17 April 2024
In this month’s eLearning spotlight, we spoke to Kimme Hyrich, Lead at the Centre for Musculoskeletal Research at The University of Manchester and Rheumatology Consultant at Manchester University NHS Trust. She talked us through biologics, cancer and how data can guide our decision-making.
Why have we been concerned about biologic drugs and cancer?
Delving into medical history, in the late 1800s, Professor William Coley observed the resolution of a sarcoma in a patient following an episode of sepsis. This led to the belief that something present at the time of infection could kill cancer cells. Whilst this was likely an oversimplification, this set the focus on decades of research by him and others
In the 1970s, Tumour Necrosis Factor (TNF) was isolated. There were even trials of TNF in patients with cancer but the therapeutic window was so narrow it was quickly abandoned as a sole therapy. The role TNF plays in cancer is likely much more complicated and likely not directly “toxic” to cancer cells, although it may have a role in the management of some malignancies.
A treatment called anti-TNF makes us nervous and there has been much attention on whether there is an association between anti-TNF and cancer development. Concerns increased following an FDA report in 2002 which described a series of lymphoma cases amongst patients receiving etanercept. This prompted large-scale observational studies to investigate this further.
What do we now know about biologic therapies and cancer?
Most of our research has focused on anti-TNF, this is the most widely used biologic and has been around the longest, which is helpful when you want to study a rare outcome such as cancer. The BSRBR-RA includes over 15,000 patients who have received anti-TNF. It is linked with data from the National Cancer Register so we can capture any cancer occurrence in this population even if patients are lost to follow-up from the study.
We have compared patients on anti-TNF to those on conventional DMARDs and haven’t identified any increased risk of lymphoma or solid organ cancers. This is similar to findings from other European registries and large data sets in the United States.
Is there an increased cancer risk in other inflammatory conditions like psoriatic arthritis or axial spondyloarthritis?
In rheumatoid arthritis, there is an increased background risk of cancer in this population, but based on a limited number of studies, the risk appears to be similar in these other conditions and there is no reason to believe it would be different.
Clinicians are often concerned about prescribing biologics in patients with RA with a history of cancer. Can the BSRBR-RA data help guide our prescribing?
Original guidelines based on expert opinion recommended a patient with a previous cancer should be cancer-free for 10 years before starting a biologic. Using the BSRBR-RA data linked to the national cancer register we have identified about 300 patients who had a prior history of cancer. We saw no overall difference in the rates of new or recurrent cancer diagnoses in these patients when we compared those starting anti-TNF with those who remained on conventional DMARDs.
Of course, this group will have been cautiously selected and many had their initial cancer some time ago. Added to the data that cancers don’t seem to develop at higher rates in those who have not had prior cancer (when comparing anti-TNF to conventional DMARDs), altogether the data are very reassuring.
How should the data shape how we discuss this with our patients?
The data is reassuring but we still need to counsel our patients, as many have concerns. All patients and all cancers are different and we need to consider, in those with prior cancer, what is the current state of their cancer and its immunosensitivity. Liaising with their oncologist regarding treatment plans is important as sometimes a biologic may be temporarily contraindicated.
We need to remember that rheumatic diseases are painful conditions, so there is also a consequence of withholding treatment for a theoretical cancer risk for when there's no evidence to support it. This data has changed the way I practice and I have a lot more confidence in prescribing biologics to these patients.
What is next for the BSRBR-RA in regards to cancer and biologic treatments?
The BSRBR is part of an international consortium called JAKPOT, this brings together data from 19 national registers and this data will be used to better understand the relationship between JAK-inhibitors and cancer.
For further reading check out the below.
Brown P, Pratt A G, Hyrich K L. Therapeutic advances in rheumatoid arthritis BMJ 2024; 384 :e070856 doi:10.1136/bmj-2022-070856
https://www.bmj.com/content/384/bmj-2022-070856