Swedish Arthritis Treatment Group Register Research Articles

Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis: what is the role of inflammation control?

Objective While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. Method Bionaïve PsA patients starting a first anti-TNF therapy 2004–2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. Results Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator’s global assessment were associated with a lower risk of 12-month refractory pain. Conclusions A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.

Sustained Remission Improves Physical Function in Patients with Established Rheumatoid Arthritis, and Should Be a Treatment Goal: A Prospective Observational Cohort Study from Southern Sweden.

It has been proposed that remission should be maintained throughout the course of rheumatoid arthritis (RA); however, the evidence supporting this is limited. Physical function measured by the Health Assessment Questionnaire (HAQ) is a major outcome in RA, and HAQ is shown to be one of the strongest predictors of longterm outcomes. The purpose of this study was to investigate the physical function over a long time in patients with RA who achieved sustained remission (SR) compared with that of patients occasionally achieving remission [non-sustained remission (NSR)]. Patients with RA treated with antitumor necrosis factor and included in the South Swedish Arthritis Treatment Group register were eligible for this study. We identified patients with a Disease Activity Score at 28 joints (DAS28) < 2.6 or Simplified Disease Activity Index (SDAI) ≤ 3.3 at some point and those who achieved SR, i.e., remission during consecutive visits for at least 6 months. The course of functional status was assessed using the HAQ at each visit. Of the 2416 patients, 1177 (48.7%) reached DAS28 remission at some point. SR was achieved by 382 (15.8%) for the DAS28 and 186 (7.7%) for the SDAI criteria. Comparing the SR and NSR groups, HAQ improved during the first 12 months in the DAS28 remission. HAQ continued to improve relatively as long as SR was maintained. A higher proportion of patients in SR reached full physical function. In patients with established RA, physical function measured by the HAQ improves in patients reaching SR compared with patients who only occasionally reach remission. The improvement continues while in remission, which supports that maintaining remission should be a treatment goal.

AB0314 The survival rates of biologics treated patients at the centre de rhumatologie de l’est du quebec : description of the real world, canadian patient cohort.

BackgroundIn recent years, major advance has been made in the treatment of rheumatoid arthritis (RA). The efficacy of tumor necrosis factor-α (TNF-α) inhibitor has been demonstrated in different controlled clinical...

OP0189 Long term work disability in anti-TNF therapy treated patients with psoriatic arthritis: A population-based cohort study

BackgroundReduced work ability leading to sick leave is a common consequence of psoriatic arthritis (PsA). TNF-antagonist therapy has been a major advance in treating several aspects of PsA. Little is...

FRI0159 Severe extra-articular manifestations in rheumatoid arthritis: risk factors and incidence in relation to treatment with tnf-inhibitors

BackgroundExtra-articular rheumatoid arthritis (ExRA) manifestations are associated with increased comorbidity and premature mortality. While tumour necrosis factor (TNF)-inhibitors efficiently reduce arthritis, their impact on the risk of ExRA is still...

Long-term work disability in patients with psoriatic arthritis treated with anti-tumour necrosis factor: a population-based regional Swedish cohort study

ObjectiveTo study long-term work disability before and after tumour necrosis factor (TNF)-antagonist therapy in patients with psoriatic arthritis (PsA).MethodsUsing the population-based South Swedish Arthritis Treatment Group Register, we identified 191...

Sick leave in patients with ankylosing spondylitis before and after anti-TNF therapy: a population-based cohort study

To study levels of sick leave and disability pension before and after TNF-antagonist therapy in AS patients. Using the population-based South Swedish Arthritis Treatment Group register, we identified 139 AS patients (aged 18-58 years, 78% men), who between January 2002 and December 2008 started their first treatment with adalimumab, etanercept or infliximab. We linked data to the payment register by the Swedish Social Insurance Agency and calculated the proportion on sick leave in 30-day intervals from 12 months before treatment start until 12 months after. For each AS patient, we randomly selected four subjects from the general population matched for age, sex and area of residence. One to 3 months before treatment, an average of 24% of AS patients were on sick leave. During the first 6 months after treatment start, this fraction dropped to 15%, and further declined to 12% at 12 months (P < 0.001). Comparing AS patients with the general population, the relative risk of being on sick leave 3 months before treatment, treatment start and 12 months after treatment start was 8.0 (95% CI 4.6, 13.9), 9.2 (95% CI 5.4, 15.7) and 4.0 (95% CI 2.1, 6.3), respectively. The decrease in sick leave was not substantially offset by changes in disability pension. There is a decline in sick leave during the first 12 months after initiation of TNF-antagonist treatment in AS patients not explained by societal factors or secular trends. The proportion of AS patients on disability pension remained unchanged during the observation period.

Decrease in sick leave among patients with rheumatoid arthritis in the first 12 months after start of treatment with tumour necrosis factor antagonists: a population-based controlled cohort study

ObjectiveTo investigate the effect of tumour necrosis factor (TNF) antagonist treatment of patients with rheumatoid arthritis (RA) on sick leave (SL) and disability pension (DP) in a population-based setting in...

Presence of peripheral arthritis and male sex predicting continuation of anti–tumor necrosis factor therapy in ankylosing spondylitis: An observational prospective cohort study from the South Swedish arthritis treatment group register

To examine clinical characteristics as possible predictors of long-term treatment continuation with adalimumab, etanercept, and infliximab in ankylosing spondylitis (AS) patients who had never taken biologics treated in clinical practice. Patients in southern Sweden with active AS starting biologic therapy for the first time between October 1999 and December 2008 (n = 243, 75% men) were included in a structured clinical followup over 2 years. Patients with clinical spondylitis had not responded to at least 2 nonsteroidal antiinflammatory drugs, whereas patients who also had peripheral arthritis (n = 121) had additionally failed at least 1 conventional disease-modifying antirheumatic drug (DMARD) treatment course. The mean ± SD age at inclusion was 43 ± 12 years, with a mean ± SD disease duration prior to treatment of 16 ± 12 years. The 2-year drug continuation rate was 74%. Male sex (hazard ratio [HR] of premature discontinuation 0.36 [95% confidence interval (95% CI) 0.19-0.68]) and the presence of peripheral arthritis (HR 0.49 [95% CI 0.27-0.88]) were found to be significant predictors of better drug survival. Furthermore, a trend was seen for more favorable drug continuation on treatment with etanercept as compared with infliximab (HR 0.50 [95% CI 0.25-1.04], P = 0.062), whereas no differences were found comparing the 3 anti-tumor necrosis factor agents in other ways. Higher baseline C-reactive protein level (HR 0.99 [95% CI 0.97-1.00], P = 0.12) and concomitant treatment with nonbiologic DMARDs (HR 0.61 [95% CI 0.34-1.10], P = 0.10) also showed trends to entail better drug adherence. AS patients in this study have an excellent 2-year drug survival rate of 74%. Significant predictors for treatment continuation in this study were male sex and the presence of peripheral arthritis.

Prevalence and incidence of rheumatoid arthritis in southern Sweden 2008 and their relation to prescribed biologics

To gain updated estimates of prevalence and incidence of RA and proportion on biological treatment in southern Sweden. Inpatient and outpatient health care provided to residents in the southernmost county of Sweden (1.2 million inhabitants) is registered in the Skåne Health Care Register (SHCR). We identified residents aged > or = 20 years who had received a diagnosis of RA at least twice during 2003-08. Valid point prevalence estimates by 31 December 2008 were obtained by linkage to the Swedish population register, and information on biological treatment was obtained from the South Swedish Arthritis Treatment Group register. We also tested our estimates of RA occurrence in a series of sensitivity analyses to investigate the effect of altered case criteria and the uncertainty generated by clinical visits without diagnoses. The prevalence of RA in adults was estimated to 0.66% (women = 0.94%, men = 0.37%). The prevalence peaked at age 70-79 years (women = 2.1%, men = 1.1%) before dropping in those aged > or = 80 years. Of prevalent cases, 20% had ongoing biological treatment, a percentage that was highest in women aged 40-49 years (36%). The incidence of RA in 2008 was estimated as 50/100,000 (women = 68/100,000, men = 32/100,000). When compared with a previous report from southern Sweden, the prevalence of RA seems not to have declined in the last decade. The proportion of patients with ongoing biological treatment was slightly higher in women than men. SHCR data are promising additions to other methods to gain frequency estimates of clinically important disease in a timely and cost-efficient manner.

Differences in Longitudinal Disease and Treatment Characteristics of Patients with Rheumatoid Arthritis Replying and Not Replying to a Postal Questionnaire. Experience from a Biologics Register in Southern Sweden

Studies on patients not answering postal questionnaires are scarce. We assessed the demographics and longitudinal disease and treatment characteristics of patients with rheumatoid arthritis (RA) in a Swedish biologics register who replied and who did not reply to a postal questionnaire. In the South Swedish Arthritis Treatment Group register, we have detailed disease severity characteristics at baseline and at followup for rheumatology patients taking biologic drugs. In 2005 a questionnaire on smoking, comorbidities, education, and ethnicity was sent to 1234 RA patients who had started their first biologic drug. In total, 989 subjects (80%) answered the questionnaire. The 245 (20%) who did not answer generally had more severe RA [higher Disease Activity Score, worse Health Assessment Questionnaire score, higher visual analog scale scores for general health and pain at baseline and at followup, and stopped the drug treatment more frequently (72% vs 53%; p=0.0001)]. There were no statistically significant differences in gender and disease duration between those who replied and those who did not reply, but in general the patients who did not reply were younger. Patients with RA in a Swedish biologics register not replying to a postal questionnaire had more severe RA and stopped biological drug treatment more frequently. Thus a detailed analysis of prospectively collected data can clarify selection bias introduced by subjects who do not answer a postal questionnaire, which may influence the validity and interpretation of results from postal survey studies.

Costs and outcomes for patients with rheumatoid arthritis treated with biological drugs in Sweden: a model based on registry data

Objective: To design an economic model describing the costs and outcomes for patients treated with tumour necrosis factor alpha (TNFα) inhibitors for rheumatoid arthritis (RA) in current clinical practice in Sweden, to be used as a tool to estimate cost-effectiveness of the next generation of treatments.Methods: The model was constructed as a discrete event simulation (DES) model analysed at patient level. It contains treatment and outcome data for 1903 patients followed in the RA registry for biological drugs in southern Sweden between 1999 and 2007 [the Southern Swedish Arthritis Treatment Group (SSATG) Register]. Resource consumption was based on a survey of 1027 patients in the same region. Costs and quality-adjusted life years (QALYs) are presented for 10 (5) years, for patients with the mean characteristics at treatment start in SSATG [Health Assessment Questionnaire (HAQ) score 1.33, disease duration 12.1 years, age 55 years], but also for patients with more or less severe disease. Cost and outcomes (QALYs) are discounted with 3%.Results: The 10-year costs in the base case amount to USD336 000 (SD USD 64 000) or EUR 223 000, with a total of 4.4 QALYs. Over 5 years, the costs amount to USD 208 000 or EUR 138 000 and QALYs to 2.5. The results were most sensitive to HAQ level at treatment start, but also to underlying disease progression, age, and disease duration. Starting treatment at a lower HAQ level (0.85) reduces costs by 10% and increase QALYs by 20%.Conclusion: This analysis is based on the longest available follow-up for patients treated with TNFα inhibitors and provides an opportunity to explore treatment strategies when new therapies become available using actual clinical practice data.

Dose escalation of infliximab therapy in arthritis patients is related to diagnosis and concomitant methotrexate treatment: observational results from the South Swedish Arthritis Treatment Group register

To study frequency of dose escalation in infliximab-treated patients and to identify possible predictors thereof. Patients with chronic arthritis initiating their first course of anti-TNF treatment with infliximab at Lund University Hospital were included in a structured clinical follow-up protocol. Information on diagnosis, drug dosage, disease duration, previous and ongoing DMARDs, treatment start and cessation were prospectively collected during the period March 1999 through February 2007. All patients were started on a dose of 3 mg/kg at time 0, week 2, week 6 and then every eighth week independent of diagnosis and were followed for a period of 2 yrs. A total of 206 patients were included in the study. Thirty-two of the patients had PsA, 25 had AS and 149 patients had RA. A minor dose escalation, defined as less than doubling of the dosage, was observed for 53, 48 and 42% of the patients with PsA, AS and RA, respectively. The corresponding values for major dose escalation was observed for 19, 8 and 15% of the patients, respectively. Regression analysis showed that patients with a diagnosis of PsA (P = 0.03), longer follow-up period (P < 0.01), and lack of concomitant MTX treatment (P = 0.03) were significantly associated with risk of dose escalation. Dose escalations were performed in 59% of all infliximab-treated patients during the first 2 yrs of treatment. Our data suggest that PsA patients might require higher dosages than RA and AS patients.

Optimal Public Goods Provision: Implications of Endogenizing the Labor/Leisure Choice

<h3>Background</h3> “Head to head” studies comparing the efficacy and tolerability of different TNF inhibitors are scarce, in particular the comparison between certolizumab pegol and golimumab. <h3>Objectives</h3> To compare the efficaciousness, drug survival and tolerability of certolizumab-pegol and golimumab in adult patients with establish arthritis (RA, JIA, SpA or unspecified polyarthritis) starting these treatments between February 2010 and December 2013 at out-patient unit at the Skåne University Hospital, Department of Rheumatology Lund/Malmö and two associated private rheumatology units. <h3>Methods</h3> All patients starting treatment with biologics were consecutively included in the South Swedish Arthritis Treatment Group (SSATG) register and regularly followed up according the standard protocol including: SJC/TJC, CRP, ESR, physicians global assessment of disease activity, patients9 assessment of disease activity and pain (VAS global and VAS pain) and HAQ. Last follow up date was October 17th 2016. Kaplan-Meier survival analysis was used to estimate the drug survival. Possible predictors of drug survival were analysed using Cox regression model. <h3>Results</h3> In total, 352 patients (71% women, mean age 51 years, mean disease duration 12 years, started these treatments during study period. Of these, 168 received golimumab and 184 certulizumab-pegol. Mean treatment time was 31 months (range 0–77). Percentage of patients with RA, SpA, JIA and unspecified arthritis were 58,4%, 16,4%, 5,7%, and 19,5% respectively. Certolizumab-pegol was more used in RA (67% vs 49%) and JIA (8% vs 2%) while golimumab was more frequent among patients with SpA (21% and 12%) or PsA (23% and 10, respectively). Only 7% of golimumab and 10% of certulizumab-pegol patients received these drugs as first biologic treatment and approximately 50% of patients received these drugs as ≥3. biological treatment. In golimumab treated patients mean DAS28 decreased from 4,3 (baseline) to 3,3 (3 months); 2,8 (6 months) and 2,7 (12 months) but levelled off at 36 months follow up. Corresponding mean DAS28 levels in certulizumab-pegol treated patients were 4,6 (baseline); 3,2 (3 months); 2,8 (6 months) and 2,6 (12 months). The similar pattern was seen in changes in HAQ and CDAI over the study time. There were no statistically significant differences in DAS, HAQ or CDAI between treatments at any follow up visit. At the end of follow up 64 (38%) of golimumab and 60 (32%) of certulizumab-pegol patients remained on their treatment. No significant difference in drug survival was seen between the treatments (Figure). Patients with spondylartropathy had significantly better survival on golimumab compared to RA patients (p=0,005)whicih remained after adjustment for age, gender, CRP, number of previous biologics and concomitnt methotrexate at baseline. <h3>Conclusions</h3> Spondylarthropathy including psoriatic arthritis was associated with better drug survival on golimunab compared to certolizumab pegol. No other significant differences in efficacy, tolerability or drug survival were seen between golimumab and certolizumab pegol in patients with established arthritis in daily clinical practice. Approximately one third of patients starting these treatments remained on treatment after 3 years. <h3>Disclosure of Interest</h3> None declared

Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register

To study treatment response rates of RA patients undergoing second- and third-line anti-TNF therapy and to identify baseline predictors of response to second-line treatment. RA patients monitored in a prospective, observational study, having switched anti-TNF therapy once (first-time switchers, n = 337) or twice (second-time switchers, n = 36)--i.e. following failures with one antibody- and one receptor-type agent--between March 1999 and December 2006, were studied. Treatment responses at 3 months were assessed by the ACR and European League Against Rheumatism (EULAR) response criteria. Predictive potentials for response to second-line treatment of demographics, baseline disease activity measures, disease and treatment characteristics were analysed using logistic regression. ACR20 response was met by 51% of first-time and 35% of second-time switchers. Corresponding ACR50 rates were 27 and 18%; EULAR overall rates (EULAR good or moderate response) 71 and 58%; EULAR good rates 25 and 9% and 28-joint disease activity score (DAS28) remission rates 16 and 6%. Identified baseline predictors of response to second-line treatment were lower age and HAQ scores, elevated DAS28 values and having ceased the former anti-TNF treatment due to adverse events rather than inefficacy. No variable was predictive for all examined response criteria. Response rates of first-time anti-TNF switchers are somewhat below those of anti-TNF naïve RA patients, while the markedly inferior response rates of second-time switchers suggest other therapeutic options to be considered in this situation. Identified baseline predictors of response may be useful indicators to second-line anti-TNF therapy, but vary depending on the response criteria set studied.

Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register

To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences. Patients with active RA initiating their first treatment course of TNF-blocking therapy were enrolled. The study period was March 1999 through September 2006. The prospective protocol included information on demographics, clinical characteristics of patients and response measures. Fulfilment of ACR 50-70% improvement and European League Against Rheumatism (EULAR) good response or remission [28-joint disease activity score (DAS28) <2.6] at 3 months were chosen as primary outcome measures. Potential predictors of responses were identified using multivariate binary logistic regression models. In total, 1565 patients were included in the study. Gender did not influence treatment response. Consistently, concomitant methotrexate (MTX) was significantly associated with EULAR remission, EULAR good response, ACR50 response and ACR70 response with odds ratios (ORs) 1.97, 2.13, 2.10 and 1.75, respectively. Concurrent treatment with other DMARDs was also significantly associated with EULAR remission, EULAR good response and ACR50 response (OR: 1.96, 2.24 and 1.94, respectively). Likewise, low HAQ at baseline consistently predicted good clinical outcome. Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 (OR: 1.59 and 1.60, respectively), whereas DAS28 score at baseline was inversely associated with EULAR remission (OR: 0.78). In this observational study of patients with established RA, gender did not predict response to anti-TNF therapy, whereas treatment with concomitant DMARDs, especially MTX and low disability were associated with good response. Choice of outcome measures may influence the predictive value of baseline features.

Efficacy and tolerability of anti-tumour necrosis factor therapy in psoriatic arthritis patients: results from the South Swedish Arthritis Treatment Group register

Background:The use of tumour necrosis factor (TNF) blocking agents in psoriatic arthritis (PsA) is increasing, and the SSATG register has followed patients with PsA for more than 5 years. The...