Exploring drug cost and disease outcome in rheumatoid arthritis patients treated with biologic and targeted synthetic DMARDs in Norway in 2010-2019 - a country with a national tender system for prescription of costly drugs.

BACKGROUND: In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system. METHODS: RA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process. RESULTS: The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019). CONCLUSIONS: In the period 2010-2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities' intention to reduce treatment costs by implementing a tender system has been successful.

Health-related quality of life in patients with psoriatic and rheumatoid arthritis: data from the prospective multicentre NOR-DMARD study compared with Norwegian general population controls.

OBJECTIVES: To compare (1) Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), scale scores and Short Form-6 dimensions (SF-6D) between patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) and Norwegian general population controls and (2) improvements in these measures between patients with RA and PsA. METHODS: Analyses of covariance were performed to compare SF-36 measures between first-time enrolled patients with RA (n=3898) and PsA (n=1515) from the prospective observational multicentre NORwegian-Disease Modifying Anti-Rheumatic Drug study (6 months follow-up) and general population controls (n=2323). RESULTS: In age and gender-adjusted analyses, patients with PsA compared with patients with RA had similar PCS, MCS and SF-6D (p≥0.14), worse vitality and general health, but better physical functioning at 0/6 months (p≤0.03). With additional 28-joint disease activity scores adjustment as a proxy for joint inflammation, PCS, most scale scores and SF-6D were worse in patients with PsA than patients with RA at 0/3/6 months (p≤0.01). PCS was more impaired than MCS both in RA and PsA compared with general population controls (p≤0.001). Mean 3-month and 6-month improvements after disease-modifying anti-rheumatic drug treatment were larger in patients with RA than patients with PsA for bodily pain, vitality and mental health (p≤0.02). CONCLUSIONS: Health-related quality of life was overall similar in patients with RA and patients with PsA-with a tendency to worse scores in PsA-and worse compared with Norwegian general population controls.

Discordance between tender and swollen joint count as well as patient's and evaluator's global assessment may reduce likelihood of remission in patients with rheumatoid arthritis and psoriatic arthritis: data from the prospective multicentre NOR-DMARD study.

OBJECTIVE: To investigate the predictive value of discordance between (1) tender and swollen joint count and (2) patient's and evaluator's global assessment on remission in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: From the prospective, multicentre Norwegian-Disease-Modifying Antirheumatic Drug study, we included patients with RA and PsA starting first-time tumour necrosis factor inhibitors and DMARD-naïve patients starting methotrexate between 2000 and 2012. The predictive value of ΔTSJ (tender minus swollen joint counts) and ΔPEG (patient's minus evaluator's global assessment) on remission was explored in prespecified logistic regression models adjusted for age, sex, disease duration and smoking. RESULTS: A total of 2735 patients with RA and 1236 patients with PsA were included (mean (SD) age 55.0 (13.5)/48.3 (12.4) years, median(range) disease duration 0.7 (0.0-58.0)/1.3 (0.0-48.3) years, 69.7/48.4% females). Baseline ΔTSJ/ΔPEG reduced the likelihood of achieving DAS28<2.6, SDAI≤3.3, CDAI≤2.8, ACR/EULAR Boolean and DAPSA<4 remission after 3 and 6 months in RA (OR 0.95-0.97, p<0.001/OR 0.96-0.99, p≤0.01) and PsA (OR 0.91-0.94, p≤0.004/OR 0.89-0.99, p≤0.002), except for ΔPEG and 6-month DAS28 remission in PsA. CONCLUSIONS: Discordance between patient's and physician's evaluation of disease activity reflected through ΔTSJ and partly ΔPEG may reduce likelihood of remission in RA and PsA. The findings are relevant for use of the treat-to-target strategy in individual patients.

Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR-DMARD study.

OBJECTIVE: To investigate the predictive value of baseline depression/anxiety on the likelihood of achieving joint remission in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as well as the associations between baseline depression/anxiety and the components of the remission criteria at follow-up. METHODS: We included 1326 patients with RA and 728 patients with PsA from the prospective observational NOR-DMARD study starting first-time tumour necrosis factor inhibitors or methotrexate. The predictive value of depression/anxiety on remission was explored in prespecified logistic regression models and the associations between baseline depression/anxiety and the components of the remission criteria in prespecified multiple linear regression models. RESULTS: Baseline depression/anxiety according to EuroQoL-5D-3L, Short Form-36 (SF-36) Mental Health subscale ≤56 and SF-36 Mental Component Summary ≤38 negatively predicted 28-joint Disease Activity Score <2.6, Simplified Disease Activity Index ≤3.3, Clinical Disease Activity Index ≤2.8, ACR/EULAR Boolean and Disease Activity Index for Psoriatic Arthritis ≤4 remission after 3 and 6 months treatment in RA (p≤0.008) and partly in PsA (p from 0.001 to 0.73). Baseline depression/anxiety was associated with increased patient's and evaluator's global assessment, tender joint count and joint pain in RA at follow-up, but not with swollen joint count and acute phase reactants. CONCLUSION: Depression and anxiety may reduce likelihood of joint remission based on composite scores in RA and PsA and should be taken into account in individual patients when making a shared decision on a treatment target.

First step in the development of an ultrasound joint inflammation score for rheumatoid arthritis using a data-driven approach.

OBJECTIVES: To develop and validate candidate sets of joints and tendons for assessment of ultrasound (US) joint inflammation in rheumatoid arthritis (RA). METHODS: Patients were included in one of two cohorts from 2010 to June 2013: disease-modifying antirheumatic drug naïve early RA or established RA starting/switching biologics. An extensive US examination was performed by experienced sonographers using a validated grey-scale (GSUS) and power Doppler (PDUS) semiquantitative scoring system with scores 0-3 for both GSUS and PDUS in 36 joints and four tendons. We performed factor analysis in the early RA US data and selected candidate joint/tendon sets based on these results. The proportion of information in the total US scores retained in these candidate sets was assessed by R(2) from linear regression analysis. Finally, the candidate sets and previously proposed joint scores were tested in the established RA cohort, and we also evaluated the sensitivity to change with standardised response means. RESULTS: 227 patients with early RA and 212 patients with established RA were included. We identified two candidate sets of joints/tendons: candidate set A consisted of seven joints/two tendons (meatacarpophalangeal 1 (MCP1), MCP2, proximal interphalangeal 3, radiocarpal, elbow, metatarsophalangeal 1 (MTP1), MTP2, tibialis posterior tendon, extensor carpi ulnaris tendon) and set B of nine joints/two tendons (MCP5 and MTP5 added to set A). Unilateral reduced scores retained 78%-85% of the information in total score, while bilateral reduced scores retained 89%-93%, and both sets performed better than previously proposed reduced joint scores, and similar or slightly better regarding sensitivity to change. CONCLUSIONS: The reduced GSUS and PDUS scores retained most of the information from the total score and performed well in a validation cohort of established RA. TRIAL REGISTATION NUMBER: NCT01205854, ACTRN12610000284066.

Time trends in disease activity, response and remission rates in rheumatoid arthritis during the past decade: results from the NOR-DMARD study 2000-2010.

OBJECTIVES: To investigate whether baseline disease activity levels and responses in patients with rheumatoid arthritis (RA) changed during the period 2000-2010. METHODS: Data were provided by the Norwegian disease-modifying antirheumatic drug (NOR-DMARD) study. Patients with inflammatory joint diseases starting new treatment with disease-modifying antirheumatic drugs (DMARDs) were consecutively included and followed longitudinally. Time trend analyses were performed in methotrexate (MTX)-naïve RA patients starting MTX monotherapy (MTX mono) and biologic DMARD (bDMARD)-naïve RA patients starting tumour necrosis factor inhibitors+MTX (TNFi+MTX). RESULTS: A total of 2573 patients were included in the analyses: MTX mono n=1866 (69.9% female, 62.0% RF+, mean (SD) age 56.0 (13.7) years, median (25-75 percentile) time from diagnosis 0.2 (0.01-2.8) years); TNFi+MTX n=707 (70.3% female, 75.0% RF+, mean (SD) age 52.1 (13.2) years, median (25-75 percentile) time from diagnosis 5.7 (2.0-13.7) years). Significant time trends towards lower baseline disease activity score 28 (DAS28) as well as other disease activity measures were found in both groups (DAS28 from 5.17 to 4.75 in MTX mono and from 5.88 to 4.64 in TNFi+MTX), and disease duration became shorter. Six-month DAS28 remission rates increased significantly over the years (from 17.8 to 37.6 in MTX mono and from 16.9 to 46.3 in TNFi+MTX). CONCLUSIONS: During the last decade, baseline RA disease activity level at the time of starting MTX as well as TNFi+MTX decreased from high to moderate. A more than twofold increase in 6-month remission rates was observed in both groups. Our findings indicate that clinicians have implemented modern, more aggressive treatment strategies, which hopefully will lead to better long-term disease outcomes.

Is there a role for sulphasalazine in axial spondyloarthritis in the era of TNF inhibition? Data from the NOR-DMARD longitudinal observational study.

OBJECTIVES: The objectives of this study were to characterize patients with predominantly axial SpA who received SSZ as their first DMARD, compare the response to treatment in patients with and without peripheral disease and identify predictors of discontinuation of SSZ. We also investigated response to TNF inhibitor (TNFi) after SSZ failure. METHODS: We included DMARD-naive patients with predominantly axial SpA starting SSZ or TNFi treatment from a Norwegian, multicentre longitudinal observational study (NOR-DMARD). In patients starting SSZ, we compared the 3-month responses between patients with and without swollen joints and identified predictors of discontinuation by Cox regression analysis. Sixty-six SSZ-treated patients later switched to a TNFi, and we compared their 3-month responses and drug survival to patients starting a TNFi as their first DMARD. RESULTS: Patients receiving SSZ (n = 181) as their first DMARD had shorter disease duration, were more frequently female and had more swollen joints than those starting TNFi (n = 543). There was a trend toward better 3-month responses to SSZ in patients with peripheral joint swelling, and they had significantly better 3-year drug survival than patients without swollen joints at baseline. Predictors of SSZ discontinuation were no peripheral joint swelling, higher CRP and higher BASDAI back pain score. TNFi response was similar in patients previously treated with SSZ, as in DMARD-naive patients. CONCLUSION: Our findings support current recommendations of SSZ as an optional treatment in SpA patients with peripheral disease, although overall responses were modest. Initial treatment with SSZ does not seem to impair later TNFi response.

Patient satisfaction with nursing consultations in a rheumatology outpatient clinic: a 21-month randomised controlled trial in patients with inflammatory arthritides.

OBJECTIVE: To study the effect of individual nursing consultations in patients treated with disease-modifying antirheumatic drugs (DMARDs) in a rheumatology outpatient setting. METHODS: Patients with inflammatory arthritides (IA) who had started with a DMARD regimen 3 months before were randomised to two different follow-up consultation systems: either follow-up by a clinical nurse specialist (CNS) or by a medical doctor (MD) in rheumatology 3, 9 and 21 months after randomisation. The primary outcome was patient satisfaction measured by Leeds Satisfaction Questionnaire (LSQ). Secondary outcomes included coping, disease activity, pain, fatigue, patient's global assessment of disease activity and health related quality of life. Effects at 9 and 21 months were estimated by Least Square means calculated from the final mixed model. RESULTS: Of 68 patients randomised, 65 patients completed assessments at 21 months. Statistically significant improvements in favour of the CNS group were found in all LSQ subscales (all p values<0.001) and in overall satisfaction at 9 months (adjusted mean between-group difference 0.74, 95% CI -0.96 to -0.52) and at 21 months (-0.69, 96% CI -0.87 to -0.50). Disease activity Score 28 joint count (DAS-28) was improved from baseline to 9 months in both groups and improvement was maintained at 21 months, but without any group difference. No statistically significant between-group differences were found in any of the other secondary outcomes. CONCLUSIONS: Patients with IA are likely to benefit from nurse consultations in terms of increased satisfaction with care compared with MD consultations and without loss of efficacy in terms of clinical outcomes. The study is registered as a clinical trial at the ClinicalTrials.gov (NCT00403676).

Switching between TNF inhibitors in psoriatic arthritis: data from the NOR-DMARD study.

BACKGROUND: Tumour necrosis factor inhibitors (TNFi) are efficacious in patients with psoriatic arthritis (PsA), but some patients do not respond or do not tolerate their first TNFi, and are switched to a different TNFi. Evidence supporting this practice is limited, and we wanted to investigate the effectiveness of switching to a second TNFi. MATERIAL AND METHODS: From a longitudinal observational study (LOS) we selected patients with PsA who were starting their first TNFi, and identified patients who had switched to a second TNFi ('switchers'). Three-month responses and 3-year drug-survival were compared between switchers and non-switchers, and within switchers. RESULTS: Switchers (n=95) receiving their second TNFi had significantly poorer responses compared with non-switchers (n=344) (ACR50 response: 22.5% vs 40.0%, DAS28 remission: 28.2% vs 54.1%). There was a trend towards poorer responses to the second TNFi compared with the first TNFi within switchers. Estimated 3-year drug-survival was 36% for the second TNFi compared with 57% for the first TNFi overall. CONCLUSIONS: 20-40% of patients had a response on a second TNFi after having failed one TNFi in this LOS. This observation highlights the need for treatments with other mechanisms of action than TNF inhibition in patients with PsA.

Effectiveness and Persistence in SB4- and Reference Etanercept-Treated Rheumatoid Arthritis Patients in Ordinary Clinical Practice in Norway.

OBJECTIVE: Biosimilars represent cost-effective alternatives to reference biologic disease-modifying antirheumatic drugs. Our objective was to compare drug effectiveness and drug persistence in the treatment of rheumatoid arthritis (RA), assessing the etanercept biosimilar SB4 in efficacy and safety compared with reference etanercept in a Phase III, randomized controlled trial. We applied EULAR Points to Consider for Comparative Effectiveness Research in a retrospective database study of etanercept and SB4 in patients treated in clinical practice in Norway. METHODS: Patients with RA (n = 1,455) treated with etanercept or SB4 between 2010 and 2018 at 5 centers in Norway with ≥1 year of follow-up were included. Disease outcomes (Disease Activity Score in 28 joints [DAS28] at week 52) and drug persistence were compared between unmatched etanercept (n = 575) and SB4 (n = 299) cohorts and matched analyses (n = 172, both cohorts) using propensity score (PS) matching to adjust for confounders. RESULTS: In unmatched analyses, the difference in change from baseline between etanercept (n = 221) and SB4 (n = 106) for DAS28 at week 52 was mean -0.02 (95% confidence interval [95% CI] -0.32, 0.27), demonstrating equivalence by the predetermined equivalence margin (±0.6). In PS-matched analyses, the difference between etanercept (n = 49) and SB4 (n = 49) was 0.03 (95% CI -0.46, 0.52), within the predefined equivalence margin. Persistence using the drug at week 52 was similar between etanercept (0.62 [95% CI 0.57, 0.65]) and SB4 (0.66 [95% CI 0.60, 0.71]) cohorts in the unmatched analysis; in PS-matched cohorts, persistence at week 52 was 0.52 (95% CI 0.44, 0.59) for etanercept and 0.68 (95% CI 0.61, 0.75) for SB4. CONCLUSION: Outcomes for disease status/drug persistence at week 52 were similar between patients with RA treated with etanercept or SB4.

Selecting patients with ankylosing spondylitis for TNF inhibitor therapy: comparison of ASDAS and BASDAI eligibility criteria.

OBJECTIVE: To compare Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1 with BASDAI >4 as an eligibility criterion for initiation of TNF inhibitor (TNFi) treatment in AS, and to investigate if ASDAS performs satisfactorily in patients without elevated CRP or without peripheral joint swelling. METHODS: Two hundred and eighty-nine patients starting their first TNFi were identified from a longitudinal observational study (NOR-DMARD) and grouped according to the fulfilment of ASDAS and BASDAI TNFi eligibility criteria. The 3-month responses were compared across several response measures. Patients were also grouped according to CRP level and the presence or absence of swollen joints, and responses were compared. RESULTS: The majority of patients (n = 212) fulfilled both eligibility criteria, and this group had the best response. Very few patients (n = 4) fulfilled only the BASDAI criterion. Patients fulfilling only the ASDAS criterion (n = 48) had a reasonable response. Patients with an elevated vs not elevated CRP at baseline had better responses according to all response measures, but patients without elevated CRP also responded. We also observed trends towards better responses in patients with vs without peripheral joint swelling. CONCLUSION: More patients were eligible for TNFi using the ASDAS than the BASDAI eligibility criterion (n = 260 vs n = 216). Fulfilment of both criteria gave the greatest likelihood of improvement, but the patients who only fulfilled the ASDAS criterion also improved. ASDAS was found to be applicable also in subgroups without elevated CRP and without peripheral joint swelling.

Effectiveness of sulfasalazine and methotrexate in 1102 DMARD-naive patients with early RA.

OBJECTIVE: To compare baseline characteristics, responses and drug survival in patients with early RA starting SSZ or MTX in a real-life setting. METHODS: The analyses included DMARD-naïve patients with RA (disease duration ≤ 1 year) starting SSZ or MTX. Three- and 6-month effectiveness was compared by unadjusted analysis and with adjustment for propensity score quintile. In addition, effectiveness in SSZ- and MTX-treated patients matched for RF status and baseline DAS-28 was compared. RESULTS: SSZ-treated patients (n = 175) had lower baseline disease activity than patients treated with MTX (n = 927) [mean 28-joint DAS (DAS-28) 4.4 vs 5.0, P < 0.001], and were less often RF positive (50 vs 61%, P = 0.006). Six-month mean ΔDAS-28 was smaller with SSZ than MTX (-1.0 vs -1.5, P = 0.003); the difference was not significant after adjustment for propensity score quintile (P = 0.36). For SSZ/MTX, 3-month ACR50 and European League Against Rheumatism (EULAR) good responses were 9/23% (P < 0.001) and 24/31% (P = 0.14), respectively. Three-year drug survival was superior for MTX (P < 0.001) and estimated 1-year survival rates were 42/75% for SSZ/MTX. In patients matched for baseline DAS-28 and RF, mean ΔDAS-28 (MTX -1.2, P = 0.55 vs SSZ) and EULAR good responses (39 vs 37%, P = 0.74) were similar at 6 months; drug survival was superior for MTX (P < 0.001). CONCLUSION: Patients treated with SSZ as first DMARD were more often RF negative and had lower baseline disease activity. Drug survival was superior for MTX, and effectiveness was greater with MTX than with SSZ although the difference was reduced when adjusting for differences in baseline characteristics.

Norwegian society of rheumatology recommendations on diagnosis and treatment of patients with giant cell arteritis.

Objective: To provide clinical guidance to Norwegian Rheumatologists and other clinicians involved in diagnosing and treating patients with giant cell arteritis (GCA). Methods: The available evidence in the field was reviewed, and the GCA working group wrote draft guidelines. These guidelines were discussed and revised according to standard procedures within the Norwegian Society of Rheumatology. The European Alliance of Associations for Rheumatology (EULAR) recommendations for imaging and treatment in large vessel vasculitis and the British Society for Rheumatology (BSR) guidelines for diagnostics and treatment in GCA informed the development of the current guidelines. Results: A total of 13 recommendations were developed. Ultrasound is recommended as the primary diagnostic test. In patients with suspected GCA, treatment with high doses of Prednisolone (40-60 mg) should be initiated immediately. For patients with refractory disease or relapse, Methotrexate (MTX) should be used as the first-line adjunctive therapy, followed by tocilizumab (TCZ). Conclusion: Norwegian recommendations for diagnostics and treatment to improve management and outcome in patients with GCA were developed.

Treatment strategies in patients with rheumatoid arthritis for whom methotrexate monotherapy has failed: data from the NOR-DMARD register.

OBJECTIVES: To compare the effectiveness of adding synthetic disease-modifying antirheumatic drugs (sDMARDs) versus tumour necrosis factor α inhibitors (TNFi) to methotrexate (MTX) in patients with rheumatoid arthritis (RA) who were MTX inadequate responders (IR). Second, to examine outcomes in patients receiving MTX+TNFi for whom the MTX+sDMARD combination had also failed. METHODS: Patients with RA (disease duration ≤ 5 years, MTX IR and naïve to other DMARDs) starting treatment with MTX+TNFi or MTX+sDMARDs were included. From the latter group a subgroup of patients who went on to receive MTX+TNFi was identified. RESULTS: Patients receiving MTX+TNFi (n=98) and MTX+sDMARDs (n=129) had similar baseline disease activity when starting combination therapy (mean Disease Activity Score 28 (DAS28) = 4.90 and 4.96, respectively). Three- and 6-month effectiveness and 2-year drug survival were better for MTX+TNFi than for MTX+sDMARDs: mean DAS28 was -1.61 versus -0.85 after 3 months (p<0.001) and -1.91 versus -1.03 after 6 months (p=0.01); DAS28<2.6 was reached by 29.0% versus 11.6% after 3 and 34.5% versus 12.9% after 6 months. Effectiveness was somewhat better with triple therapy than other MTX+sDMARD combinations but was generally inferior compared with MTX+TNFi. For the patients who received MTX+TNFi as a third step after MTX+sDMARDs had failed (n=38) there was a tendency towards lower remission rates, worse disease activity states and inferior drug survival compared with patients who received MTX+TNFi directly after the failure of MTX. CONCLUSIONS: Effectiveness was better for MTX+TNFi than for MTX+sDMARDs. Patients who started MTX+TNFi after two synthetic DMARD regimens had failed had a tendency to less favourable disease states after 3 months than patients who switched directly from MTX to MTX+TNFi.

Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis.

OBJECTIVE: To examine the effectiveness and 2-year retention rates of methotrexate (MTX) in MTX naïve patients with psoriatic arthritis (PsA). METHODS: Data on 430 patients with PsA participating in an ongoing longitudinal observational multicentre study in Norway were analysed. 1218 MTX naïve patients with rheumatoid arthritis (RA) from the same study served as a reference population. Assessments included measures of disease activity (28 joint counts, acute phase reactants), health status and utility scores. Six-month effectiveness data were compared both by crude analyses and with adjustments for age, sex and the respective baseline values. Two-year drug survival was compared by Kaplan-Meier and Cox regression analyses. RESULTS: After 6 months of MTX treatment, both patients with PsA and those with RA improved in most disease activity measures and patient reported outcomes. In the adjusted analysis, patients with PsA tended to have less improvement, but changes were in the same range as in patients with RA. Two-year retention rates of MTX therapy in patients with PsA and RA were 65% and 66%, respectively, with only minor differences in reported reasons for discontinuation. Lower age, longer disease duration and higher Modified Health Assessment Questionnaire (MHAQ) score and patient global assessment were independent predictors of MTX termination within the first 2 years of treatment. CONCLUSION: In this real-life study, MTX treatment was associated with improvement in disease activity and health-related quality of life in patients with PsA after 6 months of treatment. Retention rates of MTX were similar in PsA and RA.

Four-year follow-up of inflammatory arthropathy patients treated with golimumab: Data from the observational multicentre NOR-DMARD study.

OBJECTIVE: To compare (1) golimumab drug survival and efficacy in bDMARD naïve compared with non-naïve rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA) patients, (2) golimumab drug survival in RA and PsA patients treated with/without concomitant csDMARDs, (3) predictors of golimumab drug discontinuation. METHODS: Patients starting golimumab were included from the prospective observational multicenter Norwegian DMARD study. Drug survival was explored by Kaplan-Meier analyses with log rank test. Treatment responses were compared using ANCOVA. Univariate and multivariate Cox regression analyses were performed to identify predictors of golimumab discontinuation. RESULTS: We included 808 patients (163 RA, 266 PsA, 379 ax-SpA). Golimumab drug survival after 1/2/4 years were not significantly different between bDMARD naïve and non-naïve patients (all, p ≥ 0.12; RA, p ≥ 0.07; PsA, p ≥ 0.28; ax-SpA, p ≥ 0.61), nor between RA (p ≥ 0.10) and PsA (p ≥ 0.07) patients treated with vs. without csDMARD comedication. bDMARD naïve compared with non-naïve ax-SpA patients had better 3-month ASDAS/BASDAI/MHAQ responses (p ≤ 0.02). bDMARD naïve compared with non-naïve RA and PsA patients had a trend towards better treatment responses. Identified predictors of 4-year golimumab discontinuation were patient's global and female gender in patients overall and in subgroups of PsA and ax-SpA patients, and patient's global and CRP in RA. CONCLUSION: Golimumab drug survival was not significantly different between bDMARD naïve and non-naïve RA, PsA and ax-SpA patients, nor between RA and PsA patients treated with vs. without concomitant csDMARDs. Treatment responses were significantly better for bDMARD naïve than non-naïve ax-SpA patients. Identified predictors of golimumab discontinuation were patient's global and female gender in patients overall and in subgroups of PsA and ax-SpA patients, and patient's global and CRP in RA.

Does Older Age have an Impact on Rituximab Efficacy and Safety? Results from the NOR-DMARD Register.

OBJECTIVE: The objective of this study was to compare the efficacy and safety of rituximab in older vs younger patients with rheumatoid arthritis. METHODS: Data on 367 patients with rheumatoid arthritis treated with rituximab in the Norwegian Disease-Modifying Antirheumatic Drug (NOR-DMARD) register were analysed, comparing patients aged ≥ 65 years (n = 91) with patients aged < 65 years (n = 276). Drug survival was compared using a Kaplan-Meier analysis and Cox proportional hazard models. Disease activity, as assessed by the Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR) and the Simplified Disease Activity Index, was analysed with linear mixed models. The occurrence of adverse events was analysed by quasi-Poisson regression models. RESULTS: Drug survival was similar in the two age groups. The proportion of patients who remained taking rituximab over 2 years was 72% in those under aged 65 years vs 74% in those aged ≥ 65 years. No statistically significant association with age was found for drug survival in either the unadjusted (hazard ratio 1.13, p = 0.65) or adjusted Cox proportional hazard analyses for the model with DAS28-ESR as a confounder (effect size 1.11, p = 0.73). Models including the Simplified Disease Activity Index instead of DAS28-ESR yielded similar results. Age was furthermore not significantly associated with disease activity over time, although there was a tendency towards a poorer response in older patients. In the older age group, there was a higher incidence of pneumonia (107 vs 51 per 1000 patient-years) and other serious infections (142 vs 66 per 1000 patient-years). CONCLUSIONS: Rituximab is a reasonable therapeutic option for older patients with rheumatoid arthritis although vigilance is needed with regard to the infection profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01581294.

Treat to target strategy in early rheumatoid arthritis versus routine care - A comparative clinical practice study.

OBJECTIVE: To assess the 2-year effect on disease activity and health-related quality of life (HRQoL) of implementing a clinical practice treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA). METHODS: Patients in the Norwegian Very Early Arthritis Cohort 2.0 (NOR-VEAC 2.0), included 2010-2015, were treated according to T2T principles with visits at baseline, 3, 6, 9, 12 months, then every 6 months plus monthly visits until DAS28 <2.6. These patients were compared to a pre-T2T cohort of patients included in the Norwegian Disease Modifying Anti-Rheumatic Drug (NOR-DMARD) register 2006-2009. Both groups had a clinical diagnosis of RA (≤1 year) and were DMARD naïve. Disease activity and HRQoL outcomes were analysed, and the primary outcome was SDAI remission (≤3.3) at 2years. RESULTS: The T2T cohort included 293 patients (mean (SD) age 54 (13) years, 66% females, disease duration median (25,75 perc) 98 (57,164) days) and the routine care cohort 392 patients (age 54 (13) years, 68% females, 4 (0,30) days since diagnosis). At 2years, the proportion of patients achieving SDAI remission was 46% in the T2T cohort compared to 31% in the routine care cohort. EQ-5D was similar at baseline, but differed significantly between groups at 2years (median (25,75 perc) 0.77 (0.69, 0.85) vs 0.73 (0.59, 0.80), p < 0.001). Methotrexate monotherapy was the dominant DMARD regimen used to achieve SDAI remission in both cohorts. CONCLUSION: Higher remission rates and better HRQoL were achieved in patients following a T2T strategy in clinical practice compared to routine care.

Predicting achievement of the treatment targets at 6 months from 3-month response levels in rheumatoid arthritis: data from real-life follow-up in the NOR-DMARD study.

OBJECTIVE: When initiating a new therapy in patients with rheumatoid arthritis (RA), current treatment recommendations suggest escalating therapy in case of poor clinical improvement by 3 months or if the treatment target has not been reached by 6 months. We investigated which disease activity improvement levels at 3 months predicted achievement of the treatment targets at 6 months in a real-life clinical setting. METHODS: We included 1610 patients with RA enrolled in the NOR-DMARD study between 2000 and 2012. Analyses were performed for the total group of patients and repeated for subgroups stratified by baseline disease activity, disease duration or treatment with methotrexate or a tumour necrosis factor inhibitor. We used a diagnostic test approach to explore the associations between 3-month response and 6-month outcome. RESULTS: Not achieving 50% improvement in Simplified Disease Activity Index (SDAI) by 3 months significantly decreased the likelihood of reaching remission at 6 months in all subgroups (negative likelihood ratios (LRs-) 0.15-0.36). Patients with high disease activity when initiating treatment were likely to fail reaching remission if they achieved less than SDAI 70% response by 3 months (LR- 0.25 and negative predictive value 0.98). Achieving a major response (SDAI 85%) at 3 months significantly increased the likelihood of reaching remission at 6 months (LRs+ 6.56). CONCLUSION: Levels of 3-month disease activity improvement can inform clinicians when deciding to continue or adjust ongoing therapy in a treat-to-target strategy aiming for remission or low disease activity within 6 months. The required levels of 3-month improvement varied with baseline disease activity.