Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb < 100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenuous efforts should have been made to control the disease itself.

BackgroundPsoriatic arthritis (PsA) is a chronic inflammatory disorder associated with skin and joint manifestations, several extra-articular symptoms, various comorbidities, and disability. The emergence of tumour necrosis factor inhibitor (TNFi) therapy has dramatically changed the course of disease. Over the past decade new TNFi therapies have emerged (certolizumab pegol and golimumab), and recently ustekinumab and secukinumab have also become available for PsA.ObjectivesThe objective of this study was to assess the relative use of biological agents (bDMARDs) in PsA from 2006 through 2014, using data from the Nordic Rheumatology registers.MethodsBased on data from the observational registers DANBIO, ICEBIO, NOR-DMARD, ROB-FIN, and SRQ registers, PsA patients initiating treatment with bDMARDs as a first or subsequent biological therapy were identified. Adalimumab, etanercept and infliximab were grouped as “first generation TNFi therapies”; certolizumab pegol and golimumab were grouped as “second generation TNFi”. Treatments with ustekinumab during the study period were also identified. Descriptive statistics for prescription patterns of bDMARD therapy were calculated.ResultsA total of 11,458 treatment initiations were identified (DANBIO 3,068, ICEBIO 357, NOR-DMARD 1,113, ROB-FIN 708, SRQ 6,212). 54% of the patients were female. Overall, 5,695 patients initiated a first generation TNFi, 912 a second generation TNFi, and 16 ustekinumab, as their first course of biological treatment. The corresponding numbers for those initiating a second (or more) biological treatment were 3,606, 1,090 and 139 patients, respectively. The figure displays the annual number of treatment initiations stratified by treatment type. The total yearly number of first course biological treatment increased significantly throughout the period (p<0.001), and this was also the case for patients switching therapy (p<0.001), indicating a previously unmet need for biological therapies in the Nordic population. The annual number of patients initiating first generation TNFi both as first and subsequent course of therapy decreased significantly towards the end of the study period (p<0.001). This drop was more than offset by a rapid increase in initiation of second generation TNFi treatments (p<0.001). Ustekinumab was primarily used as second or subsequent course of therapy in PsA. The same pattern was seen when stratified for country (data not shown).ConclusionsAcross the Nordic countries the prescription pattern for biological therapies for PsA has changed significantly over time. After 2012 initiation of the first generation TNFi is decreasing both as first and second course therapy, whereas second generation TNFi are increasing both as first and second course of biologic intervention. Collaboration across registers will allow for robust assessment of the uptake of newer biological therapies.AcknowledgementsThis study was partly funded by a grant from NordForsk and Janssen Pharmaceuticals.Disclosure of InterestT. S. Jørgensen Speakers bureau: Abbvi...

BackgroundTocilizumab (TCZ) as monotherapy has been shown to be more efficacious than the TNF inhibitor (TNFi) adalimumab as monotherapy in patients with rheumatoid arthritis (RA). However, effectiveness data comparing TCZ as monotherapy versus TNF inhibitors in combination with csDMARDs are limited.ObjectivesTo examine retention of TCZ administered alone (TCZ mono) versus TNFi in combination with csDMARDs (TNFi combo) in patients with RA who had an inadequate response to ≥1 TNFi (TNFi-IR).MethodsPatients with RA who were TNFi-IR and treated with TCZ mono or TNFi combo with baseline (BL) data, not immediately lost to follow-up and started treatment after TCZ was available across 9 European registries in TOCERRA from 2009 to 2016 were included. The hazard for TCZ discontinuation was modeled using a country-stratified Cox proportional hazards model, adjusting for age, gender, disease duration, seropositivity, HAQ and CDAI at BL, number of previous csDMARD and biologic DMARD (bDMARD), glucocorticosteroid and calendar year of treatment initiation. Missing data on covariates were imputed using multiple imputation with chained equations.ResultsA total of 4748 patients were eligible, including 585 who received TCZ mono and 4163 who received TNFi combo. Patients who received TCZ mono were older with a longer disease duration, more previous bDMARDs and less glucocorticosteroids at baseline (Table 1) compared with patients who received TNFi combo. The crude median retention for TCZ mono was 1.82 years (95% CI: 1.59–2.09) and 1.54 years (95% CI: 1.43–1.64) for TNFi combo, (P=0.65). Causes of discontinuation differed between TCZ mono and TNFi combo (P<0. 001): TCZ mono stopped more frequently for ineffectiveness (25.7% vs. 13.8%) and TNFi combo stopped more frequently for safety issues (18.3% vs. 12.8%). In a country-stratified, covariate-adjusted analysis, we found that hazards of discontinuation were significantly lower among patients who received TCZ mono (HR: 0.71, P<0.001). More previous treatment with bDMARDs and a greater HAQ and CDAI at BL were significantly associated with greater risk of discontinuation.ConclusionsIn routine care across 9 European countries, TCZ mono retention is better than TNFi combo in patients with RA who were TNFi-IR.AcknowledgementsFunding by F. Hoffmann-La Roche/Genentech.Disclosure of InterestK. Lauper: None declared, D. Nordström Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, MSD, Roche, UCB and Pfizer, K. Pavelka Grant/research support from: AbbVie, Roche, Medis, MSD and Pfizer, Consultant for: AbbVie, Roche, Amgen, MSD, BMS, UCB and Egis, V. Hernandez: None declared, M. J. Santos: None declared, Z. Rotar: None declared, F. Iannone: None declared, C. Codreanu: None declared, G. Lukina Consultant for: BMS, Roche, MSD, AbbVie and Pfizer, S. Gale Employee of: Genentech, K. Sarsour Employee of: Genentech, A. Pethoe-Schramm Employee of: F. Hoffmann-La Roche, D. Courvoisier: None declared, C. Gabay Grant/research support from: AB2 Bio, AbbVie, ...

Objectives: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). Method: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. Results: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). Conclusion:In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.

Background Predictors of response to biologic therapy in rheumatoid arthritis (RA) are needed to achieve a more individualized therapy. Seropositivity has been associated with better response to rituximab (RTX). Objectives To assess the 6-month response to the first RTX course in RA according to RF and ACPA status. Methods Ten European registries submitted anonymized datasets from RA patients who had started RTX, and datasets were pooled and analysed. Chi-square test for comparison of categorical variables and t-test for continuous data were used. Predictors of response were identified by logistic regression analysis. Results 3266 patients were included in the cohort. 79.9% of patients were RF (+) (2041 out of 2553) and 73.2% were ACPA (+) (877 out of 1198). 718 patients were double positive (DP) and 147 double negative (DN). 2200 patients were RF (+) and/or ACPA (+). Improvements of DAS28 (ΔDAS28) at 6 months were significantly better for RF (+) than RF (–) patients as well as for ACPA (+) than ACPA (–), DP vs. DN and RF and/or ACPA (+) vs. DN (table 1). A significantly higher percentage of ACPA (+) and DP patients achieved EULAR Good Response at 6 months compared to ACPA (–) and DN, respectively (table 1). The completeness of data was very similar for seropositive and seronegative patients, with the percentage of missing data at 6 months being approximately 50% in all groups. A significantly higher percentage of seronegative patients received retreatment by 6 months than seropositive patients. In univariate analyses adjusted for age and gender ACPA positivity (OR=2.03, p=0.016) and DP (OR=2.43, p=0.03) but not RF positivity (OR=1.53, p=0.07) predicted EULAR good response to therapy with RTX at 6 months after the first treatment. Table 1. Clinical outcomes at 6 months for RTX treated patients according to RF and ACPA status RF (+)RF (–)p-valueACPA (+)ACPA (–)p-value Baseline DAS285.85±1.365.63±1.340.001*5.8±1.355.68±1.32NS DeltaDAS28 6m1.94±1.51.65±1.340.0051.93±1.511.40±1.47<0.0001 EULAR Good/Moderate/No 6m21.5/62/16.5%17.4/63.4/19.2%0.0623.9/58.7/17.4%14.9/62.9/22.2%0.009 Remission 6m13.8%11.3%NS13.5%10.9%NS DPDNp-valueRF and/or ACPA (+)DNp-value Baseline DAS285.81±1.365.65±1.36NS5.84±1.355.65±1.36NS DeltaDAS28 6m1.95±1.541.41±1.510.0071.93±1.491.41±1.510.005 EULAR Good/Moderate/No 6m24.7/58.4/16.9%13.8/65/21.2%0.0621.4/61.9/16.7%13.8/65/21.2%0.038 Remission 6m13.9%12.5%NS13.7%12.5%NS *Corrected for baseline DAS28. Conclusions In this large observational cohort of RA patients treated with RTX, seropositive patients achieved significantly greater reductions in DAS28 at 6 months compared to seronegative patients. Baseline ACPA positivity may be a better predictor for good response to RTX than RF positivity. Disclosure of Interest None Declared