Background-Systemic sclerosis (SSc, scleroderma) in either its diVuse or limited skin forms has a high mortality when vital organs are aVected. No treatment has been shown to influence the outcome or significantly aVect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. Methods-Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being <70% of the predicted value in 18/36 (50%). Pulmonary hypertension was described in 7/37 (19%) patients and renal disease in 5/37 (14%). The Scl-70 antibody was positive in 18/32 (56%) and the anticentromere antibody in 10% of evaluable patients. Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor, alone or in combination. Thirty eight patients had ex vivo CD34 stem cell selection, with additional T cell depletion in seven. Seven conditioning regimens were used, but six of these used haemoimmunoablative doses of cyclophosphamide +/-anti-thymocyte globulin +/-total body irradiation. The median duration of follow up was 12 months (3-55). Results-An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. Conclusion-Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

Addition of 10 mg prednisone daily to an MTX-based treatment strategy in early rheumatoid arthritis results in a lower initiation rate of a first bDMARD and significantly better radiographic outcomes, yet does not result in more GC-related comorbidities.

Background:For rheumatoid arthritis (RA) patients included in clinical trials, background treatment with glucocorticoids (GCs) is quite common (40–60%), but their potential contribution to efficacy and safety of the disease modifying anti-rheumatic drug (DMARD) tested in that trial has rarely been evaluated.Objectives:To establish whether a stable GC dose at baseline and during the study contributed to the efficacy and safety of TCZ monotherapy initiated in RA patients in 4 TCZ RCTs. In addition, to investigate the same issue in the comparator arms of these trials, in which adalimumab (ADA) or methotrexate (MTX) was initiated.Methods:Data from 4 randomized controlled double-blind trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with TCZ monotherapy arms was analysed in this post hoc analysis [1–4]. Study participants were MTX-naïve, intolerant or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR). Because of differences between the studies in region, and baseline RA duration and disease severity, analyses were done separately for each study. Stable GC dose at baseline was allowed and was to be continued unchanged during the first 24 weeks. Analyses of covariance (ANCOVA) of change from baseline to Week 24 in CDAI and DAS28 and logistic regression analyses at Week 24 for CDAI remission and ACR50 were performed. Repeated measures analyses using all visits up to week 24 were also done. Incidence rates of serious adverse events (SAEs) were assessed by GC use.Table 1Disease Activities at week 24 of GC Users versus non-GC Users per Treatment per StudyResults:Baseline characteristics were mostly comparable between GC users and non-GC users in each treatment arm for each study. The adjusted differences (95% CIs) of CDAI change at week 24 between GC and non-GC users in TCZ arms of AMBITION, FUNCTION, ACT-RAY and ADACTA were -1.4 (-4.8, 2.1), 0.8 (-2.5, 4.1), 1.2 (-4.0, 6.3) and -4.2 (-9.7, 1.4), respectively (table 1). CDAI remission rates, ACR50 response rates and DAS28 score changes at 24 weeks neither were significantly different between GC users and non-GC users in the TCZ arms, nor in the MTX and ADA arms (table 1). Repeated measures analyses to week 24 showed no significant differences in DAS28 or CDAI. Statistically significant predictors for the various clinical outcomes included baseline CDAI, baseline DAS28, age, sex, RA duration and region. A numerically higher but not significantly different SAE rate was seen in the GC-arms of all four trials, compared to the non-GC-arms.Conclusions:No evidence was found that GC treatment at baseline and continued at a stable dose affects either clinical efficacy or safety over 24 weeks of TCZ, MTX, or ADA monotherapy initiated at baseline in RA clinical trials.References[1]Jones G, et al. Ann Rheum Dis2010;69:88–96.[2]Dougados M, et al. Ann Rheum Dis2013;72:43–50.[3]Gabay C, et al. Lancet2013;381:1541–50[4]Burmester GR, et al. Ann Rheum Dis2017;76:1279–84.Disclosure of Interest:M. Safy Grant/research support from: Research grant from AZ, J. Jacobs: None de...

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BackgroundThe U-Act-Early trial was a 2 year placebo controlled, double-blind randomised controlled trial in early (DMARD-naïve) RA patients treated to the target of sustained remission (SR), starting with tocilizumab (TCZ), methotrexate (MTX) or their combination (TCZ +MTX)1. When the treatment target was achieved, medication was tapered and stopped, if patients remained in remission. During the trial period, the strategies starting with TCZ were more effective than the strategy initiating MTX only. Subsequently, patients were followed for 3 years, during which treatment was open and according to usual care.ObjectivesTo establish the effectiveness of step-up strategies starting with MTX, TCZ or their combination in early RA over a 5 year period.Methods226 of the 317 patients starting in the U-Act-Early trial (initial strategy: 75 TCZ +MTX, 79 TCZ, 72 MTX) participated in the 3 year follow-up phase.DAS28 was collected every 3 months during the first year and every 6 months thereafter.The primary endpoint, was SR, defined as DAS28 <2.6 AND 28 joint count ≤4 for>24 weeks. Secondary endpoints were sustained drug free remission (sDFR), defined as remission for ≥3 months after tapering and stopping all medication during SR, and DAS28 over 5 years.Differences between the randomised strategies in proportions of patients achieving SR and sDFR and durations of SR and sDFR were tested with Cochran-Mantel-Haenszel and Kruskal-Wallis tests, respectively.A mixed model analysis was used to compare DAS28 over time, with a random intercept and fixed effects for: treatment, visit-week, the interaction visit-week*treatment, and it was corrected for gender, age, and for DAS28, RA-duration, CRP and RF-positivity at baseline.ResultsBaseline characteristics at the start of U-Act-Early of the patients included in this 3 year follow-up study were not significantly different from those of all patients included in U-Act-Early trial. Over 5 years, SR was achieved in 224/226 (99%) patients without significant differences (p=0.15) between the initial treatment strategies in proportions of patients achieving it, nor in durations (p=0.96) of these endpoints (table 1). Neither between-group significant differences were found for sDFR (proportion; p=0.10, duration; p=0.27), only a tendency for longer duration in TCZ +MTX. The mean DAS28 over 5 years was not significantly different between initial strategy groups (figure 1), but it was on average 0.15 (95% CI −0.12 to 0.42) units higher in the TCZ(+MTX) groups, compared to MTX initiation group.Abstract FRI0026 – Table 1Outcome for sustained (drug free) remission over 5 yearsAbstract FRI0026 – Figure 1DAS28 over time stratified for initial treatment strategyConclusionsOn the short term, initiation of TCZ-based strategies yields the most benefit, but on longer term, no difference in important clinical outcomes was found anymore between initial strategy groups, probably due to continuation of the treat-to-target principle2. Almost all patients achieved SR over 5 years, with a tendency for longer dura...