Biologics are big. Their popularity is reflected in their growing use since being introduced in 1998. Biologics have been used by more than 3 million patients worldwide. In 2013, Enbrel, Remicade and Humira accounted for nearly $30 billion in worldwide sales. In the USA, it is estimated that we will spend $220 billion on biologics by 2017.
Who Should Get a Biologic
The new 2015 ACR rheumatoid arthritis (RA) treatment guidelines have held true to the practice of using methotrexate (MTX) first, and that MTX or monotherapy DMARD therapy be preferred in patients with low disease activity. Biologics enter into consideration after an RA patient (early or established) has either moderate or high disease activity (based on a metric) and after a DMARD failure. Then you can equally choose from combination DMARDs or a TNF inhibitor (TNFi) or a non-TNF biologic, with or without MTX in no particular order. However, in the real world, there are mandates by insurers and payers as to with of these can be next used.
Dr. Ron van Vollenhoven wrote a neat and pragmatic perspective on how he uses biologics. He noted its fairly obvious when mild disease does not merit and when severe, recalcitrant begs for aggressive biologic treatments. Despite guidelines, “the choice whether to start a biologic or not can be very hard” and that a “Swedish study has demonstrated that in ... ‘borderline’ cases, experienced rheumatologists do indeed make very different choices”.
Importantly, we as a discipline need to be clear about how and when we use biologics. My simple suggestions:
- For those with active disease, know what your initial choice and second choice of therapy will be.
- Know when you prefer to start a biologic (early or late) and which is your go-to drug and why. A provocative article by Dr. Janet Pope questions our “habit” of use TNFi first is not exactly evidence based, since recent evidence that other non-TNFi biologics or JAK inhibitor may be equally or more effective.
- Know when to change – when you have given your drug/biologic for minimal (not maximal; maximal=delay) time period to demonstrate meaningful (not complete) effectiveness. I believe this should be 6-8 weeks with most of the drugs we currently rely on. If you don’t see “meaningful” responses by then, why wait around. Or are you one of those fans who will watch your team till the bitter end of the game, even when the score was 77-15 at the end of the first half. Of course they could have a miraculous come-back and you could say you were there. Nonetheless, I would demand more than a miracle and late-stage comeback to wait 4-6 month to declare a drug as “ineffective”.
- Knowing when to change mandates you follow objective outcome measures or have a predetermined goal as you start therapy.
- Pound for pound, there are no substantial differences in the safety of one biologic over another. There may be differences shown with large cohort studies but at the individual level, the same common risks and rare risks apply.
- There is very little data showing the superiority or inferiority of a biologic compared to methotrexate, combination DMARD or small-molecule DMARD choices.
- Prescribing biologics is often driven by habit and history favors the TNF inhibitors as first choices amongst those not responding to MTX or DMARD therapy. Nevertheless, there is no way of knowing whether a certain patient with uncontrolled RA (for instance) will respond best to an IL-1, IL-6, T cell or B cell inhibitor or a TNF blocker. Until a truly predictive biomarker can guide optimal biologic use, the prescriber needs to be committed to objective measures of response, frequent assessments and rapid changes (before 12 weeks, preferably at 6-8 weeks) when a meaningful is response is not achieved.
What goes with a biologic prescription?
In addition to having clarity and high standards for biologic use, you need to expect the same for the patient. This should begin with setting goals, rules and expectations for care, communication and outcomes. If the patient has hope (instilled by you) and you demonstrate command, that patient is likely to follow the path you lay down for them.
A critical issue is how to educate on biologic use given the time limitations you have with patients. There are several good sources you can refer the patient and family to – including the ACR and Arthritis Foundation websites or the manufacturers website. My solution is to offer you my version of “A Patient Guide to Biologics”.
If you go to the daily download (here) you can receive and use these educational materials for free. Given the complexity of this topic, the handout is admittedly complex. But from the 13 pages you can pick and choose what best suits you and your patient’s needs. Included is a two-page overview with tables offering a wide range of information and a six-page “Patient Guide to Biologics” that explains what biologics are, how they are made, what they do and how they are taken. Lastly, there are one-page per drug handouts on Kineret, Orencia, Rituxan or Actemra.
This week’s download is available for free on the RheumNow site under “Daily Download”. You need to sign in (if already registered) or register. Registration is take a few minutes, requires your name, location, what you do an email confirmation and you need to set a logon and password for future use. Your registration information will not be given or sold to any other commercial entity or shared with pharma or sponsors. Those who are registered can customize when and what content or emails you receive. It also entitles you to comment on articles, download slides or other content, “save” articles to your own folder and participate in future surveys.
Your comments and input on these educational materials would be greatly appreciated.