Background to the BSRBR-RA
The BSRBR-RA initial goals were to recruit and follow up 4000 patients treated with each of the first 3 anti-TNFα agents and anakinra plus a comparison group of 3900 active RA subjects treated with conventional non-biologic disease modifying anti-rheumatic drugs (nbDMARDs). These numbers of patients were chosen to provide sufficient statistical power to ascertain a doubling in risk of lymphoma (the major rare severe adverse event of concern) over 20,000 patient years of observation. The same calculation applies to any rare adverse event with a similar incidence of approximately 1/1000 person years. The original cohorts for the 3 anti-TNFα agents are now closed to recruitment but remain under long-term follow-up; less than 200 patients on anakinra were recruited, but this small group continues to be followed and has provided useful data.
More recently a cohort of 1,640 rituximab patients (recruitment closed June 2012) has been added and recruitment to two new cohorts (2,000 certolizumab pegol and 500 tocilizumab patients) are open to recruitment to the end of 2012 at the least. No cohort of abatacept patients is planned at present.
The BSRBR-RA is the largest prospective register of rheumatology patients receiving anti-TNFα therapy in the world. It currently has over 20,000 patients registered and continues to grow. Both patients and rheumatology health professionals complete BSRBR questionnaires on a 6 monthly, then annual, basis. The register is supported by a team of staff at the Arthritis Research UK Epidemiology Unit at the University of Manchester (UoM).
The original comparison cohort is a group of about 3600 active RA subjects treated with conventional non-biologic disease modifying anti-rheumatic drugs (nbDMARDs).
There is an increased risk of premature mortality, serious infection and lymphoproliferative malignancy in patients with RA and other connective tissue diseases, independent of the treatment they have received. Thus the patients most likely to receive the new biologic agents are already at increased risk of premature mortality, infection and malignancy. It is therefore fundamentally important not just to document the occurrence of these events in a treated cohort of patients, but to compare their occurrence with that which might have occurred if such patients had remained on “conventional” therapy or received a different biologic agent.
Originally the most appropriate comparison group was those patients on nbDMARDs who had never taken a biologic drug (biologic naive). However these patients are increasingly those at the milder end of the disease spectrum who have a lower background risk of all the serious adverse events (SAEs) of interest. The Register is therefore now recruiting to a new comparison cohort comprising patients exposed to agents already studied (so their safety profile is known).
The risk associated with any new biologic therapy for malignancy, lymphoproliferative malignancy, infection requiring hospitalisation, serious co-morbidity and death (events of special interest – ESI) is evaluated.