ObjectivesTo evaluate the efficacy and safety of subcutaneous golimumab as add-on therapy in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) treatment. To evaluate an intravenous plus subcutaneous (IV+SC) golimumab strategy in patients who had not attained remission.MethodsGO-MORE was an open-label, multinational, prospective study in patients with active RA in typical clinical practice settings. In part 1, patients received add-on monthly 50-mg subcutaneous golimumab for 6 months. The percentage of patients with good/moderate European League Against Rheumatism (EULAR) 28-joint disease activity score (DAS28)–erythrocyte sedimentation rate (ESR) response was compared in patient subgroups with various concurrent or previous DMARD treatments. In part 2, patients with EULAR responses but not remission were randomly assigned to receive IV+SC or subcutaneous golimumab to month 12; DAS28–ESR remission was measured.Results3366 patients were enrolled. At baseline of part 1, 3280 efficacy-evaluable patients had mean disease duration of 7.6 years and mean DAS28–ESR of 5.97 (SD=1.095). At month 6, 82.1% achieved good/moderate EULAR responses and 23.9% attained remission. When EULAR responses were analysed by the number of previously failed DMARD or the concomitant methotrexate dose, DMARD type, or corticosteroid use, no statistically significant differences were observed. Part 2 patients (N=490) who received IV+SC or subcutaneous golimumab achieved similar remission rates (∼25%). Adverse events were consistent with previous reports of golimumab and other tumour necrosis antagonists in this population.ConclusionsAdd-on monthly subcutaneous golimumab resulted in good/moderate EULAR response in most patients; 25% achieved remission after 6 more months of golimumab, but an IV+SC regimen provided no additional efficacy over the subcutaneous regimen.

Introduction: The prevalence of symptomatic knee osteoarthritis (OA) among Asians ≥65 years is estimated to double by 2040. This study was designed to evaluate the safety and efficacy of a single, 6-mL intra-articular injection of hylan G-F 20 in Indian patients with knee OA at 26 weeks through to 52 weeks.Methods: This study was an open-label, multicentre, phase 4 clinical trial. Enrolled patients (N=394) were ≥30 years old with Kellgren-Lawrence grade 1–3 OA; all patients received hylan G-F 20. WOMAC, SF-12, PTGA, and COGA scores, and OA medication use were evaluated at weeks 1, 4, 12, 26, 39, and 52 (initial treatment phase). At 26, 39, or 52 weeks, eligible patients could participate in a repeat treatment phase. McNemar-Bowkers, paired t-tests and ANOVA analyses were performed (alpha=0.05).Results: At 26 weeks, statistically significant changes from baseline were observed in all efficacy parameters, including the primary efficacy endpoint of WOMAC A1 (p<0.0001). Improvements continued for 52 weeks. No significant changes occurred in concomitant medication use. Eleven patients (2.8%) were re-injected at week 26 or 52. After repeat injection, statistically significant decreases were observed in WOMAC A1, WOMAC C and PTGA scores (p≤0.028). Twenty-three (5.8%) patients reported 26 local target knee AEs.Conclusion: Among Indian patients within this study, a 6-mL hylan G-F 20 injection was well tolerated and effective in treating symptomatic knee OA with significant long-term (1 year) improvement of outcomes. When needed, repeat treatment was safe and efficacious for 4 weeks.Trial Registration: Clinical Trial Registry of India (CTRI/2010/091/000052) www.ctri.nic.in/Clinicaltrials/login.php.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting ~ 1% of the population worldwide. The genome wide association studies on RA patients revealed linkage with 1p36 locus containing peptidyl arginine deiminase 4 (PADI4) genes. Case-control association studies and mRNA stability assays reported the association of PADI4 gene with RA in Korean and Japanese populations. However, such association was not found in Spanish population. Differences in the association of PADI4 with RA in different populations prompted the present study in Indian population. Anti-CCP antibodies, RF antibody, disease activity scores at 28 joints (DAS28) and mutations in three exons of PADI4 were investigated in RA patients and control group. Among the patients anti-CCP antibody levels were found to be associated with high DAS28 values (r = 0.4526, P < 0.0001). Polymorphism in exon-4 (padi4_104, [rs1748033]) of PADI4 showed significant association of 'C' allele with RA in the study population (P = 0.0008). Polymorphism in exon-3 (padi4_92, [rs874881]) also exhibited moderate association with the disease (P = 0.075). However, no association of the disease was found with the SNPs padi4_89 [rs11203366] and padi4_90 [rs11203367] in exon-2 of PADI4.

The efficacy and safety results with add-on golimumab were consistent between RA patients from India and outside India, despite high baseline disease activity in the Indian patients.

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Background Single 6mL intraarticular injection of hylan GF 20 is safe and effective with significant reduction in walking pain up to 52 weeks compared to baseline in this prospective, open label, multicentre study. Objectives The study aims to evaluate the efficacy and safety of 6mL intraarticular (IA) injection of hylan GF 20 over a period of 52 weeks in patients with symptomatic knee osteoarthritis (OA) in standard clinical practice. Methods This prospective, open label, multicentre (36 Indian centres) study is conducted in patients with symptomatic, predominant tibio-femoral OA (Kellgren-Lawrence grade [KLG] I–III), aged ≥30 years with moderate to severe walking pain (WOMAC A1, baseline VAS score between 40-80mm). Patients received a single 6 mL injection of hylan GF 20 at baseline and were evaluated at Weeks 1, 4, 12, 26, 39 and 52 for efficacy variables (WOMAC, SF-12, patient and clinician observer global assessments [PTGA and COGA, respectively] and impact on concomitant OA medication) and safety variables (examination of injected knee and adverse events [AEs]). The primary endpoint was change in WOMAC A1 subscore at week 26 from baseline. At week 26, 39 or 52 weeks, based on physician’s assessment of safety and efficacy during the primary phase of the study, patients were offered participation in an additional 4-week Repeat Treatment Phase to evaluate safety and short term efficacy. Results Out of 394 patients [mean age: 57.6±9.8 years; mean BMI: 27.66±4.48; female/male: 72/28%; KLG I: 5.1%; II: 38.3%; III: 56.6%] enrolled, 369 patients were evaluated at Week 52. The WOMAC A1 sub score (walking pain) significantly decreased as early as Week 1 after the injection and was down by 45.7% from 60.4±10.31mm at baseline to 32.4±18.88mm at Week 26 and 27.8±18.10 mm (-53.1%) at Week 52 (p<0.0001). WOMAC A pain and WOMAC C function scores decreased from baseline respectively of 50.8% and 45.5% at Week 52 (p<0.0001). The percentage of responders to treatment (as defined by at least 10mm reduction in WOMAC A1 score from baseline and no target knee AE) was 76.6% and 80.7% at Week 26 and 52 respectively. PTGA, COGA and quality of life (SF-12) scores also significantly improved over 52 weeks (p<0.0001). No significant change in concomitant medication usage was observed by Week 52 vs baseline. A total of 26 treatment-emergent target knee AEs were reported in 23 of 394 patients (5.8%) over 52 weeks. The most commonly reported treatment-emergent target knee AE was arthralgia (n=16; 4.1%). One patient had unrelated treatment-emergent target knee SAE of arthritis. Out of 11 patients retreated (2.8%), 6 patients were retreated at Week 26 and remaining 5 patients were retreated at Week 52. In these few patients who were retreated the second injection was found to be safe and effective 4 weeks after re-injection. Conclusions This study demonstrates that in Indian clinical practice a single 6mL IA injection of hylan GF 20 has a favourable safety profile and is effective in the treatment of symptomatic knee OA up to 1 year pos...