The efficacy of low dose short-term prednisone therapy for remission induction in newly diagnosed rheumatoid arthritis patients

Background The ACR/EULAR recommendations endorse the use of glucocorticoids (GCs) for rheumatoid arthritis (RA) patients’ flares and as a bridge to a DMARD. However, the recommendation of low dose short-term monotherapy with (GCs) remains open to the discretion of the clinician. The aim of this study was to assess whether a short-term use of low dose prednisone monotherapy was effective in inducing remission in newly diagnosed RA patients. Methods A retrospective analysis of patients newly diagnosed with RA at a Community Health Center in North Dakota was performed based on the ACR/EULAR RA classification criteria. Demographic and clinical data were abstracted from patients’ medical charts. Patients treated with (< 10 mg/day) of prednisone up to 6 months were included. Response to prednisone was analyzed according to pre- and post-treatment DAS28-ESR score and EULAR response criteria. Results Data on 201 patients were analyzed. The mean prednisone dose was 8 mg/day (range: 5–10; SD = 1.2) and the mean treatment duration was 42.2 days (12–177; 16.9). Disease severity significantly improved from baseline to follow-up for: tender joint count (8.6 ± 4.8 vs. 1.5 ± 3.3; P < 0.001), swollen joint count (6.2 ± 5.0 vs. 1.4 ± 3.0; P < 0.001), and visual analog pain score (4.8 ± 2.6 vs. 2.1 ± 2.5; P < 0.001). DAS28-ESR disease severity significantly improved from baseline to follow-up: (5.1 ± 1.2 vs. 2.7 ± 1.3; P < 0.001). Per EULAR response criteria, 69.7% of patients showed good response to treatment and 20.4% showed moderate response. 54.2% of patients reached remission. Conclusion Short-term use of low dose prednisone monotherapy induced disease remission and improved clinical severity of RA in the majority of newly diagnosed patients.

POS0639 LONG-TERM EFFECTIVENESS OF THE RITUXIMAB HALF DOSE REGIMEN FOLLOWING A RESPONSE TO THE LICENSED DOSE IN RHEUMATOID ARTHRITIS

Background:Following initial treatment with rituximab (RTX) full dose (2x1000mg), B-cell numbers are often lower than baseline. The half dose regime (2x500mg) has been reported to be similarly effective [1]; however, there is limited long-term data on the effectiveness of switching to RTX half-dose from the real-world perspective.Objectives:To compare the 3-year RTX regime retention between patients receiving retreatment with half-dose and full-dose of RTX, and assess factors associated with maintenance of 2x500mg, with a view to establish an optimal long-term retreatment strategy in RA.Methods:An observational study was conducted on 755 consecutive RTX-treated RA patients in a single centre for over 20 years. Of these, 165/755 (22%) received at least one cycle of 2x500mg. Long-term effectiveness was assessed using RTX retention rate. Drug survival of patients treated with 2x500mg was compared with 200 RA patients receiving 2x1000mg throughout the study, matched to the number of cycle when the 2x500mg regime was initiated.Results:Of the 165 patients who received 2x500mg, 81.8% were female; mean age was 63.4 (26-91) years; mean disease duration 15.5 (2-53) years; 57 (34.5%) were bDMARDs-naïve; 121 (74%) were on concomitant DMARDs and mean DAS-28 was 3.9 (SD 1.29) at the half dose initiation. At 3 years, the retention rate was 38% for patients recieving 2x500mg compared to 87% for those on 2x1000mg; HR for half dose discontinuation was 6.17 [95%CI (3.91-12.27); p<0.001] (Figure 1A).The main reasons for 2x500mg discontinuation were poor EULAR response (30%); moderate EULAR response (30%); shorter duration of response compared to the full dose (22%); and incomplete B-cell depletion (17%). The majority of these patients (87.9%) were switched back to 2x1000mg, 5.1% received other bDMARDs and 7.1% did not receive further DMARDs.In multivariable analysis, previous TNFi use was associated with 3-year maintenance of the 2x500mg dose [OR 2.63 (1.12-6.10); p=0.024]; while higher plasmablasts at 2x500mg initiation was associated with shorter maintenance of this regime [OR 0.78 (0.67-0.97); p=0.028].There were no significant differences in 5-year RTX retention rates between patients receiving 2x500mg and switched back to 2x1000mg vs those receiving 2x1000mg throughout the study (Log-Rank=0.186) (Figure 1B).Conclusion:The use of RTX half-dose regimen was associated with poor retention at 3 years. Nevertheless, where loss of effectiveness occurs post-2x500mg initiation, switching back to 2x1000mg appears to be a pragmatic option. Patients with previous TNFi exposure and lower plasmablasts may be most suited to be commenced on the 2x500mg dose for long-term disease control.References:[1]Mariette X, et al. ARD 2014Acknowledgements:Leeds CaresDisclosure of Interests:Leticia Garcia-Montoya: None declared, Md Yuzaiful Md Yusof: None declared, Gisela Eugénio: None declared, Jean Baptiste Candelier: None declared, Sudipto Das Speakers bureau: Dr Das has received honoraria from Roche, Edward Vital Speakers bureau: Dr Vital has received honoraria from Roche, Consultant of: Dr Vital has received honoraria a from Roche, Grant/research support from: Dr Vital has received research grant support from Roche, Paul Emery Speakers bureau: Professor Emery has received honoraria from Roche, Consultant of: Professor Emery has received consultant fees from Roche, Grant/research support from: Professor Emery has received research grants paid to his employer from Roche.

AB0223 MODIFIED DOSE RITUXIMAB BIOSIMILAR IN RHEUMATOID ARTHRITIS COMPARING B-CELL DEPLETION EFFECT AND DISEASE ACTIVITY SCORES

Background:In emerging economies self-funding patients opt for less costly options, influencing both compliance and maintenance of treatment for chronic illness. Studies comparing originator rituximab 1000mgx2 and 500mgx2 doses in Rheumatoid arthritis (RA) have yielded interesting results1. Evidence of B cell depletion, measured by CD19 count, maybe a marker for disease improvement2. However effect of different dose of biosimilar Rituximab (bRTX) on B cell depletion and disease activity needs exploration.Objectives:To determine correlation of CD19 count defining B cell depletion and disease activity with different dosages of bRTX treatment.Methods:Between April 2019 and March 2020, all RA patients with DMARD failure were screened for eligibility of biologics as routine clinical practice. Depending on individual choice, after full consent, patients received either 1000mgx2 or 500mgx2 bRTX. All patients had CD19 count before and 12 months after the first dose. Effectiveness of bRTX 1000 mg×2 and 500 mg×2 was assessed by DAS28 and EULAR response. Comparative adjusted analysis was performed by analysis of variance (ANOVA).Results:Out of 468 eligible patient, 84 opted for biologic. Of which 27 patients consented for bRTX (17 female, mean age 39.5 years).13 patients opted for 1000mg×2 and 14 for 500mg×2 dose. 74% (20/27) patients were on concomitant methotrexate and 26% on hydroxychloroquine (7/27). Both doses led to significant reduction in ESR, CRP, and DAS28-ESR at 12 months (p<0.001) (Table 1).Table 1.RA outcome-measurement scores at 12 months post biosimilar Rituximab therapy.VariableBaseline12 monthsRTX 1000mg x 2(n=13)RTX 500mg x 2(n=14)RTX 1000mg x 2(n=13)RTX 500mg x 2(n=14)ESR*53.9±23.957.1±24.723.9±2.924.1±4.7CRP*6.1±3.96.9±2.92.1±0.92.3±0.9DAS28-ESR*6.1±0.36.1±0.24.0±0.44.1±0.2CD 19+ Count*# (105/L)1191.6±308.41155±289.6128.8±90.4139±90.6* p<0.0001 as compared to 12 mos vs baseline; # p<0.0001 as compared amongst groupAt the end of 12 months, compared to 1000mg, CD19 count was higher in 500mg group (p=0.25). Percentage of patients achieving EULAR moderate or no response was higher in 500mg group (37%vs29%, p=0.205), both complete and incomplete B cell depletion, but patients achieving good response was same in both groups (14.8%vs18.5%, p = 0.25). (Figure 1).Figure 1.EULAR Response at 12 monthsConclusion:Low dose bRTX is effective in DMARD refractory RA patients with similar improvements as regular dose, although CD19 depletion was less in low dose group. A larger study to establish radiographic regression with CD19 depletion and disease activity score can help in further strengthening the use of lower dose bRTX in RA leading to significant economic advantage.References:[1]Chatzidionysiou K, Lie E, Nasonov E, Lukina G,et al. Rheumatic Diseases Portuguese Register. Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration. Arthritis Res Ther. 2016 Feb 16;18:50.[2]Vital EM, Rawstron AC, Dass S, Henshaw K, Madden J, Emery P, McGonagle D. Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion. Arthritis Rheum. 2011 Mar;63(3):603-8.Disclosure of Interests:None declared

AB0108 USING RNA SEQUENCING TO IDENTIFY GENE EXPRESSION SIGNATURES ASSOCIATED WITH RESPONSE TO ABATACEPT IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) is a common chronic autoimmune disease. Abatacept (CTLA4-immunoglobulin) is one of the biological disease-modifying antirheumatic drug (bDMARD) for RA patients with indequate response to methotrexate. Recently, Yokoyama-Kokuryo et al. compared gene expression levels between abatacept responders and non-responders in RA patients using a microarray and found that type I IFN score and expression levels of nine genes may be used as a biomarker to predict response to abatacept. However, little study used RNA sequencing (RNA-seq) to identify whole blood gene expression signatures to predict therapeutic response to abatacept.Objectives:The aim of this study is to identify gene expression signatures to predict therapeutic responses to abatacept in RA patients using RNA-seq.Methods:This study is a single-center, prospective study. We used a PAX gene Blood RNA kit to collect whole blood at baseline and 4 weeks after abatacept treatment from RA patients. We also measured DAS28, physician global assessment, HAQ, ESR, CRP at baseline and 12 week to calculate EULAR response at 12 week. Patients with good EULAR response were defined as responders and those with moderate or no EULAR response were defined as non-responders.Results:We finally conducted RNA-seq for whole blood from 7 RA patients initiating abatacept therapy. Of the 7 RA patients, one was non-responder and 6 were responders. We first use DESeq2 to analyze the differentially expressed genes of non-responder and responder before taking the drug. We used hierarchical clustering and PCA to evaluate the overall similarity of the samples, and group the patient data, and find that the nonresponder can be distinguished from responders. Subsequently, we analyzed the differentially expressed genes of the two groups of non-responder and responder patients before taking the drug. Before treatment, we found that 72 genes had a higher expression in the non-responder, and 23 genes had a higher expression level in responders. Figure 1 showed the top 20 DEG Heatmap between the non-responder and responders.Using these two sets of genes for GO analysis, we found that most of the pathways in the non-responder are related to immune response and cytokine production, and most of the pathways in the responders are related to antigen processing and MHC class II.Figure 1.Top 20 DEG Heatmap between non-responder and respondersConclusion:The study showed that most of the pathways in RA patients with no EULAR response to abatacept are related to immune response and cytokine production; while most of the pathways in RA patients with moderate/good response to abatacept are related to antigen processing and MHC class II.References:[1]Yokoyama-Kokuyo W, Yamazaki H, Takeuchi T, et al. Identification of molecules associated with response to abatacept in patients with rheumatoid arthritis. Arthritis Research & Therapy. 2020;22:46.Disclosure of Interests:Hsin-Hua Chen Grant/research support from: This is an investigator-sponsored trial with Bristol-Myers Squibb who provides funding support., Wen-Cheng Chao: None declared, Jing-Rong Wang: None declared, Tai-Ming Ko: None declared

AB0270 EFFECTIVENESS OF A SWITCH FROM TOFACITINIB TO BARICITINIB IN RHEUMATOID ARTHRITIS: A RETROSPECTIVE ANALYSIS OF REAL-WORLD DATA IN SWITZERLAND

Background:Janus Kinase Inhibitors (JAKi) have recently been approved for the treatment of rheumatoid arthritis (RA) over the last years. JAKi differ in their specificity for the different JAK family members (JAK1, JAK2, JAK3 and TYK2). All three JAKis that are currently approved in Switzerland seem to have comparable efficacy on different disease stages of RA. Whether a JAKi can be effective after discontinuation of another JAKi is one of the open questions of interest according to the EULAR RA guidelines [1].Objectives:To study the effectiveness of baricitinib in patients with RA after discontinuation of tofacitinib.Methods:Longitudinal, retrospective chart review conducted between October 2019 and December 2020 of patients with RA at two Swiss centers (Kantonsspital Aarau and Inselspital Bern). Disease activity was assessed by DAS 28.Results:12 patients (1 male, 11 female) were treated with 4mg baricitinib/d after tofacitinib was discontinued. Mean age of the patients was 61 years, disease duration 140 months. Patients were previously treated with at least two conventional synthetic DMARDs and 75% with at least one biological DMARD. 58% of patients were positive for ACPA, 42% for rheumatoid factor. 50% of the patients suffered from erosive disease. Tofacitinib was stopped in 92% of the patients because of an insufficient response after a mean of 25.8 months. Moderate EULAR response was achieved in 83.3% of the patients after an average of 8 months treatment with baricitinib, and good EULAR response in 58.3% after an average of 10 months. There were no serious adverse events, neoplasms, opportunistic or serious infections during follow-up.Conclusion:The first retrospective analysis of real-world data of baricitinib following tofacitinib shows that there is a good clinical response in 70% of cases. Although limited by the number of patients this study therefore supports the notion that baricitinib after discontinuation of tofacitinib in RA patients may be an effective therapeutic option.References:[1]Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Annals of the Rheumatic Diseases. 2020;79(6):685-699. doi:10.1136/annrheumdis-2019-216655, p. 695Disclosure of Interests:Simon Kellerhals: None declared, Jennifer Amsler: None declared, Hendrik Schulze-Koops: None declared, Thomas Hügle Consultant of: GSK, Abbvie, Pfizer, Jansen, Novartis, Eli Lilly., Michael J. Nissen Consultant of: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis and Pfizer., Hasler paul Consultant of: Abbvie, Lilly, Diego Kyburz Consultant of: Abbvie, Gilead, Lilly, Novartis and Pfizer, outside of the submitted work, Rudiger Muller Consultant of: Abbvie, Novartis, Grant/research support from: Bebro Pharma

AB0231 OUTCOMES IN RHEUMATOID ARTHRITIS PATIENTS UNDER TOCILIZUMAB AS FIRST bDMARD: A REAL-LIFE MONOCENTRIC COHORT STUDY

Background:Rheumatoid arthritis (RA) is one of the most frequent systemic inflammatory rheumatic diseases, being constantly assessed regarding new disease activity monitoring tools and new therapeutic targets and therapies. Tocilizumab (TCZ) is one of the latest biological disease-modifying antirheumatic drugs (bDMARDs) approved for RA’s treatment, usually as a second line agent in daily clinical practice.Objectives:Evaluate the different disease and patient reported outcomes in patients undergoing treatment with tocilizumab as the first biologic therapy.Methods:All patients with a definite RA diagnosis who had undergone treatment with TCZ as the first biologic therapy at a tertiary hospital’s rheumatology department were included in this analysis. Diverse socio-demographic data, as well as disease and patient related outcomes were assessed at baseline, 6 and 12 months of treatment with TCZ, and posteriorly extracted from the Portuguese register of rheumatic diseases (Reuma.PT). Statistical analysis included non-parametric tests such as Wilcoxon test and univariate analysis using linear and logistic regression models.Results:Fifty-one patients were included, 88.2% females, with a median age at introduction of TCZ of 53.5 +/- 10.4 years; mainly seropositive for either rheumatoid factor (66%) or anti citrullinated peptide antibody (ACPA; 68%), with an erosive disease (75.6%) and concomitantly treated with a conventional synthetic disease modifying anti-rheumatic drug (csDMARD) (70.5%). During follow-up there was a statistically significant reduction at 6 and 12 months of TCZ treatment regarding DAS28 (4 variables) (4v) and DAS28(4V)-CRP scores (p < 0.001), SDAI (p < 0.001), CDAI (p < 0.001), 68/66 tender and swollen joint counts (TJC/SJC) (p < 0.001), ESR and CRP (p < 0.001), patient and physician VAS (p < 0.001) and HAQ score (p = 0.01 at 6 months and p < 0.001 at 12 months). Rheumatoid factor and ACPA serum levels weren’t statistically different at 6 and 12 months of treatment with TCZ compared to the initial assessment, as well as the ACR responders at the same 6 months versus those at 12 months. A majority of patients showed good EULAR response at 6 (52.6%) and 12 (56.3%) months, as well as moderate to high mean improvement in ACR core set measures at 6 (53.3±22.7) and 12 (54.3±25.2) months. Assessment of subsequent therapeutic maintenance showed that 75% of patients remained under tocilizumab with an average treatment duration of 48.8±37.7 months. Reasons for switch ranged from adverse effects (63.6%) to primary failure (18.2%) and secondary failure (18.2%). There was a significant reduction in DAS28(4V), DAS28(4V)-CRP, CDAI, SDAI, TJC and SJC, ESR, CRP, patient and physician VAS and HAQ scores between 6 and 12 months of therapy (p < 0,001). ACR and EULAR responses didn’t differ significantly between assessments at 6 and 12 months. In the absence of a representative number of RA patients on TCZ monotherapy, it wasn’t possible to draw conclusions about the need to use combined therapy with a csDMARD for better clinically significant response.A higher degree of ACR response at 6 months was associated with higher serum rheumatoid factor levels (OR 1.13, p < 0.05) at baseline, while a lower degree of response was seen with higher TJC (p = 0.05) and HAQ score (p < 0.01). ACR response at 12 months was lower in patients with erosive disease at baseline (p < 0.05). Regarding EULAR response criteria at 6 months, there was a negative association with higher TJC (p < 0.05), while at 12 months the negative trend was associated with ESR levels (p < 0.05) and HAQ scores (p < 0.05) at baseline.Conclusion:There seems to be evidence of good therapeutic response to TCZ in bDMARD naïve RA patients assessed at 6 months from baseline, without evidence of significant improvement of response measures further down the line. Basal serum rheumatoid factor levels, TJC, HAQ scores and the presence of erosive disease may have some predictive value on the therapeutic response. Further studies comparing TCZ as the first bDMARD in naïve RA patients against TNF inhibitors are needed.Disclosure of Interests:None declared

POS0488 THE IMPACT OF ANTINUCLEAR ANTIBODIES INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA AGENTS ON THE LONG-TERM TREATMENT OUTCOMES IN RHEUMATOID ARTHRITIS PATIENTS

Background:The seroconversion of antinuclear antibodies (ANA) induced by anti-tumour necrosis factor alpha (anti-TNF-α) therapy remains a matter of concern in various inflammatory conditions namely rheumatoid arthritis. However, evidence is still scarce regarding the impact of these autoantibodies on the clinical response to treatment in these patients.Objectives:This study aimed to explore the impact of ANA induced by anti-TNF-α therapy on the outcomes of treatment in patients with rheumatoid arthritis over two years of follow-up.Methods:An observational retrospective cohort study was conducted with two years of follow-up. Patients diagnosed with rheumatoid arthritis, according to the American College of Rheumatology (ACR) criteria, and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα agent as first biologic between 2003 and 2018 were included. Patients with positive ANA (titer ≥100) and/or positive anti-double stranded DNA (anti-dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. Disease Activity Score for 28 joints (DAS28), DAS28 delta, Health Assessment Questionnaire (HAQ), HAQ delta were assessed at baseline, 6, 12, 18 and 24 months. Clinical response was evaluated by EULAR criteria and three response categories were defined: good, mild and no response. The rate of switch of biological treatment was assessed over 24 months. To examine the differences between groups with and without ANA seroconversion independent samples t test for normally distributed continuous data, Mann-Whitney U-tests for non-normally distributed continuous data and Chi-square tests for categorical data were used. Logistic regression models were used to assess the effects of ANA seroconversion on clinical response to treatment over 6, 12, 18 and 24 months.Results:A total of 185 patients (mean age of 49.3±10.9 years old; 85.4% female) with a median follow-up of 7 [4-14] years were included. We found an ANA seroconversion rate (titer ≥100) of 77.3% (n=143) with median time of 36 [15-72.3] months. There were no differences among groups regarding age, gender, disease duration, be seropositivity or not (for rheumatoid factor and/or anti-citrullinated protein antibodies) and have an erosive disease or not. DAS28 delta was significantly different (p=0.035) between group with positive ANA (2.01±1.29) and negative ANA (1.15±1.51) at 6 months. DAS28 was significantly different (p=0.014) between group with positive ANA (5.06±3.39) and negative ANA (3.99±1.43) at 12 months. No statistically significant differences were found in the DAS28, DAS28 delta, HAQ, HAQ delta at 18 and 24 months and in the EULAR response at any time. Switch rate was significantly different between patients with ANA seroconversion (median 1[0-1]) versus absence of seroconversion (median 0[0-1]), p=0.025. In the regression model ANA seroconversion did not predict switch rate and EULAR response over time.Conclusion:This study showed that the majority of patients with rheumatoid arthritis treated with an anti-TNF-α agent developed ANA and that their presence may be associated with worse clinical results (DAS28) at 6 and 12 months. In fact, previous research suggested that a decrease in anti-TNF-α drug concentration due to the production of autoantibodies may lead to worse outcomes of treatment. Moreover, our data demonstrated that patients with ANA seroconversion had a higher switch rate. Despite these results, there are no differences in the EULAR response between the two groups and ANA seroconversion did not predict this response over time. Therefore, ANA induced by anti-TNF-α agents should be monitored in patients with rheumatoid arthritis and its impact on treatment must be considered. Further research is needed to explore these results through large-scale prospective studies.Disclosure of Interests:None declared

The association between increased body mass index and response to conventional synthetic DMARD treatment in rheumatoid arthritis: Results from the METEOR database

Background Few data exist on the association between increased BMI and response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). We aimed to explore the association between increased (overweight or obese) BMI on csDMARD-prescribing, methotrexate-dose and disease activity over 12-months. Methods Participants in an international RA database were stratified into early (&lt;1year post-diagnosis) and established RA. EULAR response, DAS28 remission and treatments were recorded at baseline, 6-months and 12-months. Increased BMI was explored in early and established RA, as predictors of good EULAR response, DAS28 remission, number of csDMARDs and methotrexate-dose, using logistic and linear regression. Results Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs, compared with normal BMI. In patients taking methotrexate, overweight and obese patients with early and established RA were exposed to higher methotrexate doses (mono- and combination-therapy), with a mean dose of 20mg/week, compared to 15mg/week in those of normal BMI. Conclusion We observed, compared to patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimisation of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated.

Prediction of response of methotrexate in patients with rheumatoid arthritis using serum lipidomics

Methotrexate (MTX) is a common first-line treatment for new-onset rheumatoid arthritis (RA). However, MTX is ineffective for 30–40% of patients and there is no way to know which patients might benefit. Here, we built statistical models based on serum lipid levels measured at two time-points (pre-treatment and following 4 weeks on-drug) to investigate if MTX response (by 6 months) could be predicted. Patients about to commence MTX treatment for the first time were selected from the Rheumatoid Arthritis Medication Study (RAMS). Patients were categorised as good or non-responders following 6 months on-drug using EULAR response criteria. Serum lipids were measured using ultra‐performance liquid chromatography–mass spectrometry and supervised machine learning methods (including regularized regression, support vector machine and random forest) were used to predict EULAR response. Models including lipid levels were compared to models including clinical covariates alone. The best performing classifier including lipid levels (assessed at 4 weeks) was constructed using regularized regression (ROC AUC 0.61 ± 0.02). However, the clinical covariate based model outperformed the classifier including lipid levels when either pre- or on-treatment time-points were investigated (ROC AUC 0.68 ± 0.02). Pre- or early-treatment serum lipid profiles are unlikely to inform classification of MTX response by 6 months with performance adequate for use in RA clinical management.

Low-dose rituximab protocol in rheumatoid arthritis—outcome and economic impact

Objectives A significant proportion of RA patients, particularly those associated with poor prognostic factors, fail on conventional DMARDs (cDMARDs). Although rituximab (RTX) has been effective in these patients, the cost of therapy makes it unaffordable, particularly in poor and developing countries. Numerous, albeit small, studies using lower doses have shown contradictory results. We aimed to analyse the effectiveness of a low-dose RTX protocol based on clinical outcomes in RA patients. Methods Seropositive RA patients with moderate to high disease activity (DAS28-ESR &gt; 3.2) despite combination cDMARDs, treated with RTX, were included in retrospective analysis. All patients were treated according to a predefined protocol, using 500 mg RTX with ongoing cDMARDs at baseline and repeat dosing at 6 weeks or beyond, on lack of moderate to good EULAR response. The B cell count was assessed at baseline, 2 and 24 weeks. Results At 12 weeks, 93% of 166 patients [mean (s.d.) age, 51.5 (11.96) years, 25 men and 141 women, with a disease duration of 10.4 (6.29) years] achieved moderate to good EULAR response. At 24 weeks, 90.8% of patients achieved moderate to good EULAR response, 19.8% achieved low disease activity and 29.5% achieved remission, with a mean change in DAS28-ESR from baseline of 2.9 (1.3). RTX failure and relapse were seen in 5.4% and 3.6%, respectively. The response was maintained for 12.3 (7.2) months with a mean RTX dose 521.1 (100.8) mg. Adverse events were seen in 9.6%. When compared with the standard dosing regimen with the originator molecule, a cost reduction of 90% was achieved. Conclusion A low-dose RTX regimen achieved reasonably good clinical outcomes at the end of 6 months, with a significantly lower cost.