TNF inhibitors: Safer than we thought

By Dr Irwin Lim, Rheumatologist

2004 was the year I commenced my own practice as a rheumatologist. It was also the year the TNF inhibitors became available for widespread use in Australia as the government agreed to subsidise the costs heavily.

During my training, I had virtually no exposure to biologic disease-modifying agents. Sure, I was aware of some of the landmark trials but that's not quite the same as having a feel for the medication with your own patients.

It was with excitement, anticipation and a fair dose of healthy worry that I commenced my first patients on these TNF inhibitor medications.

These were reported to be potent drugs, and the name, TUMOUR NECROSIS FACTOR (TNF) , rightly or wrongly, demanded some vigilance. Inhibiting or blocking TNF may lead to bad consequences with the biggest worry being Infection and Malignancy.

The safety reports from clinical trials were important and useful, but the trials reported were too short and too restrictive in their patient selection, to really be reassuring enough.

Because rheumatologists all over the world were similarly worried, large nation-wide patient registries were set-up to track side effects of these drugs. Examples of these registries include United Kingdom's BSRBR, Sweden's ARTIS, Germany's RABBIT, Spain's BIOBADASER, Denmark's DANBIO, and USA's CORRONA. Many thousands of patients have been tracked.

10 years on, and the experience has been good. Life-changing for many patients, empowering for many rheumatologists.

And, the safety of these drugs has been better than anticipated. I'll discuss the big 2 worries in this post.

Infection

Of course, TNF inhibitors are serious drugs and they do increase the risk of serious infections. The rates however have been less than predicted.

It is important to remember that the diseases we treat with these agents, such as rheumatoid arthritis, already have a higher baseline risk of infection. Also, using the standard non-biologic disease-modifying agents (DMARDs) does also increase risk of infection, especially if higher doses of steroid (eg Prednisone) are required.

Using TNF inhibitor medications in patients who require them does lead to a slightly higher rate of serious infection. The trade-off for the expected improvement in disease control and improved long term outcomes, in a patient who unfortunately isn't doing well on standard non-biologic treatment.

The patient registry data has also shown that reactivation of tuberculosis has been reduced substantially with routine tuberculosis screening programs pre-medication use.

Malignancy

The good news is that there has been no definite signal, after a decade of widespread use, in patients all over the world, of an increase in incidence of solid cancers. By that I mean, breast cancer, colon cancer, etc.

Lymphoma was always a worry. Patients with rheumatoid arthritis already have a higher risk of lymphoma (link for more info). Again, good news. To date, there has been no increase in lymphoma seen in patients on TNF inhibitor therapy.

There is an increase in the occurrence of skin cancers. over and above, the increased risk of skin cancer seen in patients with rheumatoid arthritis treated with traditional, non-biologic DMARDs. What this means practically is that patients need to be warned and they need to have regular skin checks by a dermatologist or general practitioner skilled in this area.

So, are TNF inhibitors safe?

The answer is of course yes. Given the widespread use, the close monitoring patients receive, the extensive data collection to monitor safety.

This does not mean that we stop being vigilant. Rheumatologists will keep watching but it's a case of so far, so good.

What is your experience?