ObjectivesTo investigate the efficacy and tolerability of amtolmetin guacil (AMG; Niselat®, Dr. Reddy's Laboratories Ltd, India) versus previous therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with knee osteoarthritis (OA) and signs of dyspepsia.MethodsThe open-label observational study included 220 patients aged 30–65 years who suffered from knee OA and intense pain during NSAID intake and had symptoms of dyspepsia in the absence of contraindications to the use of AMG. Among the comorbidities that generally occurred in 68% of the patients, there was a preponderance of hypertension (42%), lower extremity varicose veins (6.4%), and diabetes mellitus (6%).Treatment efficacy was evaluated using three domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), by also taking into account pain intensity and general health assessment on the visual analogue scale. A Severity of Dyspepsia Assessment (SODA) scale was used to rate dyspepsia.ResultsAMG had a marked analgesic effect confirmed by 40% or more pain reduction thatoccurred in 72.5% of the patients. The high analgesic effect of AMG was confirmed by a statistically significant (p<0.001) reduction in the WOMAC index (pain and stiffness) and by an increase in functional activity. Therewas a significant decrease in painless and painful signs of dyspepsia, as well as positive changes in the measures“overall assessment of dyspepsia severity” (p<0.001) and “satisfaction with treatment”. Overall assessment ofAMG tolerability was only positive: excellent (33%), good (56%), and satisfactory (11%). There were no seriousadverse events (AE). AE were graded as moderate and mild in 8 and 82% of cases, respectively. AE were recordedin 7.7% of the patients.AMG had a marked analgesic effect confirmed by 40% or more pain reduction that occurred in 72.5% of the patients. The high analgesic effect of AMG was confirmed by a statistically significant (p<0.001) reduction in the WOMAC index (pain and stiffness) and by an increase in functional activity. There was a significant decrease in painless and painful signs of dyspepsia, as well as positive changes in the measures “overall assessment of dyspepsia severity” (p<0.001) and “satisfaction with treatment”. Overall assessment ofAMG tolerability was only positive: excellent (33%), good (56%), and satisfactory (11%). There were no serious adverse events (AE). AE were graded as moderate and mild in 8 and 82% of cases, respectively. AE were recorded in 7.7% of the patients.ConclusionsThe findings suggest that AMG offers good prospects for knee OA treatment.AcknowledgementsOtteva A.N., Dubikov A.I., Yakupova S.P., Ivanova O.N., Korshunov N.I., Vaisberg A.R., Abyshev R.A., Tartynov A.V.Disclosure of InterestNone declared

Background:Rituximab (RTX) is successfully used in patients with active rheumatoid arthritis (RA) who previously received biological disease-modifying antirheumatic drugs (bDMARDs) at a dose of 1000 mg. Previous preclinical and clinical studies showed that BCD-020 is highly similar to innovator RTX. ALTERRA study demonstrated that first-line use of 600 mg BCD-020 is very effective in bDMARDs naive patients with RA.Objectives:The goal of ALTERRA study was to evaluate the efficacy and safety of the alternative dosing regimen (600 mg) of BCD-020 in bDMARDs naive patients with RA.Methods:ALTERRA study was conducted as multicenter randomized double-blind placebo-controlled phase 3 study. After the screening patients were stratified by age, anti-CCP level and DAS28 score, randomized (2:1) into 2 arms and received BCD-020 (in combination with methotrexate (MTX)) in a dose 600 mg IV or placebo (in combination with MTX) on day 1 and day 15, then, if the activity of arthritis persisted after 24 wks of study, a second course was provided. Patients were observed up to 52 wks.Results:A total of 159 patients were enrolled in ALTERRA study, 107 patients in BCD-020 arm and 52 patients in placebo arm.Efficacy:ACR20 at wk 24 was reached by 65.69% of patients in BCD-020 arm and 29.41% in placebo arm (p=0.00005, the difference in proportion of registration ACR20 with 95%CI was 29.41 [19.27%; 53.28%], margin 10.5%) in per protocol population, so hypothesis of superiority was confirmed. The performed analysis showed a much more pronounced decrease in the DAS28–4 (ESR) index in BCD-020 arm compared with placebo arm (p=0.0006) at wk 24. A much more significant decrease in change of the HAQ-DI index was also shown in the BCD-020 arm (p=0.008). Analysis of efficacy at wk 52 showed the preservation of the response after 2 courses of therapy with BCD-020, 600 mg (in combination with MTX): ACR20 reached by 84.5%, ACR50 – by 54.6%, ACR70 – by 29.9 % of patients.Safety:BCD-020 showed a favorable safety profile with no significant difference with placebo use (in combination with MTX). After 24 wks patients of both groups developed high similar level of related adverse events: 16.8% of patients in BCD-020 arm and 11.76% in placebo arm (p=0.555). There were only 3 cases of severe adverse events (2.8%) in BCD-020 arm and 2 cases (3.92%) in placebo group. From wk 24 to wk 52: 13.08% of patients (who received 2 courses of BCD-020) and 19.61% of patients (who received one course of BCD-020 after 24 wk) developed related adverse events.Figure 1 ACR 20/50/70 in bDMARDs naive patients with RA after 24-wk treatment of BCD-020/placebo (in combination with MTX).Conclusions:ALTERRA study showed high efficacy and favorable safety profile of RTX biosimilar BCD-020 at a dose of 600 mg in combination with MTX in bDMARDs naive patients with RA.Disclosure of Interest:V. Mazurov: None declared, L. Denisov: None declared, I. Gordeev: None declared, O. Nesmeyanova: None declared, T. Plaksina: None declared, E. Ilivanova: None declared, D. Krechikova: None declared, E...

BackgroundInfliximab (IFX) was one of the first genetically engineered biologics successfully applied for medical use in patients with active RA and patients with AS. Previous preclinical studies showed that BCD-055 is highly similar to innovator IFX.ObjectivesThis abstract presents results from three clinical trials of infliximab biosimilar, BCD-055, including comparative data on pharmacokinetics (PK), efficacy and safety in a variety of patient populations.MethodsAll three studies were conducted as international multicenter randomized double-blind studies in direct comparison with innovator IFX. ASART-1 study (Phase 1, PK study) and ASART-2 study (Phase 3, efficacy and safety study) were conducted in patients with AS. After the screening patients were stratified by CRP and BASDAI score, randomized (1:1 ratio in ASART-1; 2:1 ratio in ASART-2) into 2 arms and received BCD-055 or innovator IFX at a dose 5 mg/kg IV on day 1 wk 0, 2, 6 and then every 8 wks (up to wk 54). LIRA study (Phase 3 study) was conducted in patients with active RA who were stratified by age and DAS28 score, randomized (2:1) into 2 arms and received BCD-055 or innovator IFX at a dose 3 mg/kg IV on day 1 wk 0, 2, 6 and then every 8 wks (up to wk 54).ResultsA total of 91 patients were enrolled in ASART-1 study, 198 patients - in ASART-2 study and 195 patients - in LIRA study in Russia and Belarus. PK characteristics were equivalent for BCD-055 and innovator IFX. After the single administration 90%CI for the ratio of geometric means for AUC0–336 was 86.40% – 110.09%, for Cmax – 82.70% – 109.83%. After multiple-dose administration 90%CI for the ratio of geometric means for AUC0-tau was 81.35% – 121.13%, for Cmax,ss – 90.16% – 117.32%. Efficacy: BCD-055 is non-inferior to innovator IFX both in RA and AS patients: ACR20 at wk 14 was reached by 75.83% of patients in BCD-055 group and 74.19% in innovator IFX group (p=0.951, 95% CI for difference in proportion [-12.90%; 16.18%], margin -20%), ASAS20 at wk 30 - by 81.30% and 67.74% respectively (p=0.061, 95% CI for difference in proportion [-1.18%; 28.28%], margin -17.5%). Safety: BCD-055 and innovator IFX showed highly similar safety profiles in all three studies without cases of unexpected toxicity. The rates of AEs were equivalent for both drugs and varied from 47% in patients with AS to 53% in patients with RA. Immunogenicity assessment didn't find any significant difference between BCD-055 and innovator IFX, anti-drug antibodies occurred at the same rate irrespectively to the group.ConclusionsBCD-055 is highly similar to innovator IFX in patients with active RA and in patients with AS in terms of efficacy, safety and PK.References EMA/CHMP/BMWP/403543/2010. Disclosure of InterestL. Denisov: None declared, I. Gordeev: None declared, V. Mazurov: None declared, A. Lila: None declared, E. Zonova: None declared, O. Nesmeyanova: None declared, E. Ilivanova: None declared, T. Plaksina: None declared, A. Eremeeva Employee of: JCS BIOCAD, A. Artemeva Employee of: JCS BIOCAD, E. Chernyaeva Employee of: JCS BI...

with cellular changes to chondrocytes, an increase in degradative stimuli and changes to the proteins of the extracellular matrix. It is not known to what extent these changes occur with age or if they are specific to diseased cartilage. Herein, we systematically investigated the changes that occur with age in mouse cartilage. Methods: C57/BL (ICRFa) mice have been selectively bred for longevity. Knee joints were collected (4 mice/group) at 3, 6, 12, 24, 30 months of age. Histology was performed with sections stained with hematoxylin & eosin (H&E), safranin O, Picro-sirius red and antibodies to cleaved type II collagen, MMP13, nitro-tyrosine (as a measure of oxidative stress), cleaved LC3B (as a measure of autophagy) and Bcl-2 /Bax (as a measure of apoptosis). Results: Our data indicate that a progressive degradation and loss of matrix occurs with age particularly in the load bearing area of cartilage. An increase in oxidative stress, MMP13 expression and type II collagen cleavage products occur with age with a concomitant decrease in autophagy and increase in apoptosis. Conclusions: This study demonstrates that many of the changes that occur in osteoarthritis are found in cartilage with increasing age. The increase in the level of oxidative stress, MMP-13 and type II collagen cleavage products explain the complete loss of cartilage tissue from load bearing regions of the joint in 30 month old mice joints. These changes explain the marked predisposition to osteoarthritis with increasing age.

BackgroundRehabilitation techniques, including physical exercises, physiotherapy, occupational therapy, patient education, give the patients with rheumatoid arthritis (RA) the strategies necessary to manage their disease in addition to drug treatment [1–4].ObjectivesTo evaluate the efficacy of 12-month complex rehabilitation program in patients with RA receiving biologic DMARDs.Methods64 patients with RA (87,5% females, age of 19 to 62 years, disease duration of 9 months to 10 years) were included and randomized into 2 groups. All patients received biologic DMARDs (adalimumab subcutaneously 40 mg once every 2 weeks or etanercept subcutaneously 50 mg per week or abatacept intravenously 750 mg once every 4 weeks) with methotrexate 20–25 mg per week. 34 study group patients underwent 12-month complex rehabilitation program: 15-min local air cryotherapy (−60°C, Criojet Air C600) for joints, 2 courses for 10 sessions with a mean interval of 6,4 months; 45-min therapeutic exercises 3 times a week, at first under the supervision of a trainer, further own at home; 45-min occupational therapy (joint protection strategies, use of assistive devices and adaptive equipment), 10 sessions; wrist and knee orthoses, orthopedic insoles; education program (4 daily 90-min studies). 30 patients received only drug therapy (control). Tender and swollen joint count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), joint pain on 100-mm VAS, DAS28, HAQ, RAPID3, hand grip strength, the average powers of knee extension and ankle flexion by EN-TreeM movement analysis were evaluated at baseline and at 12 months.Results27 patients finished 12-month rehabilitation program. 7 patients did not complete the study, because they had a low compliance to home-based exercises. After 12 months in the study group tender joint count decreased by 83,7% (p<0,01), swollen joint count – by 81,6% (p<0,01), ESR – by 72,3% (p<0,01), CRP – by 68,3% (p<0,01), pain on VAS – by 80,4% (p<0,01), DAS28 – by 44,7% (ΔDAS28=2,25±0,79, p<0,05), HAQ – by 73,8% (ΔHAQ=1,39±0,56, p<0,01), RAPID3 – by 65,1% (ΔRAPID3=6,23±1,73, p<0,01). The grip strength of a more affected hand enhanced by 48,6% (p<0,01), of a less affected – by 36,5% (p<0,05). The average extension power of a weaker knee increased by 87,3% (p<0,01), of a stronger – by 70,5% (p<0,01). The average flexion power of a more affected ankle joint elevated by 79,3% (p<0,01), of a less affected – by 74,7% (p<0,01). In the study group there were statistically significant differences from the control group in the most parameters (p<0,05), excluding CRP and DAS28 (p>0,05). After 12 months in the study group there was significantly more frequently a good response to treatment according to the EULAR criteria (DAS28) (92,6% vs 70,0% in the control group, p<0,05).Conclusions12-month complex rehabilitation improves functional ability, motion activity and quality of life, relieves pain and helps to control disease activity in biologic DMARD-treated RA patients.ReferencesForestier R, et al. Joint Bone Spine 2009;76(...