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.

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.

Opioid use frequency in early axial spondyloarthritis in Finland - a pharmacoepidemic register study.

OBJECTIVES: To evaluate opioid use among incident axial spondyloarthritis (axSpA) patients compared to general population. METHODS: From the national register, we identified all adult patients with axSpA (ICD-10 codes M45-46), who between 2010 and 2014 (index date, ID) were for the first time granted special reimbursement for any disease-modifying antirheumatic drugs (DMARDs). Three matched population controls were identified for each patient. Drug purchases were evaluated between 2009-2015, and opioid use was analyzed for one year before and after the ID. The Defined Daily Dose (DDD) was used as a tool to assess the opioid consumption before and after the biological (b) DMARD initiation. RESULTS: We identified 3577 axSpA patients and 10,573 controls. Of these patients, 97.2% started a conventional synthetic (cs) DMARD during a year after ID and 23.4% switched later to a self-injected bDMARD between the ID and 31 Dec 2015 (median follow-up 3.4 years). Opioids were purchased at least once by 29.8% and 21.7% of the patients in the years before and after the ID, respectively, compared to 8.1% and 7.8% of the controls. The proportion of opioid-using patients was greatest during the last quarter before the ID [relative risk (RR) 4.72 (95% CI 4.14 to 5.39)] compared to controls, and it remained higher [RR 2.84 (2.59 to 3.11)] also after the start of csDMARDs. DDD of opioid consumption decreased from 7.7 to 1.6/1000 inhabitants after bDMARD initiation. CONCLUSION: Considerably more axSpA patients than population controls used opioids. The opioid consumption by dose decreased clearly after bDMARD initiation.

Multimorbidity among incident Finnish systemic lupus erythematosus patients during 2000-2017.

The objective of the study was to examine the risk of other morbidities among patients with systemic lupus erythematosus (SLE). A total of 1006 adult new-onset SLE patients were identified during 1.1.2000- 31.12.2014 from the register of Social Insurance Institution. For each case three general population controls matched according to age, sex and place of residence at the index day were sampled from the population register. Both groups were followed up from the index date until the end of 2017 or until death. The national register on specialized care was explored to gather broadly their 12 organ-specific morbidities, which were found among 91.2% of SLE patients and 66.7% of comparators. The rate ratio (RR) was elevated in almost all disease groups. Musculoskeletal, cardiovascular and genitourinary conditions were the most common comorbidities with RRs of 1.82 (1.68 to 1.97), 1.91 (1.76 to 2.08) and 1.91 (1.73 to 2.09), respectively. Men with SLE had a significantly higher risk for diseases of the genitourinary system and endocrine, nutritional and metabolic diseases compared to women with SLE. The risk of concurrent morbidities is essential to note in the care of SLE patients.

First-year drug therapy of new-onset rheumatoid and undifferentiated arthritis: a nationwide register-based study.

BACKGROUND: In this retrospective cohort study, we evaluated the drug therapies used for early rheumatoid (RA) and undifferentiated (UA) arthritis patients. METHODS: From a nationwide register maintained by the Social Insurance Institution, information on sex, date of birth, and date of special medicine reimbursement decision for all new Finnish RA and UA patients between 2011 and 14 were collected, and their DMARD (Disease Modifying Antirheumatic Drug) purchases during the first year after the diagnosis were analyzed. RESULTS: A total of 7338 patients with early RA (67.3% female, 68.1% seropositive) and 2433 with early UA (67.8% female) were identified. DMARDs were initiated during the first month after the diagnosis to 92.0% of the patients with seropositive RA, 90.3% with seronegative RA and to 87.7% with UA (p < 0.001). Respectively, 72.1, 63.4, and 42.9% of the patients (p < 0.001) purchased methotrexate; 49.8, 35.9, and 16.0% (p < 0.001) as part of a DMARD combination during the first month. By the end of the first year after the diagnosis, self-injected biologics were purchased by 2.6, 5.3 and 3.1% (p < 0.001) of them. Only 1.4, 2.6 and 3.0% (p < 0.001) of the patients were not receiving any DMARDs. During the first year, 83.4% of the seropositive RA patients had purchased methotrexate, 50.4% sulfasalazine, 72.1% hydroxychloroquine, and 72.6% prednisolone. CONCLUSIONS: Currently, combination therapy including methotrexate is a common treatment strategy for early seropositive RA in Finland. Despite an easy access to biologics, these drugs are seldom needed during the first year after diagnosis.

Trends towards more active introduction of drug therapy, emphasizing methotrexate and biologic agents, for juvenile idiopathic arthritis.

To evaluate the drug treatment trends in patients with incident juvenile idiopathic arthritis (JIA) in 2006-2014. In Finland, patients are entitled to a special reimbursement for medication if their condition meets certain criteria. We gathered all reimbursement decisions with the ICD-10 diagnosis of M08 for patients under 16 years of age from a nationwide register maintained by Kela, the Social Institution of Finland. A total of 2439 incident cases of JIA were identified. We surveyed their reimbursable drugs purchased for the first time for JIA upon a doctor's prescription in 3-year cohorts (2006-2008, 2009-2011, 2012-2014). Changes of drug treatment for JIA became more active during our study years. Between 2006-2008 and 2011-2014, the introduction of methotrexate (MTX) for the first time within the first 3 months increased from 73% (2006-2008) to 90% (2011-2014) of the patients, IRR (incidence rate ratio) was 1.23 (95% CI 1.10-1.37). The use of parenteral MTX increased even more; IRR was 1.97 (95% CI 1.61-2.41). During the first 2 years of their disease, 18% of the first cohort received subcutaneous biologic agents, while the corresponding proportion in the last cohort was 31%. Biologic agents were more likely to be introduced for patients with early (3 months) MTX administration than for patients without early MTX introduction; HR (hazard ratio) 2.19 (95% CI 1.63-2.93). During the follow-up, MTX administration became more prevalent for the treatment of JIA soon after diagnosis, mostly because of the increase in the use of parenteral MTX.Key Points • The drug therapy for treating juvenile idiopathic arthritis has changed during recent years. • Methotrexate, some other conventional DMARDs, and biologic DMARDs are introduced earlier.

Opioid Use among Patients with Early Inflammatory Arthritides Compared to the General Population.

OBJECTIVE: To assess to what extent the worldwide opioid epidemic affects Finnish patients with early inflammatory arthritis (IA). METHODS: From the nationwide register maintained by the Social Insurance Institution of Finland, we collected all incident adult patients with newly onset seropositive and seronegative rheumatoid arthritis (RA+ and RA-) and undifferentiated arthritis (UA) between 2010 and 2014. For each case, 3 general population (GP) controls were matched according to age, sex, and place of residence. Drug purchases between 2009 and 2015 were evaluated 1 year before and after the index date (date of IA diagnosis), further dividing this time into 3-month periods. RESULTS: A total of 12,115 patients (66% women) were identified. At least 1 opioid purchase was done by 23-27% of the patients 1 year before and 15-20% one year after the index date. Relative risk (RR) of opioid purchases compared to GP was highest during the last 3-month time period before the index date [RR 2.81 (95% CI 2.55-3.09), 3.06 (2.68-3.49), and 4.04 (3.51-4.65) for RA+, RA-, and UA, respectively] but decreased after the index date [RR 1.38 (1.23-1.58), 1.91 (1.63-2.24), and 2.51 (2.15-2.93)]. Up to 4% of the patients were longterm users both before and after the diagnosis. CONCLUSION: During 2009-15 in Finland, opioid use peaked just before the diagnosis of IA but decreased rapidly after that, suggesting effective disease control, especially in seropositive RA. Further, opioids were used to treat arthritis pain of patients with incident RA and UA less often than previously reported from other countries.

Correction to: Trends towards more active introduction of drug therapy, emphasizing methotrexate and biologic agents, for juvenile idiopathic arthritis.

The first and family names of the authors were interchanged and are now presented correctly. The original article has been corrected.

Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with Treat-to-target Strategy: 10-year Results of the NEO-RACo Study.

OBJECTIVE: To evaluate the development of radiological changes of the cervical spine in patients with rheumatoid arthritis (RA) in the NEO-RACo trial treated with an intensive, remission-targeted combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and additional infliximab (IFX) or placebo (PLA) for the first 6 months. METHODS: Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARD and prednisolone, and randomized to double-blindly receive either IFX (FIN-RACo+IFX) or PLA (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict NEO-RACo remission. At the 10-year visit, radiographs of the cervical spine were taken of 85 patients (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group). The study was registered at ClinicalTrials.gov (NCT00908089). RESULTS: There were 4/85 patients (4.7%) with cervical spine involvement (CSI) by 10 years. Atlantoaxial subluxation was found in 2/85 patients (2.4%), both in the FIN-RACo+IFX group, and none in the FIN-RACo+PLA group. Atlantoaxial impaction was found in 1/85 patients (1.2%) in the FIN-RACo+IFX group. Subaxial subluxation was found in 1/85 patients (1.2%). CONCLUSION: Early and intensive remission-targeted treatment has reduced the incidence of CSI and our results show that intensive treatment also prevents its development in the long run.

Early Targeted Combination Treatment With Conventional Synthetic Disease-Modifying Antirheumatic Drugs and Long-Term Outcomes in Rheumatoid Arthritis: Ten-Year Follow-Up Results of a Randomized Clinical Trial.

OBJECTIVE: The short-term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well-established, but the long-term success of such strategies is speculative, as is the role of early add-on biologics. We assessed the 10-year outcomes of patients with early RA treated with initial remission-targeted triple combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 7.5-mg prednisolone, and additional infliximab (IFX) or placebo infusions. METHODS: Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARDs and prednisolone and randomized to double-blind receipt of infusions of either IFX (the Finnish Rheumatoid Arthritis Combination Therapy Trial [FIN-RACo] + IFX) or placebo (FIN-RACo + placebo) during the first 6 months. After 2 years, the treatment strategies became unrestricted, but the treatment goal was strict remission in the TNF-Blocking Therapy in Combination With Disease-Modifying Antirheumatic Drugs in Early Rheumatoid Arthritis (NEO-RACo) study. At 10 years, the clinical and radiographic outcomes and the drug treatments used between 5 and 10 years were assessed. RESULTS: Ninety patients (91%) were followed after 2 years, 43 in the FIN-RACo + IFX and 47 in the FIN-RACo + placebo group. At 10 years, the respective proportions of patients in strict NEO-RACo remission and in Disease Activity Score using 28 joints remission in the FIN-RACo + IFX and FIN-RACo + placebo groups were 46% and 38% (P = 0.46) and 82% and 72% (P = 0.29), respectively. The mean total Sharp/van der Heijde score was 9.8 in the FIN-RACo + IFX and 7.3 in the FIN-RACo + placebo group (P = 0.34). During the 10-year follow-up, 26% of the FIN-RACo + IFX group and 30% of the FIN-RACo + placebo group had received biologics (P = 0.74). CONCLUSION: In early RA, excellent results can be maintained up until 10 years in most patients treated with initial combination csDMARDs and remission-targeted strategy, regardless of initial IFX/placebo infusions.

Increasing incidence and shifting profile of idiopathic inflammatory rheumatic diseases in adults during this millennium.

To explore the trends in the incidence of idiopathic inflammatory rheumatic diseases (IIRDs) after the turn of the millennium. From a nationwide register maintained by the Social Insurance Institution of Finland, we collected all adult patients with IIRDs granted a new special reimbursement for anti-rheumatic drugs between 2000 and 2014. Temporal trends in the incidences of various IIRDs were estimated in three 5-year intervals. A total of 58,405 adult patients were identified. Between 2000-2004 and 2010-2014, the age-adjusted incidence rate of IIRDs increased from 114 to 116/100000 [incidence rate ratio (IRR) 1.03 (95% CI 1.01 to 1.06)] in women and from 67 to 69/100,000 [IRR 1.10 (95% CI 1.06-1.14)] in men. The incidence of seropositive rheumatoid arthritis (RA) remained stable while that of seronegative RA decreased. For other diagnoses, the incidences either increased (unspecified arthritis, psoriatic arthritis, spondyloarthritis), remained stable (reactive arthritis), or decreased (SLE and the group of diseases with the ICD-10 code M35). The gender difference in spondyloarthritis leveled as the incidence in women increased at a higher rate than in men. Mean age at IIRD diagnosis decreased among women. The total age-adjusted incidence of IIRDs has gradually increased, due to the increase in unspecified arthritis, psoriatic arthritis, and spondyloarthritis. This, in addition to the ascending number of individuals at risk in the population, translates into a growing burden to the health care system.

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.

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.

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.

Longterm Work Productivity Costs Due to Absenteeism and Permanent Work Disability in Patients with Early Rheumatoid Arthritis: A Nationwide Register Study of 7831 Patients.

OBJECTIVE: To estimate the development and potential disproportional distribution of longterm productivity costs (PC) and their determinants leading to work absenteeism and permanent work disability in working-aged patients with early rheumatoid arthritis (RA). METHODS: A cohort of subjects with early RA was created by identifying the new cases of RA from the national drug reimbursement register that had been granted a special reimbursement for their antirheumatic medications for RA from 2000-2007. The dataset was enriched by cross-linking with other national registries detailing work absenteeism days and permanent disability pensions. In the base case, the human capital approach was applied to estimate PC based on subjects' annual number of absenteeism days and incomes. Hurdle regression analysis was applied to study the determinants of PC. RESULTS: Among the 7831 subjects with early RA, the mean (bootstrapped 95% CI) annual PC per person-observation year was €4800 (4547-5070). The annual PC declined after the first year of RA diagnosis, but increased significantly in subsequent years. In addition, the PC was heavily disproportionally concentrated in a small fraction of patients with RA, because only around 20% of patients accounted for the majority of total annual PC. The initiation of active drug treatment during the first 3 months after RA diagnosis significantly reduced the cumulative PC when compared with no drug treatment. CONCLUSION: The longterm PC increased significantly in parallel with years elapsing after RA diagnosis. Further, the majority of these PC are incurred by a small proportion of patients.

Early treatment intensification induces favourable radiographic outcomes according to predicted versus observed radiographic progression in early rheumatoid arthritis: a subanalysis of the randomised FIN-RACo and NEO-RACo trials.

OBJECTIVES: Predicted versus observed radiographic progression in early rheumatoid arthritis (POPeRA) was applied to demonstrate how various treatment modalities affect and potentially minimise radiographic progression over time. METHODS: The POPeRA method utilises the baseline radiographic score and patient-reported symptom duration to predict radiographic outcomes. It was applied at baseline, 2, and 5 years to patients with eRA from the randomised Finnish RA Combination trial (FIN-RACo) (n=144) and New Finnish RA Combination Therapy (NEO-RACo) (n=90) trials. For FIN-RACo, patients were randomised either to a single DMARD (sulfasalazine, with or without prednisolone) or to combination therapy (methotrexate+sulfasalazine+hydroxychloroquine, i.e. triple therapy, with prednisolone). In NEO-RACo, all patients were assigned intensified combination therapy (including 7.5 mg prednisolone/day) plus a randomised 6-month induction of either placebo or anti-TNF treatment (infliximab). RESULTS: In FIN-RACo, combination versus monotherapy resulted in superior outcomes in the change from predicted progression over 2 and 5 years (mean 35.7% reduction vs. -32.9%, a worsening from predicted, p=0.001; 34.2% vs. -17.8%, p=0.003, respectively). In NEO-RACo, combination+anti-TNF induction led to significantly greater reductions from predicted progression than combination+placebo, both at 2 and 5 years of follow-up (98.5% vs. 83.4%, p=0.005; 92.4% vs. 82.5%, p=0.027, respectively). Importantly, anti-TNF add-on led to superior reductions from predicted among RF-positive patients (2 years: 97.4% vs. 80.4%, p=0.009; 5 years: 90.2% vs. 80.1%, p=0.030), but not among RF-negative patients. CONCLUSIONS: These results confirm that conventional combination therapy in eRA has a long-term radiographic benefit versus monotherapy. Through POPeRA, it was made evident that anti-TNF induction therapy for 6 months further increases the long-term radiographic benefit of combination therapy in RF-positive patients.

Intra-articular glucocorticoid injections should not be neglected in the remission targeted treatment of early rheumatoid arthritis: a post hoc analysis from the NEO-RACo trial.

OBJECTIVES: To study the effects of neglecting intra-articular glucocorticoid injections (IAGCIs) into swollen joints in early rheumatoid arthritis (RA). METHODS: Ninety-nine patients with early, DMARD naive RA were treated, aiming at remission, with methotrexate, sulfasalazine, hydroxychloroquine, low-dose oral prednisolone and, when needed, IAGCIs for 2 years, and randomised to receive infliximab or placebo from weeks 4 to 26. During each of the 15 study visits, patients were scored retrospectively 0.2-0.4 points (depending on the number of non-injected joints) if IAGCIs to all swollen joints were not given. Patients were divided into tertiles by their cumulative scores for neglected injections (CSNI) over 24 months. 28-joint disease activity score (DAS28) area under the curve (AUC) between 0-24 months, remission rates, changes in quality of life, and radiological changes during the follow-up were assessed. Trends across tertiles of CSNI were tested with generalised linear models. RESULTS: Higher CSNI was associated with lower strict remission rates (p=0.005), and lower quality of life (p=0.004) at 24 months, and higher DAS28 AUC (p<0.001) during the follow-up. At 24 months, DAS28 remission rates were 90%, 93% and 76% (p=0.081), and strict remission rates were 74%, 77% and 39% by tertiles of CSNI. No significant differences were observed in radiological progression (p=0.089). IAGCIs were well tolerated. CONCLUSIONS: Neglecting IAGCIs into swollen joints is associated with lower remission rates, higher disease activity, and lower quality of life. Hence, IAGCIs should be used as an integral part of the targeted treatment of early RA.

Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy.

OBJECTIVE: Because of the role of tumor necrosis factor (TNF) in host defense, it was hypothesized that its inhibition might lead to an increased risk of malignancies and infections. The objective of our study was to assess the incidence of serious infections leading to hospitalization and malignancies among patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or rituximab (RTX) therapy. METHODS: The study population was identified from the National Register for Biologic Treatment in Finland and the hospital records of Central Finland Central Hospital for conventional disease-modifying antirheumatic drug (cDMARD) users. Data on infections and malignancies were acquired from national healthcare registers. A Poisson model was used to calculate the adjusted incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis, year of the beginning of the followup, rheumatoid factor status, Disease Activity Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior serious infection, prior biologic use, and time-updated use of methotrexate, sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders. RESULTS: In total, during the followup of 10,994 patient-years, 92 malignancies and 341 serious infections were included in the analyses. The aIRR of infections compared to cDMARD users were 1.2 (95% CI 0.63-2.3), 0.84 (95% CI 0.53-1.3), 0.98 (95% CI 0.60-1.6), and 1.1 (95% CI 0.59-1.9) for the patients treated with infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates of malignancies were highest among the users of cDMARD and RTX, and lowest among patients treated with IFX with no differences in aIRR. CONCLUSION: Our results provide some reassurance of the safety of biologic treatments in the treatment of RA.

Failure in longterm treatment is rare in actively treated patients with rheumatoid arthritis, but may be predicted by high health assessment score at baseline and by residual disease activity at 3 and 6 months: the 5-year followup results of the randomized clinical NEO-RACo trial.

OBJECTIVE: With modern initial aggressive combination treatments with synthetic disease-modifying antirheumatic drugs (sDMARD), most patients with rheumatoid arthritis (RA) achieve remission, have marginal radiographic progression, and sustain normal function. Here we aim to identify the patients failing these targets even after aggressive treatment. METHODS: Ninety-nine patients with early, active RA were treated with a combination of 3 sDMARD and prednisolone (PRD), and either infliximab or placebo infusions during the first 6 months, aiming at strict remission. After 24 months, the treatments became unrestricted. At 60 months, 4 evident clinical features of treatment failure were defined: area under curve (AUC) between 6-60 months for disease activity score assessing 28 joints > 2.6; AUC 6-60 for health assessment questionnaire > 0.5; progression in total Sharp/van der Heijde score 0-60 months > 3 units; and need of PRD or biologic DMARD treatment at 60 months. RESULTS: A total of 93 patients were followed up for 60 months. Of them, 45 had no features of treatment failure, 30 had 1, 10 had 2, 7 had 3, and 1 patient had all 4 features. Having 2-4 features of treatment failure at 5 years was predicted by the health assessment score at baseline, and by even low residual disease activity at 3 and 6 months. CONCLUSIONS: Only 20% of the patients with RA treated early with combination sDMARD and PRD have more than 1 clinical feature of treatment failure at 60 months. Residual clinical disease activity at 3-6 months was the most important predictor for identifying these patients. The study was registered at www.clintrials.gov (NCT00908089).