Me, My MS and I


Copaxone (Glatiramer Acetate)

 

This is a post I drafted in July and then apparently completely forgot about it! After taking Copaxone daily for 9 months I unfortunately became very allergic to one of the ingredients or the preservative included in the injection solution and suffered anaphylaxis, and as a result have now stopped Copaxone. This is a very rare allergic reaction, happening in only a small number of people. Until the reaction, I was incredibly happy on Copaxone and felt it was working well for me as I only had one relapse after about 6 months, so still wanted to publish this post, albeit it very late!

Copaxone is composed of 4 amino acids found in basic myelin protein and derives its name (Glatiremer Acetate) from these: glutamic acid, lysine, alanine, and tyrosine. Copaxone is an immunomodulator used to treat relapsing remitting multiple sclerosis. Myelin is the substance which covers nerves in the central nervous system (CNS) and which is ‘attacked’ by multiple sclerosis.

Injecting Copaxone moderates the immune system, changing the population of T cells from Th1 pro-inflammatory cells to Th2 regulatory cells, which suppress any inflammatory response in the immune system.  It is suspected that because Copaxone is similar to myelin, it may act as a ‘distraction’ for the immune system, diverting its attention from attacking the myelin in the CNS to the Copaxone being injected. However, there is no noticeable difference to the integrity of the blood-brain barrier whilst being treated with Copaxone. Although Copaxone increases the number of Th2 regulatory cells, there is no evidence that it suppresses immunity to bacteria and viruses, as it simply re-stabilises the immune system towards an anti-inflammatory response as opposed to the inflammatory response around the myelin associated with multiple sclerosis.

Copaxone is part of a group of treatments for multiple sclerosis called Disease Modifying Therapies (DMTs) but is not Interferon Beta based and does not work in the same way as the other CRAB drugs (Rebif, Avonex and Betaseron) which are Interferon Beta based. Monthly blood tests are not required to monitor liver function when taking Copaxone, but are required when taking any of the other DMTs.

In order to be offered Copaxone, you must meet the following criteria:

  • You have been diagnosed with MS
  • You must be able to walk independently with an EDSS of 5.5 or less for glatiramer acetate, meaning that you must be able to walk at least 100m without assistance
  • You must have experienced at least two clinically significant relapses in the last 2 years

Benefits

The severity and frequency of relapses has been shown to be reduced in clinical trials whilst Copaxone is being administered, making it an effective medication for managing relapsing remitting multiple sclerosis.

In the largest clinical study, the relapse rate of the group was reduced by 32% compared to a placebo treatment. It generally takes around 9 months for the full benefits of Copaxone to become apparent. In the long term (Copaxone usage of 10 years), patients average one relapse every 5 years.

Side Effects

Common side effects:

 

  • erythema (redness at injection site)
  • pain for several minutes at the injection site post injection
  • swelling at injection site
  • lumps around injection site
  • inflammation
  • chills
  • a temperature

Less common side effects:

  • flushing of the face and chest
  • tightness in the chest
  • shortness of breath
  • rapid heart beat or palpitations

These less common symptoms are also known as Immediate Post Injection Reaction (IPIR), usually resulting from accidental injection directly into a vein.

Injecting

Copaxone is administered via subcutaneous (below the skin) injections. The needle is inserted roughly 5-7mm into the skin. It is painless as the needle is thin (22 gauge) and isn’t going deep enough to enter muscle tissue.

An autoinjector is supplied with the first lot of syringes and can be used to inject rather than injecting manually. The syringe is loaded into the autoinjector and it fires the needle into the skin and depresses the plunger, administering the Copaxone. I have a medical background and decided from the beginning never to use the autoinjector as my injection technique is good.

The autoinjector is useful for those who are afraid of injecting themselves or who suffer from reduced mobility in their hands, but I feel it’s a little brutal when introducing the needle under the skin, removes control over the injection, and may lead to bruising around the injection site. If you’re able to, it’s worth considering having your MS nurse train you how to inject manually rather than with the autoinjector.

Injection Rotation

Copaxone is administered via daily 1ml subcutaneous injections. Injections sites must be rotated, with 7 different areas around the body as designated injection sites. Rotation of injection sites and areas of injection within those sites is essential to prevent permanent hardening of the skin or lipoatrophy (loss of subcutaneous tissue).

The 7 separate sites are:

  • Upper left arm
  • Upper right arm
  • Abdomen
  • Left hip
  • Right hip
  • Left thigh
  • Right thigh

There is no correct order to rotate through these sites in, you will find an order that suits you. You must inject in a different site each day for 7 days.

Injection Sites

A diary is provided to note down where you inject each day, and has space to note any problems.

Copaxone Injection Diary

Hints and Tips

Establish a good daily routine and perform your injection at the same time every day when your energy levels are highest (e.g. when coming home from work, when getting up in the morning, lunch time). It’s easy to forget to inject, and establishing a good routine forms a good habit of injecting at the same time each day and means you’re much less likely to forget.

Set an alarm on your phone for injection time every day. Injecting will very quickly become second nature and you shouldn’t need this for long.

The gel pad provided in your pack can be used to cool / warm the injection site either before or after injecting. You can phone and ask for an additional one should you wish to warm / cool beforehand and do the opposite post injection. It’ll take some experimentation to find which is the best combination for you, or if you need to warm / cool the site at all. I find it easier not to heat or cool either pre- or post injection.

Take your syringe out of the fridge 20 – 30 minutes prior to injection to allow the liquid to warm to room temperature as cold fluid injected into the body can be uncomfortable.

Warm the syringe to body temperature in your hand immediately prior to injection – this can also help to reduce any discomfort.

Always inject at a 90 degree angle to the body.

Immediately after the injection, apply firm pressure with a cotton wool ball to the injection site for 30 – 60 seconds to minimise any bruising or discomfort.

Do not rub the injection site.

Do not inject into scar tissue or stretch marks.

Avoid injecting an area where clothes, such as waistbands, will rub.

Avoid injecting after a hot bath or shower, or exercising.

Note in your injection diary any tips that you find make injecting easier, and also note any issues to speak to your MS nurse about.

The abdomen injection sites are anywhere further than 5cm from the navel. Point your index finger at your navel, and your second knuckle is approximately 5cm from your navel. Anywhere outside of this is suitable to inject in.

When flying, Copaxone must be taken on board in hand luggage as it would freeze in the luggage hold and be unusable. You can obtain a letter from your consultant to show to the airline and security at the airport stating that the medication must be taken in hand luggage and is safe.

If you require travel sharps boxes or cool bags / packs for travelling with your Copaxone, the distribution company which delivers your medication will supply these free of charge if you phone and request them.

If any fluid escapes the needle prior to injection, tap the syringe to remove the fluid.

Do not remove the air bubble from the syringe – they’re designed to be injected.

How effective is Copaxone?

Evidence supporting the effectiveness of glatiramer acetate in decreasing the frequency of relapses in patients with Relapsing-Remitting Multiple Sclerosis (RR MS) derives from two placebo-controlled trials, both of which used a glatiramer acetate dose of 20 mg/day. (No other dose or dosing regimen has been studied in placebo-controlled trials of RR MS).1 A comparative trial of the approved 20 mg dose and the 40 mg dose showed no significant difference in efficacy between these doses2.

In its pivotal trial 3 of 251 patients, after 2 years Copaxone failed to show any advantage in halting disability progression (78% of treated patients were Progression-free versus 75% Progression-free on placebo).

However, a 2004 Cochrane Medical review4 pointed out that “Glatiramer acetate did not show any beneficial effect on the main outcome measures in MS, i.e. disease progression, and it does not substantially affect the risk of clinical relapses.”

As a result5, the FDA marketing label for Copaxone does not as yet have an indication for reducing the progression of disability.

On February 25, 2010, a long-term study on Copaxone was published in the February issue of the journal Multiple Sclerosis. It was the longest prospective and continuous evaluation ever conducted in relapsing-remitting multiple sclerosis. The fifteen-year clinical study showed that more than 80 percent of patients were still walking without assistance, despite a mean MS disease duration of 22 years, and two-thirds of the patients have not as yet transitioned to secondary progressive MS. Patients who remained in the study over 15 years showed a reduction in relapse rate from baseline, as well as minimal increase on the Expanded Disability Status Scale (EDSS.) It also established the long-term safety profile associated with Copaxone. 6

In 2 recent studies, both reported at the 2007 ECTRIMS meeting, the efficacy of glatiramer acetate was compared to high-dose/high-frequency interferon beta. In the REGARD study, Rebif was compared to glatiramer, and in the BEYOND study, Betaseron was compared to glatiramer. In both trials, there was no significant difference between interferon and glatiramer in the primary endpoints (time to relapse) or in any clinical endpoints, although some differences in MRI measures of disease activity have been claimed.

A recent study by the Department of Neurology at The University of Texas Health Science Center argues that a double-blind three year study failed to demonstrate a treatment effect of Glatiramer acetate on Primary-Progressive Multiple Sclerosis.7

In February, 2009, the FDA approved an expanded indication for Copaxone “for reduction of the frequency of relapses in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), including patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.” 8

The expansion of Copaxone’s indication to include patients with a Clinically Isolated Syndrome (CIS) is based on a clinical trial (PreCISe) which showed that Copaxone delayed the progression from the first clinical event to Clinically Definite Multiple Sclerosis (CDMS) in a statistically significant and clinically meaningful manner, corresponding to a risk reduction of 45%. The proportion of patients who converted to CDMS was 43% for the placebo group and 25% in the Copaxone group. 9

The Bits ‘n’ Pieces

 

Sealed Syringe

 

 

Copaxone Syringe

L - R: Travel Sharps Boxes, Main Sharps Box

Heat / Cool Pack

Syringe Organiser

Autoinjector

References

http://www.weizmann.ac.il/ICS/booklet/1/pdf/copaxon.pdf

http://www.mult-sclerosis.org/Copaxone.html

‘Confidence With Copaxone’ booklet.

Wikipedia.

1. http://www.copaxone.com/pdf/PrescribingInformation.pdf

2. the 9006 trial; Cohen JA et al. Neurology. 2007;68:939-944)

3. FDA marketing label – http://www.copaxone.com/pdf/PrescribingInformation.pdf

4. Cochrane Medical review of Copaxone – http://www.cochrane.org/reviews/en/ab004678.html

5. Copaxone marketing materials - http://www.copaxone.com/NewlyDiagnosed/pivotTrial.aspx

6. The study “Continuous Long-Term Immunomodulatory Therapy in Relapsing Multiple Sclerosis: Results from the 15-Year Analysis of the U.S. Prospective Open-label Study of Glatiramer Acetate,” a follow-up to the pivotal, Phase III trial, followed 100 ongoing Copaxone® (glatiramer acetate injection) patients starting in 1991. Patients’ EDSS scores were evaluated every six months. Confirmed disability progression was defined as ‰¥1.0 EDSS point increase sustained for six months. Patients were classified as “stable/improved” if EDSS score changes were less or equal to 0.5 points. Proportions of patients who reached confirmed thresholds of EDSS 4, 6, or 8 while on Copaxone®, and Kaplan-Meier (KM) estimates of median times to these thresholds, were obtained. http://www.mscare.org/cmsc/Informs-Copaxone-Demonstrates-Robust-Long-Term-Efficacy-and-Safety.html

7. Wolinsky J, Narayana P, O’Connor P et al. (2007). “Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial”. Ann Neurol 61 (1): 14–24. doi:10.1002/ana.21079. PMID 17262850.

8. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020622s057lbl.pdf

9. http://www.medicalnewstoday.com/articles/90768.php



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