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.

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.

Achievement of Remission and Low Disease Activity Definitions in Patients with Rheumatoid Arthritis in Clinical Practice: Results from the NOR-DMARD Study.

OBJECTIVE: To examine the frequency of 6 definitions for remission and 4 definitions for low disease activity (LDA) after starting a disease-modifying antirheumatic drug (DMARD) in patients with rheumatoid arthritis (RA) in clinical practice, and to study whether predictors for achieving remission after 6 months are similar for these definitions. METHODS: Remission and LDA were calculated according to the 28-joint Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), the Routine Assessment of Patient Index Data (RAPID3), and both the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission definitions 3 and 6 months after 4992 DMARD prescriptions for patients enrolled in the NOR-DMARD, a 5-center Norwegian register. Prediction of remission after 6 months was also studied. RESULTS: After 3 months, remission rates varied between definitions from 8.7% to 22.5% and for LDA from 35.5% to 42.7%, and increased slightly until 6 months of followup. DAS28 and RAPID3 gave the highest and ACR/EULAR, SDAI, and CDAI the lowest proportions for remission. Positive predictors for remission after 6 months were similar across the definitions and included lower age, male sex, short disease duration, high level of education, current nonsmoking, nonerosive disease, treatment with a biological DMARD, being DMARD-naive, good physical function, little fatigue, and LDA. CONCLUSION: In daily clinical practice, the DAS28 and RAPID3 definitions identified remission about twice as often as the ACR/EULAR Boolean, SDAI, and CDAI. Predictors of remission were similar across remission definitions. These findings provide additional evidence to follow treatment recommendations and treat RA early with a DMARD.

No excess risks in offspring with paternal preconception exposure to disease-modifying antirheumatic drugs.

OBJECTIVE: To examine pregnancy outcomes in the partners of male patients with inflammatory joint disease who were or were not exposed to disease-modifying antirheumatic drugs (DMARDs) before conception compared with the outcomes in reference subjects from the general population. METHODS: Linkage of data from a longitudinal observational study of patients with inflammatory joint disease (the Norwegian Disease-Modifying Antirheumatic Drug [NOR-DMARD] registry study) and the Medical Birth Registry of Norway (MBRN) enabled a comparison of pregnancy outcomes in the partners of men with inflammatory joint disease. Outcomes of pregnancies in which the father was exposed to DMARDs within 12 weeks of conception and those in which the father was never exposed to DMARDs were analyzed separately and compared with the outcomes in reference subjects. Potential associations between DMARD exposure and adverse pregnancy outcomes were assessed by logistic regression analysis. RESULTS: A total of 1,796 men with inflammatory joint disease were associated with 2,777 births in the MBRN. In 110 of these births, the father had been exposed to DMARDs within 12 weeks before conception, and in 230 births the father had never been exposed to DMARDs before conception. The DMARDs (monotherapy or combination treatment) to which the fathers were exposed most frequently within 12 weeks of conception were methotrexate (n = 49), sulfasalazine (n = 17), and tumor necrosis factor inhibitors (n = 57). Neither adverse pregnancy outcomes nor occurrence of congenital malformations differed between patients and reference subjects in either group. CONCLUSION: Preconception paternal exposure to DMARDs was not associated with an increase in adverse pregnancy outcomes. Importantly, no increased risk of congenital malformations was observed.

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.

The role of methotrexate co-medication in TNF-inhibitor treatment in patients with psoriatic arthritis: results from 440 patients included in the NOR-DMARD study.

BACKGROUND: The role of co-medication with tumour necrosis factor inhibitors (TNFi) is well established in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis (PsA) there is little evidence available on this issue. MATERIAL AND METHODS: The analyses were based on data from the Norwegian longitudinal observational study on disease-modifying antirheumatic drugs (NOR-DMARD). Patients with PsA starting their first TNFi, either as monotherapy or with concomitant methotrexate (MTX), were selected. Baseline characteristics, responses after 3, 6 and 12 months, and drug survival were compared between those with and without MTX co-medication. A secondary analysis was performed on patients who had confirmed swollen joints at baseline. Cox regression was used to identify predictors of discontinuation. RESULTS: We included 440 patients, 170 receiving TNFi as monotherapy and 270 receiving concomitant MTX. The groups had similar baseline characteristics, except for number of swollen joints, which was higher in the concomitant MTX group. Responses were similar in the two groups in both analyses. Drug survival analyses revealed a borderline significant difference in favour of patients receiving co-medication (p=0.07), and this was most prominent for patients receiving infliximab (IFX) (p=0.01). In the Cox regression analysis lack of concomitant MTX and current smoking were independent predictors of discontinuation of TNFi. CONCLUSIONS: We found similar responses to TNFi in patients with and without concomitant MTX, but drug survival was superior in patients receiving co-medication. The effect of MTX on drug survival was most prominent in patients receiving IFX. Smoking at baseline and use of TNFi as monotherapy were identified as independent predictors of drug discontinuation.

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.

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.

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.