Because incomplete follow up was generally due to recent initiation of anti\TNF therapy, we assumed absent follow up data to be missing at random. Results A total of 1198 patients receiving anti\TNF treatment met the inclusion criteria, with assessments every 4?months on average. The rate of intensification of traditional DMARD co\therapy over time was significantly higher with infliximab (hazards ratio?=?1.73 (99% confidence interval (CI) 1.19 to 2.51)) than with the two other brokers. Infliximab also showed significant dose escalation over time, with an average dose increase of +12% (99% CI 8% to 16%) after 1?12 months, and +18% (99% CI 11% to 25%) after 2?years. No significant differences in discontinuation rates were seen between the three anti\TNF brokers (ANOVA, p?=?0.67). Development of disease Tmem10 activity over time indicated a lower therapeutic response to infliximab (DAS28, p 0.001) compared with etanercept, after 6?months’ treatment. Conclusions In this populace, infliximab was associated with a higher risk of requiring intensification of DMARD co\therapy than the other anti\TNF CHAPS brokers and a significant dose escalation over time. Analysis of RA disease activity indicated a reduced therapeutic response to infliximab after the first 6?months of treatment, suggestive of acquired drug resistance. strong class=”kwd-title” Keywords: rheumatoid arthritis, antirheumatic therapy, anti\tumour necrosis CHAPS factor brokers, drug resistance New disease modifying antirheumatic drugs (DMARDs) have become available since 1999. Biological brokers, such as anti\tumour necrosis factor (anti\TNF), dramatically improve the signs CHAPS and symptoms of rheumatoid arthritis (RA) refractory to standard treatment.1,2,3 The chemical structure, pharmacokinetic properties, and specific mechanisms of TNF inhibition of available anti\TNF brokers differ: infliximab (INF) (Remicade; Centocor INC, Malvern, PA, USA) is usually a chimeric monoclonal anti\TNF antibody (human IgG/mouse F); adalimumab (ADL) (Humira; Abbott Laboratories, Illinois, USA) is usually a fully human monoclonal anti\TNF antibody; whereas etanercept (ETN) (Enbrel; Amgen, Inc, Thousand Oaks, CA, USA) is an designed TNF receptor (humanised CHAPS protein) acting as a competitive inhibitor of TNF and . The unique pharmacological properties of these brokers have been associated with different rates of opportunistic granulomatous infections4,5 and are thought to explain why some anti\TNF brokers work in some chronic inflammatory conditions and not in others.6,7 It is not known whether these differences impact their long term therapeutic effectiveness or the potential development of drug resistance in RA. In clinical practice, loss of effectiveness of long term DMARD treatment is usually a common problem.8 Acquired drug resistance or gradual drug failure has been described with most traditional DMARDs8,9,10,11 and is also starting to be recognised with anti\TNF agents.12,13 Not all patients with RA respond to the standard dosage of anti\TNF brokers14; 28C58% of all patients with RA show little response to these drugs in large randomised trials.15 CHAPS Acquired resistance to DMARD treatment in RA has been measured by analysing use of additional DMARD co\therapy,16 anti\TNF dose escalation,11 and drug discontinuation rates (drug survival).8,10,16,17,18 These outcomes reflect the common therapeutic options a physician has when faced with loss of DMARD effectiveness19: for patients not fully responsive to anti\TNF agents, physicians may increase co\therapy with traditional DMARDs, increase the anti\TNF dose, or decide to quit the current anti\TNF treatment and switch to other treatments. Dosage escalation has been observed with infliximab,19,20,21,22,23,24,25 but this may not a be valid measure of drug resistance for anti\TNF brokers without a flexible dosing regimen (ETN, ADL), in which case intensification of traditional DMARD co\therapy and drug discontinuation might be more adequate outcomes. This study aimed at investigating acquired drug resistance to anti\TNF treatments in a populace based observational cohort of patients with RA. We examined intensification of DMARD co\therapy, progressive dose escalation, and drug discontinuation rates of the three available anti\TNF brokers. In addition, we explored underlying pathways leading to these therapeutic adjustments in relationship to RA disease activity. Patients and methods Study populace Regulatory companies in Switzerland have requested continuous monitoring of all patients receiving costly biological brokers.26 The Swiss Clinical Quality Management of RA (SCQM) system27 was established by the Swiss Society of Rheumatology.
Because incomplete follow up was generally due to recent initiation of anti\TNF therapy, we assumed absent follow up data to be missing at random
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