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We performed a randomized, double-blind, controlled clinical trial comparing intravenous pamidronate and placebo for pain relief in recent osteoporotic vertebral compression fractures (VCF). Patients suffered from recent (<21 days), painful, osteoporosis-related VCF. They were randomized to receive daily intravenous infusions of either placebo or 30 mg pamidronate for three consecutive days (total pamidronate: 90 mg). The main criterion for efficacy was improvement in standing pain on a 100-mm visual analogical scale (VAS) at day 7. Secondary criteria were standing pain at days 3 and 30; supine pain at days 3, 7, and 30; patients' overall assessment of improvement; mobility index; and number of \"20% responders\" and \"50% responders\" (respectively, 20% and 50% improvement in standing pain at days 7 and 30). Statistical analysis with non-parametric tests was carried out on an intention to treat basis. Thirty-two patients were enrolled in the study; 16 were given placebo and 16 pamidronate. Thirty-one patients were evaluated at day 7 and 26 patients at day 30. VAS pain decreased significantly in both groups at day 7 (placebo -23 mm, pamidronate -42 mm, p<0.01). The difference in pain scores between groups was -23.25 mm (confidence interval (CI) [-42.3; -4.2], p=0.018) at day 7 and -26 mm at day 30 (p=0.03), in favor of pamidronate. At day 7, there were 4 versus 12 \"50% responders,\" respectively, in the placebo and in the pamidronate groups (likelihood ratio: 8.372; p=0.004) and 9 versus 14 \"20% responders\" (likelihood ratio: 4.038; p=0.044). At day 30, there were 5 versus 10 \"50% responders,\" respectively, in the placebo and in the pamidronate groups, and 7 versus 11 \"20% responders.\" Patients' overall assessment of improvement at day 7 was 37+/-26 mm in the placebo group and 59+/-30 mm in the pamidronate group (p=0.019), and 42+/-26 mm and 72+/-21 mm at day 30 (p=0.07). The two groups did not differ significantly at days 7 and 30 for supine pain, Schober index, or finger-ground distance. No significant adverse reaction related to treatment occurred. Pamidronate provides rapid and sustained pain relief in patients with acute painful osteoporotic VCF and is well tolerated. Further investigations are needed to better define the place of pamidronate in the management of painful recent osteoporotic collapse.

ObjectivesAnti-drug antibodies (ADA) are responsible for decreased adalimumab efficacy in axial spondyloarthritis (SpA). We aimed to evaluate the ability of methotrexate (MTX) to decrease adalimumab immunisation.MethodsA total of 110 patients eligible to receive adalimumab 40 mg subcutaneously (s.c.) every other week were randomised (1:1 ratio) to receive, 2 weeks before adalimumab (W-2) and weekly, MTX 10 mg s.c. (MTX+) or not (MTX−). ADA detection and adalimumab serum concentration were assessed at weeks 4 (W4), 8 (W8), 12 (W12) and 26 (W26) after starting adalimumab (W0). The primary outcome was the proportion of patients with ADA at W26. Four years after the study completion, we retrospectively analysed adalimumab maintenance in relation with MTX co-treatment duration.ResultsWe analysed data for 107 patients (MTX+; n=52; MTX-; n=55). ADA were detected at W26 in 39/107 (36.4%) patients: 13/52 (25%) in the MTX+ group and 26/55 (47.3%) in the MTX− group (p=0.03). Adalimumab concentration was significantly higher in the MTX+ than MTX− group at W4, W8, W12 and W26. The two groups did not differ in adverse events or efficacy. In the follow-up study, MTX co-treatment >W26 versus no MTX or ≤W26 was significantly associated with adalimumab long-term maintenance (p=0.04).ConclusionMTX reduces the immunogenicity and ameliorate the pharmacokinetics of adalimumab in axial SpA. A prolonged co-treatment of MTX>W26 seems to increase adalimumab long-term maintenance.

BackgroundTNF inhibitors are effective in treating spondyloarthritis (SpA). However, anti-drug antibodies (ADA) may be responsible for decreased efficacy. Methotrexate reduces adalimumab immunogenicity in rheumatoid arthritis (1).ObjectivesThe aim of the study was to evaluate the effect of methotrexate on ADA detection in SpA patients receiving adalimumab.MethodsOne hundred and ten SpA patients eligible for adalimumab 40 mg S/C eow were randomized on a 1:1 ratio to receive MTX 10 mg s/c every week, 2 weeks prior (V0) adalimumab (MTX+), or adalimumab alone (MTX-). ADA detection and adalimumab concentration were assessed 4 weeks (V2), 8 weeks (V3), 12 weeks (V4) and 26 weeks (V5) after starting adalimumab (V1). The main outcome was the percentage of positive patients for ADA detection at V5 or last available visit.ResultsPatients' characteristics (sex, previous TNF inhibitors, disease duration, HLA B27 +/-, BMI) were comparable between the two groups. One hundred and seven patients were analyzed, 55 in the MTX+ group versus 52 in the MTX- group. ADA were detected at V5, in 39/107 (36.4%) patients; 13/52 (25%) in the MTX+ group versus 26/55 (47.3%) in the MTX- group (p=0.03). Adalimumab concentrations were statistically higher in the MTX+ group as compared with the MTX- group at V2, V3, V4 and V5 (Figure 1). There was no difference in terms of adverse events and efficacy between the two groups.ConclusionsMTX reduces immunogenicity and ameliorates pharmacokinetics of adalimumab in SpA patients. The clinical impact of this combination requires longer period studies.References Krieckaert CL, Nurmohamed MT, Wolbink GJ. Ann Rheum Dis 2012. AcknowledgementsThe authors thank Bruno Giraudeau for his methodological advice in the study design; Yoann Desvignes for technical support with the study protocol; Elody Marnat for data management; Coraline Gadras and Céline Vignault for blood sample management; Anne-Claire Duveau for technical assistance. This work was promoted by the Regional University Hospital Center of Tours and supported by grants from the French Ministry for Health and Sport within the framework of the “Programme Hospitalier de Recherche Clinique 2011” and received fundings from the “Lions Club, Tours Val de France” and from Nordic Pharma who provided subcutaneous methotrexate. This work was a collaborative venture by HUGO (Hôpitaux Universitaires du Grand Ouest – Western France University Hospitals Network).Disclosure of InterestE. Ducourau: None declared, T. Rispens: None declared, E. Dernis: None declared, F. Le Guilchard: None declared, L. Andras: None declared, A. Perdriger: None declared, E. Lespessailles Grant/research support from: MSD, Novartis, UCB, Pfizer, Consultant for: MSD, Novartis, UCB, Pfizer, A. Martin: None declared, G. Cormier: None declared, T. Armingeat: None declared, V. Devauchelle-Pensec: None declared, E. Solau-Gervais: None declared, B. Le Goff: None declared, A. de Vries: None declared, E. Piver: None declared, D. Ternant Consultant for: Sanofi, Amgen, P. Goupille Consultant for: Abbvie, Biogaran, BMS, Hospira, Janssen, MSD, Pfizer, Sanofi-Genzyme, UCB, D. Mulleman Grant/research support from: Nordic Pharma, Abbvie, Consultant for: MSD, Novartis, UCB, Pfizer