AIM To determine in a noninferiority study whether mesalamine foam is as effective as mesalamine liquid enema for inducing clinical remission in patients with active left-sided ulcerative colitis (UC). METHODS In a multicenter investigator-blind trial, 375 patients with mild-to-moderate UC were randomized to receive mesalamine foam 1 g/80 mL/day or mesalamine liquid enema 1 g/100 mL/day for 4 wk (W). Inclusion criteria were: disease extension at least 5 cm from anorectal junction and not above splenic flexure and Clinical Activity Index (CAI) 1–4 ≥ 4. Primary end point was clinical remission at W4 defined as a CAI 1–4 ≤ 2. Noninferiority of the foam to liquid enema was declared if the lower limit of the 97.5% unilateral confidence interval (97.5% CI) of the difference in remission rates between foam and liquid enema groups was greater than −15%. RESULTS Remission rates at W4 in foam versus liquid were 68.3%versus 73.6% in per protocol (PP) population (lower limit of 97.5% CI −15.1%) and 66.7%versus 70.5% in intention-to-treat (ITT) population (97.5% CI −13.4%). Remission rates at W2 were 48.1 %versus 50.6% in ITT (97.5% CI −12.8%) and 49.1%versus 52.1% in PP (97.5% CI −13.8%) in foam versus liquid, respectively. Both treatments were well tolerated. CONCLUSIONS A 4-wk treatment of 1 g mesalamine foam induced a clinical remission in 68% patients versus 73% with 1 g mesalamine liquid enema. Although the noninferiority of mesalamine foam could not be strictly demonstrated at W4 in the PP analysis, it was achieved in the ITT population and at W2 in both populations. Mesalamine foam represents a therapeutic alternative to mesalamine liquid enema in patients with mild-to-moderate active proctitis and proctosigmoiditis.
P746 Aims: Compare efficacy and tolerance of a CNI-free regimen and a classical immunosuppressant regimen with CsA, both regimens including an induction (rATG), MMF and steroids. Methods: 150 patients have been prospectively randomized to receive SRL (15mgx2 then 10mg/d, targeted C0:10-15ng/ml) or CsA (6-8mg/kg/d, targeted C0:75-250ng/ml). Primary endpoint was glomerular filtration rate (GFR) (Nankivell) at 12 months. Results: 100 patients (49 SRL, 51 CsA) were evaluated at month 3. Demographic data were comparable. Mean SRL and CsA doses and C0 were 7.6mg/d and 16ng/ml, 306mg/d and 168ng/ml, respectively. Mean MMF dose was 1.7g and 1.8g/d in SRL and CsA, respectively. Patient and graft survivals, biopsy proven acute rejection were similar (100, 92, 13 vs 97, 95,16% for SRL vs CsA, respectively). Study withdrawal (20 vs 11%), study withdrawal due to adverse event (12 vs 9%), delayed graft function (6 vs 0%), slow graft function (27 vs 29%), were not significantly different in SRL vs CsA. GFR was similar in ITT (61 vs 58ml/min) but was significantly higher in observed data analysis (70 vs 60ml/min, p=0.004) in SRL vs CsA. Serum creatinine values were similar in SRL vs CsA in ITT and in observed data analysis (125 vs 139μmol/l). 24-hour proteinuria (1 vs 0.5g) was not significantly different in SRL vs CsA. Delayed cicatrisation (15 vs 8%) was not significantly different in SRL vs CsA. Lymphoceles were more frequent in SRL (22 vs 2%, p=0.005). Rate of infection were as follow:all (54 vs 53%); CMV (7 vs 22%, p=0.07); systemic (14 vs 8%); others (48 vs 38%) in SRL vs CsA, respectively. Anemia, leucopenia and thrombopenia and blood pressures were comparable. Cholesterol and triglycerides were higher in SRL (6.5 vs 5.5mmol/l and 3.6 vs 1.9mmol/l, p=0.01). Conclusions: At 3 months, a SRL based regimen provides comparable patient and graft survivals, acute rejection rates, more hyperlipidemias and lymphoceles, higher GFR in observed data analysis and a tendency to less CMV infections. 6 month data of 150 patients will be presented.
Few data are available on the epidemiology and management of GCA in real life. We aimed to address this situation by using health insurance claims data for France.This retrospective study used the Echantillon Généraliste de Bénéficiaires (EGB) database, a 1% representative sample of the French national health insurance system. The EGB contains anonymous data on long-term disease status, hospitalizations and reimbursement claims for 752 717 people. Data were collected between 2007 and 2015. The index date was defined as the date of the first occurrence of a GCA code. Demographics, comorbidities, diagnostic tests and therapies were analysed. Annual incidence rates were calculated, and incident and overall GCA cases were studied.We identified 241 patients with GCA. The annual incidence was 7-10/100 000 people ⩾50 years old. Among the 117 patients with incident GCA, 74.4% were females, with mean age 77.6 years and mean follow-up 2.2 years. After the index date, 51.3% underwent temporal artery biopsy and 29.1% high-resolution Doppler ultrasonography. Among the whole cohort, 84.3% used only glucocorticoids. The most-prescribed glucocorticoid-sparing agent was methotrexate (12.0%).The incidence of GCA in France is 7-10/100 000 people ⩾ 50 years old. Adjunct agents, mainly methotrexate, are given to only a few patients. The use of temporal artery biopsy in only half of the patients might reflect a shift toward the use of imaging techniques to diagnose GCA.
Although the use of a biologic as monotherapy is not the standard in Rheumatoid Arthritis (RA), it concerns around a third of the patients. The objectives of the Act Solo study was to evaluate tocilizumab (TCZ) alone (Mono) or in combination (Combo) at 12 months in real life.
Methods
Prospective, multicenter, longitudinal, non-interventional 12-month study in RA pts requiring TCZ according to their physician. Besides drug retention rate, efficacy and safety, the effect of Mono when compared to Combo was evaluated using a propensity score. Efficacy population was pts fulfilling inclusion and non-inclusion criteria and with ≥1 TCZ infusion. Safety population was all pts with ≥1 TCZ infusion.
Results
608 pts were recruited of whom 603 were analysed for safety and 577 (Total) for other endpoints. At baseline: mean age 57±13 years, 454 (79%) females, at least 1 co-morbidity: 409 (71%), mean RA duration 11±9 years, RF or ACPA positive: 478 (86%), erosive disease: 435 (77%), mean DAS28 5.2±1.3. Past RA treatments included DMARDs + biologics in 75%, only DMARDs in 24%. MTX was previously prescribed in 95% of pts and in 71% within the last 2 years. TCZ Mono was initiated in 228 (40%) pts and TCZ Combo in 349 (60%) pts of whom 80% received MTX (mean 16±5mg/w). Steroids (GCs) were used in 386 (67%) pts (mean 10±7mg/d). 337 pts completed M12 visit. 194 pts withdrew for: AE 53 pts, inefficacy 88, patients wish 12, lost to follow-up 23, other 18. At M12, drug retention rate was 69% in Total, 67% in Mono, 71% in Combo (Fig.). Mean number of TCZ infusions was 9.4±4.1; mean time between infusions was 31.8 ±12.6 days. 29% of the pts experienced at least 1 discontinuation, 25% and 33% in Mono and Combo groups respectively. DMARD was added in 20 Mono and definitely stopped in 25 Combo pts. 170 (50%) pts remained on GCs, 66 (51%) in Mono group and 104 (50%) in Combo group. At M12, mean DAS28 in Total, Mono and Combo were 2.4±1.3, 2.4±1.3 and 2.3±1.2 respectively. DAS28 remission was 35% in Total, 35% and 36% in Mono and Combo respectively (p=0.83). Using the propensity score, no effect of Mono was observed on drug retention HR=1.194 [0.852,1.673], p=0.30; DAS remission OR=1.111 [0.773,1.597], p=0.57; or GCs use OR=0.880 [0.558,1.387], p=0.58 at M12. No new safety signal was reported. 325 (54%) patients had at least one AE, 74 (12%) had at least one serious AE with no differences between Mono and Combo.
Conclusions
The Act Solo study confirms, in real life, the clinical results of RCTs showing a comparable efficacy of TCZ as monotherapy when compared to combotherapy. No new safety signal occurred.
Disclosure of Interest
J. Tebib: None declared, I. Idier Employee of: Chugai Pharma France, M. Coudert: None declared, J.-F. Maillefert: None declared, R.-M. Flipo Consultant for: Roche SAS and Chugai Pharma France
A randomized, 2‐way, crossover study was conducted in 30 volunteers to compare the pharmacokinetic profile of a new once‐daily dosing regimen of mesalazine (1 × 4 g/d) with the current twice‐daily dosage (2 × 2 g/d) used in many European countries. The 2 dosages were administrated orally for 8 days, separated by a 2‐week washout. Plasma concentrations of mesalazine and N‐acetyl‐mesalazine were determined on days 1 and 8 by a validated high‐performance liquid chromatography method and C max , t max , and AUCs calculated. The bioequivalence was obtained for a 90% confidence interval of the AUC 0–24h ratio (test/reference) for mesalazine and N‐acetyl‐mesalazine on days 1 and 8, within the range of 0.80 to 1.25. The bioequivalence was demonstrated on day 1 for mesalazine and N‐acetyl‐mesalazine and on day 8 for mesalazine. As it is desirable to offer patients a preparation with a less frequent administration to enhance compliance, this once‐daily regimen may be an attractive dosing option.
Introduction Using a biologic disease-modifying antirheumatic drug (bDMARD) as monotherapy in clinical practice for patients with rheumatoid arthritis (RA) is common and recognised by health authorities although current guidelines recommend to combine them with conventional synthetic (cs)DMARDs. This study mainly aimed to search for real-life factors influencing the use of tocilizumab as MONO or in combination (COMBO). Methods In this non-interventional, prospective, national, multicentre study, data were collected every 3 months over a 12-month period in RA patients starting tocilizumab. The proportion of monotherapy patients was described, together with significant explicative factors. Results Among the 577 analysed patients recruited from January 2012 to August 2013 (228 monotherapy patients; 40%), 79% were women, mean RA duration was 11±9 years, previous RA treatments included bDMARDs and csDMARDs in 75% of cases and mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 5.2±1.3 at inclusion. Explicative factors for monotherapy were at least 65 years (OR=1.47, p=0.0485), no methotrexate within the two last years (OR=5.96, p<0.0001), past severe infection (OR=1.99, p=0.0272) and higher baseline DAS28-ESR (OR=1.22, p=0.0086). Regarding clinical results (DAS28-ESR, Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) low disease activity and remission; ACR20/50/70 and European League Against Rheumatism (EULAR) response; Health Assessment Questionnaire Disability Index (HAQ-DI) score), no relevant differences between monotherapy and combination patients were observed at 1 year. A total of 23 tocilizumab-treated patients (4%) experienced serious infections; no new safety signals were noted with no differences between groups. Conclusions ACT-SOLO confirms the high proportion of RA patients receiving tocilizumab as MONO in clinical practice. The study also showed that clinical results at 1 year were similar between MONO and COMBO patients in a real-life setting. Trial registration number NCT01474291 .
