim was to investigate, how pregnancies proceed in patients with systemic lupus erythematosus (SLE) compared to their individually matched population controls. Material and methods: Adult incident SLE patients were identified from the register of new special reimbursement decisions for SLE drugs in 2000–2014. For each patient, 1–3 randomly selected controls from the Population Register Centre were matched. Data regarding pregnancies were obtained from the Finnish Medical Birth Register, Care Register and Register of Congenital Malformations until 2018. The study utilized data from the Drug Purchase Register and educational information from Statistic Finland. Results: A total of 163 deliveries for 103 mothers with SLE and 580 deliveries for 371 population controls were identified. The duration of pregnancies in SLE women was significantly shorter compared to controls (38.9 versus 39.6 weeks). There were more urgent Caesarean Sections. (15% versus 9%) and need for care at neonatal intensive care unit (NICU) (21% versus 11%) among deliveries in SLE mothers. No statistical difference was observed between SLE and control groups in the occurrence of preeclampsia or major congenital malformations. Gestational age was 2.5 weeks shorter when the mother experienced pre-eclampsia. Hydroxychloroquine was purchased by 30% of SLE mothers during pregnancy. Conclusion: The course of pregnancies in Finnish SLE patients seems to be quite moderate compared to controls, and no new safety issues were detected. The low utilization of hydroxychloroquine indicates that the benefits of the drug to pregnancy and disease course are not optimally recognized by specialists treating SLE mothers.Peer reviewe

High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis

Adverse events (AEs) are common during disease-modifying antirheumatic drug (DMARD) treatment, but their influence on treatment results is unclear. We studied AEs in relation to disease activity in early rheumatoid arthritis (RA). Ninety-nine patients started intensive treatment with three conventional synthetic DMARDs (csDMARDs) and oral prednisolone, and were randomized to a 6-month induction treatment with infliximab or placebo. All AEs during the first 12 months of treatment were recorded. We scored each AE based on severity (scale 1-4) and defined the burden of AEs as the sum of these scores. Patients were divided into tertiles according to the burden of AEs. As outcomes, we assessed 28-joint disease activity score (DAS28) levels and remission rates at 12 and 24 months. Three hundred thirty-one AEs in 99 patients were reported, and 27 (8%) were categorized as severe or serious. Mean burden of AEs per patient was 5.4 ± 4.3. Seventy-nine AEs (24%) led to temporary (n = 52) or permanent (n = 27) csDMARD discontinuation. Of discontinuations, 1, 21, and 57 were detected in the first, second, and third tertiles, respectively. DAS28 remission rates decreased across tertiles at 12 months (94, 94, and 76%; p for linearity 0.029) and at 24 months (90, 86, and 70%; p for linearity 0.021). Mean DAS28 levels increased across tertiles at 12 months (1.5 ± 1.0, 1.7 ± 0.9, and 1.9 ± 1.2; p for linearity 0.021) and at 24 months (1.4 ± 0.8, 1.6 ± 1.0, and 1.9 ± 1.1; p for linearity 0.007). High burden of AEs is associated with higher disease activity and lower likelihood of remission in early RA.</div