D. van Zeben

Long-term course and outcome of functional capacity in rheumatoid arthritis: the effect of disease activity and radiologic damage over time.

OBJECTIVE To investigate the evolution of functional capacity, disease activity, and joint destruction over time in a 12-year prospective cohort of rheumatoid arthritis (RA) patients, and to study the relative contribution of disease activity and joint destruction to the loss of functional capacity. METHODS One hundred thirty-two female patients with recent-onset RA were assessed at 0, 3, 6, and 12 years of followup for functional capacity (Health Assessment Questionnaire [HAQ] score), disease activity (Disease Activity Score [DAS]), and joint destruction (Sharp score of radiologic damage). RESULTS The Sharp score deteriorated steadily over time, while the HAQ score and DAS showed a variable course. The DAS correlated strongly with the HAQ score throughout the disease course. The correlation between the Sharp score and the HAQ score was weak at study start, but became strong after 12 years. After 12 years of followup, disease activity was the main determinant of the HAQ score when entered in a multivariate analysis. CONCLUSION Functional capacity is strongly influenced by disease activity throughout the course of RA. Even in longstanding RA, disease activity proves to be the main determinant of the HAQ score for functional capacity.

Clinical and radiological efficacy of initial vs delayed treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis

Objectives: To compare the clinical and radiological efficacy of initial vs delayed treatment with methotrexate (MTX) and infliximab (IFX) in patients with recent onset rheumatoid arthritis (RA). Methods: In a post hoc analysis of the BeSt study (for Behandel Stratagieen, Dutch for treatment strategies), 117 patients who started initial MTX+IFX were compared with 67 patients who started MTX+IFX treatment after failing (disease activity score (DAS)>2.4; median delay to IFX: 13 months) on ⩾3 traditional DMARDs. If the DAS remained >2.4, the protocol dictated IFX dose increases to 6, 7.5 and 10 mg/kg. In case of a DAS ⩽2.4 for ⩾6 months, IFX was tapered and finally stopped. We aimed to correct for allocation bias using propensity scores. Functional ability was measured by the Health Assessment Questionnaire (HAQ), radiological progression by Sharp/van der Heijde scoring (SHS). Results: Baseline differences between the initial and delayed groups were no longer significant after propensity score adjustment. At 3 years after baseline, patients treated with initial MTX+IFX experienced more improvement in HAQ over time and were less likely to have SHS progression than patients treated with delayed MTX+IFX (p = 0.034). At 2 years after IFX initiation, more patients in the initial group compared with the delayed group could discontinue IFX after a good response (56% vs 29%, p = 0.008). Conclusions: The results of this post hoc analysis suggest that using MTX+IFX as initial treatment for patients with recent onset RA is more effective than reserving MTX+IFX for patients who failed on traditional DMARDs, with more HAQ improvement over time, more IFX discontinuation and less progression of joint damage.

Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial

Objectives To compare 1-year clinical efficacy of (1) initial triple disease-modifying antirheumatic drug therapy (iTDT) with initial methotrexate (MTX) monotherapy (iMM) and (2) different glucocorticoid (GC) bridging therapies: oral versus a single intramuscular injection in early rheumatoid arthritis. Methods In a single-blinded randomised clinical trial patients were randomised into three arms: (A) iTDT (methotrexate+sulfasalazine+hydroxychloroquine) with GCs intramuscularly; (B) iTDT with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. Primary outcomes were (1) area under the curve (AUC) of Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS) and (2) the proportion of patients with radiographic progression. Results 281 patients were randomly assigned to arms A (n=91), B (n=93) or C (n=97). The AUC DAS and HAQ were respectively −2.39 (95% CI −4.77 to −0.00) and −1.67 (95% CI −3.35 to 0.02) lower in patients receiving iTDT than in those receiving iMM. After 3 months, treatment failure occurred less often in the iTDT group, resulting in 40% fewer treatment intensifications. The difference in treatment intensifications between the arms required to maintain the predefined treatment goal remained over time. No differences were seen between the two GC bridging therapies. Respectively 21%, 24% and 23% of patients in arms A, B and C had radiographic progression after 1 year. Patients receiving iTDT had more adjustments of their medication owing to adverse events than those receiving iMM. Conclusions Treatment goals are attained more quickly and maintained with fewer treatment intensifications with iTDT than with iMM. However, no difference in radiographic progression is seen. Both GC bridging therapies are equally effective and, therefore, both can be used. Trial registration number ISRCTN26791028.

Patient-reported outcomes in a randomized trial comparing four different treatment strategies in recent-onset rheumatoid arthritis

OBJECTIVE To investigate the effectiveness of 4 different treatment strategies for recent-onset rheumatoid arthritis (RA) on 2-year patient-reported outcomes, including functioning and quality of life. METHODS A total of 508 patients with recent-onset RA were randomly assigned to 1) sequential monotherapy, 2) step-up combination therapy, both starting with methotrexate, 3) initial combination therapy, including a tapered high-dose prednisone, or 4) initial combination therapy with methotrexate and infliximab. Treatment was adjusted every 3 months if the Disease Activity Score (DAS) remained >2.4. The McMaster Toronto Arthritis Patient Preference Disability Questionnaire, the Short Form 36 (SF-36), and scores for pain, global health, and disease activity measured on a 100-mm visual analog scale (VAS) were compared between groups at baseline and every 3 months thereafter for 2 years. RESULTS After 2 years, all patient-reported outcomes had improved significantly from baseline, irrespective of the treatment strategy. SF-36 subscale scores approached population norms for 3 physical components, and achieved population norms (P > 0.05) for bodily pain and 4 mental components. Improvement in functioning, VAS scores, and physical items of the SF-36 occurred significantly earlier in patients treated with initial combination therapies (all comparisons after 3 months: overall P < 0.001; P < 0.05 for groups 1 and 2 versus groups 3 and 4). CONCLUSION All 4 DAS-driven treatment strategies resulted in substantial improvements in functional ability, quality of life, and self-assessed VAS scores after 2 years. Initial combination therapy led to significantly faster improvement in all patient-reported measures.

Association of Low Baseline Levels of Erythrocyte Folate With Treatment Nonresponse at Three Months in Rheumatoid Arthritis Patients Receiving Methotrexate

OBJECTIVE To investigate whether baseline concentrations of one-carbon metabolism biomarkers are associated with treatment nonresponse and adverse events in rheumatoid arthritis (RA) patients receiving methotrexate (MTX). METHODS A prospective derivation cohort (n = 285) and validation cohort (n = 102) of RA patients receiving MTX were studied. Concentrations of plasma homocysteine, serum vitamin B12 , serum folate, erythrocyte vitamin B6 , and erythrocyte folate were determined at baseline and after 3 months of treatment. Nonresponse after 3 months was assessed using the Disease Activity Score in 28 joints (DAS28) and the European League Against Rheumatism (EULAR) response criteria. Adverse events at 3 months were assessed using biochemical parameters and health status questionnaires. Analyses were corrected for baseline DAS28, age, sex, MTX dose, comedications, and presence of the methylenetetrahydrofolate reductase 677TT genotype. RESULTS In the derivation cohort, the mean DAS28 scores at baseline and 3 months were 4.94 and 3.12, respectively, and 78% of patients experienced adverse events. This was similar between the 2 cohorts, despite a lower MTX dose in the validation cohort. Patients with lower levels of erythrocyte folate at baseline had a higher DAS28 at 3 months in both the derivation cohort (β = -0.15, P = 0.037) and the validation cohort (β = -0.20, P = 0.048). In line with these results, lower baseline erythrocyte folate levels were linearly associated with a 3-month DAS28 of >3.2 in both cohorts (derivation cohort, P = 0.049; validation cohort, P = 0.021) and with nonresponse according to the EULAR criteria (derivation cohort, P = 0.066; validation cohort, P = 0.027). None of the other biomarkers (levels at baseline or changes over 3 months) were associated with the DAS28 or treatment nonresponse. Baseline levels of the biomarkers and changes in levels after 3 months were not associated with incidence of adverse events. CONCLUSION A low baseline concentration of erythrocyte folate is associated with high disease activity and nonresponse at 3 months after the start of MTX treatment and could be used in prediction models for MTX outcome. None of the investigated one-carbon metabolism biomarkers were associated with incidence of adverse events at 3 months.

Tapering conventional synthetic DMARDs in patients with early arthritis in sustained remission: 2-year follow-up of the tREACH trial

Objectives With early and intensive treatment many patients with early RA attain remission. Aims were to investigate (1) the frequency and time to sustained remission and subsequent tapering in patients initially treated with conventional synthetic disease modifying anti-rheumatic drug ((cs)DMARD) strategies and (2) the frequency and time to flare and regained remission in patients tapering csDMARDs and biological (b)DMARDs during 2 years of follow-up. Methods Two-year follow-up data from the treatment in the Rotterdam Early Arthritis Cohort (tREACH) cohort were used. Patients were randomised to initial treatment with triple DMARD therapy (iTDT) with glucocorticoid (GC) bridging or methotrexate monotherapy (iMM) with GC bridging. Patients were evaluated every 3 months. In case Disease Activity Score (DAS) was >2.4 treatment was switched to a TNF-blocker. In case DAS<1.6 at 2 consecutive time points, tapering was initiated according to protocol. Outcomes were rates of sustained remission (DAS<1.6 at 2 consecutive time points), flare (medication increase after tapering) and remission after flare (DAS<1.6). Data were analysed using Kaplan-Meier analyses. Results During 2 years of follow-up, sustained remission was achieved at least once by 159 (57%) of patients, of whom 118 and 23 patients initiated tapering of csDMARDs and bDMARDs, respectively. Thirty-four patients achieved drug-free remission. Flare rates were 41% and 37% and within 1 year, respectively. After flare, 65% of patients tapering csDMARDs re-achieved remission within 6 months after treatment intensification. Conclusions Regardless of initial treatment strategy, 57% of patients achieved sustained remission during 2 years of follow-up. Flare rates were 41% and 37% within 12 months in patients tapering csDMARDs and bDMARDs, respectively. Trial registration number ISRCTN26791028; Post-results.

SAT0111 Induction therapy with a combination of dmards is superior to methotrexate mono-therapy, unbiased for corticosteroids

Background The recently published EULAR treatment guideline recommended treatment for DMARD naïve patients is Methotrexate (MTX) with(out) glucocorticoids (GCs). Combination therapy with classical DMARDs however is not recommended, because well proven evidence of superior efficacy is suggested to be lacking. Furthermore possible drug toxicities might influence the physician’s choice of induction therapy. Objectives To compare the 3 month clinical efficacy of: (1) combination DMARD vs. MTX mono-therapy and (2) oral GCs bridging therapy vs. 1 dose of intramuscular (im) GCs in patients with early RA. Methods For this study data are used of a currently ongoing single-blinded randomized clinical trial in patients ≥18 years with recent-onset arthritis (tREACH). We included patients who had a high probability (>70%) according to their likelihood of progressing to persistent arthritis based of the prediction model of Visser. The Visser algorithm and 2010 criteria for RA have similar discriminative abilities to identify patients at risk of persistent arthritis at 1 year. Patients were randomized into 3 induction therapy strategies: (A) Combination therapy (MTX 25 mg/wk + SASP 2 gr./day + HCQ 400 mg/day) with GCs im (Depomedrol 120mg), (B) Combination therapy with an oral GCs tapering scheme (starting dose 15 mg) and (C) MTX with oral GCs similar to B. In case of “treatment failure”, defined as DAS>2.4, medication is intensified to MTX with a biological. Disease activity, functional ability, and adverse events were assessed. Results A total of 281 patients were randomly assigned to [A] (n=91), [B] (n=93) or [C] (n=97). Disease activity, after 3 months, was 0.39 (0.67–0.11, 95% CI) lower in patients with initial combination therapy compared to MTX mono-therapy. Difference in disease activity between the different GCs bridging therapies was 0.03 (–0.24–0.31, 95% CI). After three months 50% less biologicals were prescribed in the combination therapy groups. Functional ability (respectively 0.53 (0.40–0.66) [A] vs 0.53 (0.40–0.65) [B] vs 0.69 (0.55–0.84) [C]) and medication adjustments due to adverse events (resp. 22% [A] vs 20% [B] vs 16% [C]) did not differ between groups. Conclusions In patients with >70% chance of developing a RA a combination of DMARDs is superior to MTX mono-therapy in achieving low disease activity after three months, unbiased for GCs. Consequently 50% less biologicals were prescribed in the combination therapy groups. Furthermore intramuscular and oral GCs are equally effective as bridging therapy and can both be used. Funding Unrestricted grant from Pfizer bv. [0881-102217] Disclosure of Interest None Declared

Effects of psychosocial factors on monitoring treatment effect in newly diagnosed rheumatoid arthritis patients over time: response data from the tREACH study

Objectives: To investigate whether, apart from effects of patient- and disease-related factors, psychosocial factors have additional effects on disease activity; and which factors are most influential during the first year of treatment in early rheumatoid arthritis (RA). Method: The study assessed 15 month follow-up data from patients in tREACH, a randomized clinical trial comparing initial triple disease-modifying anti-rheumatic drug therapy to methotrexate monotherapy, with glucocorticoid bridging in both groups. Patients were evaluated every 3 months and treated to target. Associations between Disease Activity Score (DAS) at 3, 9, and 15 months and psychosocial factors (anxiety, depression, fatigue, and coping with pain) at the previous visit were assessed by multivariable linear regression correcting for demographic, clinical, and treatment-related factors. Results: At 3, 9, and 15 months of follow-up, 265, 251, and 162 patients, respectively, were available for analysis. Baseline anxiety and coping with pain were associated with DAS at 3 months; coping with pain at 6 months was associated with DAS at 9 months, and fatigue at 12 months with DAS at 15 months. Psychosocial factors were moderately correlated. Effects on DAS were mainly due to tender joint count and global health. Conclusion: Psychosocial factors have additional effects on DAS throughout the first year of treatment in early RA. A change was observed from anxiety and coping with pain at baseline being associated with subsequent DAS towards fatigue being associated with subsequent DAS at 12 months. Owing to the explorative nature of this study, more research is needed to confirm this pattern.

SAT0103 Three-monthly ultrasound monitoring of rheumatoid arthritis patients tapering their medication has limited value in predicting disease relapse

Background Prognostic factors that may guide tapering decisions for DMARDs and TNFi on individual patient level are not available. To improve successful tapering subclinical synovitis may play a role in maintaining the remission state. Studies using ultrasound suggest that the presence of subclinical synovitis may elicit early disease relapse in remission. Objectives Our aim is to determine if ultrasound synovitis precedes disease relapse while tapering synthetic DMARD (sDMARD) or TNFi in patients with RA who achieved clinical remission on sDMARD and TNFi. Methods We included 125 RA patients (aged>17 years) treated with an sDMARD and a TNF-inhibitor who were in remission (DAS44≤2.4 & SJC≤1). Demographic characteristics, swollen and tender joints, laboratory variables and ultrasound synovitis (MCP2-5; PIP2-5; wrists; MTP2-5) were recorded at each visit (every three months) during one year follow-up. Patients were randomised to two tapering strategies: i) tapering sDMARD; ii) tapering TNFi. Disease relapse was defined as DAS44>2.4 or SJC>1. Ultrasound synovitis was defined as GS≤1 and/or PD≤0. To estimate whether ultrasound is able to identify patients who will have a disease relapse within three months follow-up a Cox proportional regression model for time to event data was used. Results: Ultrasound synovitis was found in 58% of RA patients in clinical remission. After one year follow-up 36% of RA patients had a disease relapse of whom 60% had ultrasound synovitis at baseline. table 1 shows the distribution of relapse en ultrasound synovitis for every three months. In the multivariate Cox model increasing number of joints with ultrasound synovitis was not significantly associated with disease relapse within three months follow-up (HR 1.21; 95%CI: 0.97-1.51) [table 2].Table 1 Distribution of disease relapse and US synovitis during follow-up, n (%) T0 T3 T6 T9 T12 US synovitis 72/125 (58) 60/124 (48) 62/112 (55) 40/96 (42) - Disease relapse 0 6/124 (5) 8/112 (7) 23/96 (24) 8/67 (12) US synovitis at previous visit - 4/6 (67) 5/8 (63) 14/23 (61) 6/8 (75) No disease relapse 0 118/124 (95) 104/112 (93) 73/93 (78) 59/67 (88) No US synovitis at previous visit - 46/118 (39) 47/104 (45) 23/73 (32) 29/59 (49) US = ultrasound Table 2 Multivariate Cox model with US synovitis or PD synovitis for disease relapse Model US synovitis HR (95% CI) Model PD synovitis HR (95% CI) Age 0.99 (0.97-1.02) 0.99 (0.97-1.02) Gender 1.08 (0.53-2.17) 1.05 (0.53-2.11) Time since diagnosis 1.02 (0.92-1.13) 1.03 (0.93-1.14) ACCP 0.47 (0.24-0.91) 0.51 (0.27-0.97) DAS (at time of US) 2.25 (1.21-4.19) 2.34 (1.25-4.41) US synovitis 1.21 (0.97-1.51) PD synovitis 1.35 (1.02-1.80) US = ultrasound; PD = power Doppler; HR = hazard ratio; ACCP=anti-cyclic citrullinated peptide antibody; DAS = disease activity score Conclusions Monitoring RA patients who started tapering their medication every three months showed limited value for ultrasound to identify patients who will have a disease relapse. Disclosure of Interest: None declared