Biological therapies : treatment outcome in RA-patients : quality of life, health economy and pharmacotherapy

Sammanfattning: Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disorder characterized by symmetric inflammation of synovial joints, leading to progressive erosion of cartilage and bone. The impact of the disease is wide, not only resulting in decreased quality of life (QoL), but also a loss of productivity and an increase in healthcare costs The aim of this thesis was to study the impact of treatment with tumour necrosis factor- alpha inhibitors (TNF-inhibitors) on patients with RA in terms of risk for adverse events, impact on work-force ability and the possibility to predict treatment outcome from early patient reported data. The work is based on three studies using data from the STURE-registry (Paper I, II, III/IV) and ARTIS combined with self-reported data from personal digital assistants (Paper II/IV). In paper I we investigated the underlying risk factors behind treatment-limiting infusion reactions to infliximab. We found that high inflammatory burden resulting in decreased function, high ESR and subsequently high disease activity together with a high number of previously failed DMARDs increased the risk of experiencing a treatment-limiting infusion reaction. However, daily low-dose prednisone was found to be protective. One important unexplained finding was that the significant decrease in treatment-limiting infusion reactions/year from 1999-2004. In paper II we investigated the impact of TNF-inhibitor treatment on work-force participation in patients with RA. At baseline patients worked a mean 20 hours/week, in an unadjusted analysis an increase of 4 hours/week was seen after 1 year of treatment followed by a yearly increase of 0.5 hours/week per year on treatment. This was confirmed in a mixed linear regression model, adjusting for confounding factors. Over five year of treatment the expected indirect cost gain corresponded to 40% of the annual anti-TNF drug cost in patients continuing treatment. In paper III/IV we wanted to explore the early treatment effects of adalimumab. We also wanted to investigate whether early patient-reported data using a personal digital assistant (PDA) could predict treatment outcome at three months and whether joint counts performed by the treating physician could be replaced with patient-reported joint counts. Improvement in pain, hand function, ability to perform basic activities, fatigue and emotional wellbeing all correlated with a favourable treatment outcome at three months. Patient-reported joint status correlated highly with physician reported joint counts both at baseline and at three months. Using a PDA (or other digital instruments) to detect patient-reported data could reveal early trends in treatment outcome and improve standard care. The inclusion of patient-reported data on joint status and other health measurements through digital solutions such as the internet would be both timesaving and give early and accurate information on the fluctuations of the patients individual disease progress without risk of recall bias. If linked to the patient records patient-reported data could give the treating physician a regular update on disease status without time consuming logistics, for both patient and physician, of a scheduled visit/phone consultation. In summary, registries and observational studies offer an excellent opportunity to study the effects of different treatment strategies in a clinically relevant setting, with full information on and naturalistic managing of concomitant medication etc. The experiences from these studies will lead to a more safe and effective use of the available agents.