What Are Biologic Response Modifiers?

Think back to high school chemistry classes.  I remember making peanut brittle to learn about double-bonds, making ice cream to drive home the point that salt affects the freezing point, making yellow paint then pouring it down the drain and having to promise not to do that one at home since lead in paint had been banned, popping corn in a beaker during the instructor’s lecture (oh, wait, that last one wasn’t an approved activity).  I remember having multiple beakers of a substance, then adding a different chemical to each one just to see what would happen.  The investigations in chemistry lab were fascinating. 

Now there are people taking it to a whole new level.  Imagine learning the specific function of different kinds of cells, then figuring out how to influence those cell proteins.  What a cool job! 

Some researchers look at what takes place in a cell during inflammation.  There are a bunch of different proteins involved, and sometimes attacking one of those proteins makes a difference.  It reminds me of that row of beakers back in high school, dropping different chemicals in to see what would happen.  It is incredible that scientists can modify the way our cells respond (biologically) to inflammation.

Biologic response modifiers (BRMs) are a class of disease modifying anti-rheumatic drug (DMARD) that targets specific cells.  When these drugs work, the inflammation of RA is greatly reduced – which means a reduction in pain and fatigue, and less likelihood of joint damage.  I discussed them a little with my PCP the other day (more on that in a future post).

Here, then is a list of the biologic response modifiers currently available. 

Tumor Necrosis Factor Alpha Inhibitors (aka TNF-α blockers) 

  • Adalimumab (Humira) – every-other-week injection
  • Etanercept (Enbrel) – weekly injection
  • Infliximab (Remicade) – IV infusion
  • Certolizumab pegol (Cimzia) – monthly injection
  • Golimumab (Simponi) – monthly injection

Selective B-Cell Inhibitors 

  • Rituximab (Rituxan) – IV infusion (two initial doses given two weeks apart, thereafter at 16-24 weeks if needed)
  • Ofatumumab (Arzerra) – IV infusion – still in clinical trials; already approved for leukemia

Selective Costimulation Modulator 

  • Abatacept (Orencia) – IV infusion (three initial doses given two weeks apart, thereafter every four weeks

Interleukin-1 (IL-1) Inhibitor 

  • Anakinra (Kineret) – daily injection

Interleukin-6 (IL-6) Inhibitor 

  • Tocilizumab (Actemra) – injection every 4-6 weeks
    edit to note Actemra was FDA approved 1/8/10 

Two others being studied 

  • Baminercept (BG 9924) – targets lymphotoxin-beta – weekly injection
  • Denosumab (AMG 162) – targets RANK Ligand to reduce bone erosion, does not affect inflammation – twice yearly injections

Biologic Copays

Good news!  My insurance company covers both biologics mentioned by my rheumatologist.  They require pre-authorization, but I expected that.  The process is not supposed to take more than 72 hours.  I think that means I won’t be able to get a shot at my next appointment, but will have to return for another appointment.  I wonder if there’s a way to expedite the paperwork?

As a few people pointed out (I really appreciate all the help), Enbrel and Humira have a variety of assistance plans.

Humira has a copay assist plan.  Here’s the link to their FAQ page.  It really appears that their goal was only to claim they have a web page; I didn’t find it particularly helpful.  As nearly as I can tell, they require a person’s financial information before determining qualification for any assistance.  They don’t give an abundance of information on their website, and I have to wonder why the plan isn’t straightforward enough to clearly explain.

Enbrel also has a support program to help with copays.  It does not appear that financial information is required.  For people with commercial insurance (not taxpayer-funded medical care), there are no out-of-pocket costs for the first six months.  After that, a maximum of $10 copay per month.  Can that really be right?

So, if I accurately understand the information on Enbrel’s website correctly, that’s yet another reason to choose Enbrel instead of Humira.

WHEW!  I can proceed with this treatment without putting my family in the poorhouse.

Things are looking up.

For those who have the Enbrel Support CoPay Card Program,
am I understanding this correctly?  Is it really that easy?

Enbrel or Humira

Now that I’m reconciled to taking a biologic, I’m kinda wishing I’d just done it already.  If it works, I’ll get to discontinue plaquenil and sulfasalazine, which would eliminate eight pills every day!

The rheumy said either Enbrel or Humira.  I’ve been searching, and found this gem:

“Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell expression system. It consists of 934 amino acids and has an apparent molecular weight of approximately 150 kilodaltons.”
RxList

Chinese Hamster Ovary Cells?  Alrighty then.  That’s not exactly what I was hoping for when I set out to learn about Enbrel.

The rheumatologist gave me a little brochure that was supposed to contain information to help me choose between Enbrel and Humira, but it wasn’t the least bit helpful.  For one, it mentions Enbrel and Remicade, not Humira.  And it’s pretty dated.  With an opening statement that there are now two biologics approved for use in treating RA (I thought there were 8-9 with more in the works), I looked for a copyright and discovered that the brochure was nearly ten years old.

I’ve checked a few places online, and have summarized below what I’ve learned so far that seems pertinent.  Actually, I moved it to the bottom of the post, because although it was helpful when I was looking for information, now it all sounds pretty boring.

What it comes down to is that it sounds like they’re pretty comparable medications, but Chinese hamster ovary cells are needed to produce Enbrel; not for Humira.  I don’t think this is sufficient data for making an informed decision.  I might as well flip a coin.  If I could!

I’m not concerned about the possible side effects.

  • With meds:  likely to have more energy and the pain-free use my hands/wrists/elbows/shoulders/knees/feet.  Delay (hopefully halt) joint deterioration and deformity.  Chance at a semi-normal life
  • Without meds:  continued and worsening pain, extreme fatigue, probable joint deterioration and deformity, likely to need a wheelchair within 10 years (difficult in my 2-story house), small increase in the possibility of malignancies (still much less than 1%)

One advantage to Enbrel is that it has a longer track record.  One advantage to Humira is that it would mean half as many shots.  I’m still looking into the $ aspect.

Thank you, again to those of you who shared your experiences with me.  Based on what people have shared, I’m leaning toward Enbrel.

If you write about your experience with these biologics, I will gladly link your blog.
Please drop me a line.

***

General information comparing these biologics:

All vaccines should be updated prior to beginning Enbrel (the doctor didn’t mention that).  No live vaccines with either Enbrel or Humira, but annual flu shots should be fine.  I’m guessing that means I should get the chicken pox vaccine first, but I probably won’t.  And I think it’s about 13 years since my last tetanus shot, so I probably ought to get that one!

Both Enbrel and Humira are clear, colorless liquids that are injected subcutaneously.

Both Enbrel and Humira are used to treat RA, JIA, AS, PsA, and Plaque Psoriasis.  Humira is also used to treat Crohn’s.

Both Enbrel and Humira come in various forms, including pre-filled syringes and easy-to-use injector pens.  These things are easy to self-administer.

Both Enbrel and Humira should be stored in the refrigerator (not freezer) in the original carton until time to use.  Enbrel can be brought to room temperature before injecting, which is reported to lessen the sting.

The most common side effect reported by companies trying to sell both of these drugs is a mild reaction at the injection site.  OTOH, patients have had a few choice words about those injection-site reactions.  I guess the definition of a “mild reaction” depends on whether or not you’re the one experiencing it.

Since both of these drugs suppress the immune system, it should come as no surprise that people taking these medications can get infections.

Both Enbrel and Humira can be used alone, or as combination therapy with other DMARDs.  HOWEVER, Enbrel and Humira are TNF blockers; taking a TNF blocker with Kineret (an interleukin-1 receptor antagonist) increases the risk of infection.

It was once thought that this drug increased the incidence of lymphomas, then new evidence suggested that severe RA disease activity, not TNF blockers (or even DMARDs), is the risk.  According to the RxList information on these drugs, RA increases the chance of lymphoma 3-7 times the general population.  However, don’t panic because the risk is still incredibly small (less than 0.1%).

I’ve heard much about the increased risk of tuberculosis with the use of TNF-blockers, but it appears that the incidence of TB in RA patients worldwide is 0.01%, and 0.007% in the U.S. and Canada.  That doesn’t sound like a very big risk!  Plus, you’re tested for TB (and treated if positive) before beginning this med.

A new look at the data indicates that TNF-blockers might be associated with an increase in the risk of leukemia and new-onset psoriasis.  The FDA has required a new boxed warning about these risks.

Enbrel is injected weekly.  Humira is injected every-other-week.

Enbrel was approved November 2, 1998.  Humira was approved December 31, 2002.

A few places to look for further reading: