Short-term data regarding the immunogenicity of monoclonal antibodies and the effect on treatment response have been reported for several conditions such as inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis, psoriasis, and multiple sclerosis and for several therapeutics such as infliximab, adalimumab, and natalizumab. Three of 76 patients (4%) with antiadalimumab antibodies achieved sustained remission compared with 67 of 196 (34%) antiadalimumab antibody–negative ones patients with antiadalimumab antibodies less often achieved remission (DAS28 < 2.6 HR, 7.1 95% CI, 2.1-23.4 P < .001) compared with antiadalimumab antibody–negative ones.Ĭonclusion Among outpatients with RA in whom adalimumab was started over 3 years, the development of antidrug antibodies was associated with lower adalimumab concentration and lower likelihood of minimal disease activity or clinical remission. Ninety-five of 196 patients (48%) without antiadalimumab antibodies had minimal disease activity vs 10 of 76 patients (13%) with antiadalimumab antibodies patients with antiadalimumab antibodies less often had sustained minimal disease activity score in 28 joints (DAS28) (< 3.2 HR, 3.6 95% CI, 1.8-7.2 P < .001) compared with antiadalimumab antibody–negative ones. Patients with antiadalimumab antibodies more often discontinued participation due to treatment failure (n = 29 hazard ratio, 3.0 95% CI, 1.6-5.5 P < .001) compared with antiadalimumab antibody–negative ones (n = 28 ). Patients without antiadalimumab antibodies had much higher adalimumab concentrations (median, 12 mg/L IQR, 9-16 mg/L) compared with patients with antibody titers from 13 to 100 AU/mL (median, 5 mg/L IQR, 3-9 mg/L regression coefficient, −4.5 95% CI, −6.0 to −2.9 P < .001) and also those greater than 100 AU/mL (median, 0 mg/L IQR, 0-3 mg/L regression coefficient, −7.1 95% CI, −8.4 to −5.8 P < .001). Results After 3 years, 76 of 272 patients (28%) developed antiadalimumab antibodies-51 of these (67%) during the first 28 weeks of treatment. Treatment discontinuation, minimal disease activity, and clinical remission were compared for patients with and without antiadalimumab antibodies. Serum adalimumab concentrations and antiadalimumab antibody titers were determined after follow-up. Main Outcome Measures Disease activity was monitored and trough serum samples were obtained at baseline and 8 time points to 156 weeks. All 272 patients were diagnosed with RA and started treatment with adalimumab in an outpatient clinic. Objective To examine the course of antidrug antibody formation against fully human monoclonal antibody adalimumab and its clinical relevance during long-term (3-year) follow-up of patients with rheumatoid arthritis (RA).ĭesign, Setting, and Patients Prospective cohort study February 2004-September 2008 end of follow-up was September 2010. Little is known about the clinical relevance of antidrug antibodies against these drugs during long-term follow-up. Shared Decision Making and CommunicationĬontext Short-term data on the immunogenicity of monoclonal antibodies showed associations between the development of antidrug antibodies and diminished serum drug levels, and a diminished treatment response.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience.Challenges in Clinical Electrocardiography.Sixty-seven of 196 patients without AAA reached remission vs 3 of 76 patients with AAA. C, Indicates proportion of patients who reached sustained remission (DAS28 < 2.6) for patients with and without AAA (survival analysis, P < .001). Both curves with AAA differ significantly from the curve without AAA (survival analysis, P 100 AU/mL). A, Proportion of patients who reached sustained minimal disease activity score (DAS28 100 AU/mL).
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |