Medications - DMARD (Non-biologic)

Welcome A newbies Guide to PsA
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Disease-modifying antirheumatic drugs (DMARDs) are a group of medications commonly used in patients with arthritis. They work to decrease pain and inflammation, to reduce or prevent joint damage, and to preserve the structure and function of the joints. The choice of DMARD depends on a number of factors, including the stage and severity of the joint condition, the balance between possible side effects and expected benefits, and patient preference. Before you start any of the DMARDs discuss the benefits and risks of each type of therapy, including possible side effects and toxicities, dosing schedule, monitoring frequency, and expected results with your doctor.

In some cases, one DMARD is used. In others, more than one medication may be recommended. Sometimes a patient must try different medicines or combinations to find one that works best and that has the fewest side effects. A patient who does not respond completely to a single DMARD may be given a combination of DMARDs, such as methotrexate plus another medication.

The most common DMARDs are methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide.

They take effect over weeks or months and are not designed to provide immediate relief of symptoms so welcome to the”gap” usually you will start to see results at about 8 weeks.

All of us will generally have to be on one or more DMARDs at one time or another. Most insurance companies will require a trial of one or more of these drugs before starting the Biologic meds. Despite the horror stories most patients do very well with these drugs and side effects are generally temporary. It doesn't SEEM that way, but it is. below are specifics on some of the more common medications and some coping strategies.

For most of us, we find (and research supports) these meds have more effect on peripheral symptoms (hands feet elbows etc) than do the biologics. By the same token they are less effective against spinal pain. Many of us also take the DMARD’s because they have been shown to increase the life of biologic drugs.

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Minocycline (Minocin, Tetracycline)

Minocycline is an antibiotic, part of the group known as tetracyclines. It may be used to treat (RA). Although RA is not thought to be caused by an infection, minocycline may improve the signs and symptoms of RA. Minocycline belongs to the class of drugs known as DMARDs (disease-modifying anti-rheumatic drugs).

Minocycline is an antibiotic, which means it helps stop or kill bacteria that cause infections. When used to treat RA, however, minocycline works differently to control inflammation. Minocycline decreases the production of substances causing inflammation, such as prostaglandins, metalloproteinases and leukotrienes. It also increases production of interleukin-10, a substance that reduces inflammation.

It belongs to the group of tetracycline antibiotics which often are used to treat infections which is why I mention it here. There have been a number of studies involving the use of the tetracyclines as a DMARD specifically Minocycline. It has been shown that for very mild RA Minocycline is sometimes effective. Note I said RA and not PsA. There is NO study data that indicates that it is effective as a DMARD for PsA

These studies have been used by a number of groups to substantiate the validity of antibiotic treatment for RA. The Road back is one of the bigger ones. What they are doing has NOTHING to do with the DMARD action of Minocycline. They believe arthritis has an infectious cause. There is NO evidence to this effect and certainly none for Psoriatic arthritis (Anytime some one lumps all arthritis together run don’t walk)

We that have been around a while may occasionally refer to the folks who have been sucked into the low dose antibiotic treatment Smurfs as the main side effect is that Minocycline and similar give a bluish tint to the skin. The mod team (after about 10 seconds of debate) has decided that this alternative treatment and especially promotion of “The Way Back” and similar is not appropriate for this site.

While Minocycline may be a valid treatment for early and mild RA it is NOT for PsA, which is not EVER mild.

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Arava (Leflunomide)

Leflunomide, another DMARD, is a prodrug. This means it must be changed by the patient's own body into the active drug. This conversion occurs in the stomach and blood soon after the Leflunomide is taken. The effect of Leflunomide is often thought to be due to “switching off” the lymphocytes (one of the key cells causing inflammation in arthritis) that are about to attack the joints. However the reality is no one knows how DMARDs work.

Leflunomide is given in tablet form. There are several ways of starting Leflunomide. It can be given with a “loading” dose. Meaning a high dose for a few days to build the drug up to maximal strength as soon as possible, or it can be started slowly at low dose and allowed to gradually build up effect. There is a trade off between achieving rapid onsets of action and ensuring the least possible side effects. Many rheumatologists prefer to start Leflunomide slowly. Either way Leflunomide is a gap drug – it takes time to work.

Leflunomide can be given in combination with other disease modifying drugs, although there is limited data about these combinations. The combination of Leflunomide with methotrexate is more controversial. Some experts consider this to increase the risk of serious side effects, particularly liver toxicity. Others think it is safe and effective. There is also some evidence that Leflunomide can be combined with biologics in place of methotrexate, though there is a lot of doubt about its relative benefit in this situation.

Between 50% and 60% of patients get improvement of at least 20% when they are given Leflunomide for 6 and 12 months. These improvements are similar to those seen with other disease modifying drugs like methotrexate and sulfasalazine.

20% improvement with most arthritis drugs is considered success. The ACR is pushing for a minimum 50% improvement response for efficacy. This is a very controversial proposal, as it would severely limit available medications.

The number of patients who improve by 50% also increases with leflunomide, though fewer patients show such substantial benefits. One key clinical key trial published in 1999 showed that 33% of patients treated with leflunomide improved by this amount, while only 14% showed such an improvement without treatment.

Leflunomide may cause serious birth defects. If you are pregnant or are considering having a child, you should discuss this issue with your doctor before beginning this medication. For this reason, it is not often prescribed to young women. Use of an effective form of birth control is critical throughout the course of this treatment and for up to two years after it is stopped. This is important, because Leflunomide lasts in the body a long time, even after stopping the medication, and could still cause birth defects during this time.

Men taking Leflunomide should also practice birth control along with their partners as they too can pass on birth defects. There is a drug called cholestyramine—to help remove Leflunomide users systems when discontinued.

In “user reviews” MTX is rated much higher for both satisfaction and fewer side effects than is Leflunomide. Leflunomide is not a folate-depleting drug as is MTX but it does have many of the same effects. Some patients have had relief from the addition of prescription folic acid. There is also a supplement/vitamin called Metanx which is a combo of folic acid and Vitamin D that some members have reported success with

Members, who use brand name Arava vs generic Leflunomide report differences in performance between the two. As generics vary it may be worthwhile to have your pharmacist check the “Orange Book” rating of the generic he is dispensing and discuss these difference with your doc.

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METHOTREXATE (MTX)


Methotrexate is in a class of drugs called DMARDS or Disease Modifying Anti Rheumatic Drugs


Why we take it:
Methotrexate is prescribed in order to reduce the inflammation and halt the overproduction of cells at inflammation sites.It is also used in combination with certain biologic drugs to help prevent antibody formation or for patients who do not respond well to biologic therapy alone.


How it works:
For Psoriatic Arthritis: MTX suppresses the activity of enzymes in the immune system that cause inflammation; however, the exact mechanism of action is unknown.


To support certain biologic drugs: When taken with certain biologic drugs such as Remicade or Humira, it has been shown to increase the effects of the medication and to reduce potential side effects. MTX is also used to help prevent the formation of antibodies to biologic drugs by increasing the level of the medication that remains in the patient’s body. This inhibits the peak and trough effect of the biologic dosing schedule.


It can also be used in combination with most biologic drugs for patients who simply do not respond well to the biologic therapy alone.


Cost:
Methotrexate is a relatively inexpensive drug. That makes it one of the few drugs used to treat PsA that DOESN’T cost an arm and a leg.


Common Side Effects:
As with any drug, there are numerous side effects listed on the Patient Information pamphlet. However, we have listed the most common side effects reported by people taking the medication for Psoriatic Arthritis, and at the doses this population of patients usually takes. Please see your patient handout for the full list.

  • Nausea
  • Diarrhea
  • Stomach aches
  • Vomiting
  • Hair loss
  • Appetite Suppression

Special Testing & Considerations:

Women of childbearing years must have a pregnancy test prior to beginning the medication and must have a regular contraceptive method as the drug can cause serious birth defects.

Pregnant or breast feeding mothers can not use MTX.

Males are also encouraged to use condoms while they are taking MTX.

Patients must submit to periodic blood testing to monitor the complete blood count, liver and kidney functions. Liver biopsy is no longer required for routine monitoring of patients.

Your doctor may order a chest x-ray.

COMBATING SIDE EFFECTS
Pay SPECIAL ATTENTION to the details in this section. Knowing these three things can be the difference between SUCCESS with methotrexate and FAILURE.
*Some of these tips are based on the current research; others are based on anecdotal evidence and common sense. Talk to your doctor before trying anything new.*

Folic Acid Supplementation:
Methotrexate is a folate antagonist, and reduces the amount of folate in the body. This is a primary cause of the side effects associated with methotrexate. Numerous studies have found that adding a folic acid supplement to the patient’s medication therapy helps to reduce these side effects. Talk to your doctor about adding a prescription dose of folic acid if you are taking methotrexate. The BEST thing to do is to ask for the folic acid prescription when the doc hands you the prescription for the methotrexate. If you don’t have prescription insurance, folic acid supplements are available over the counter at your local pharmacy; however, to achieve any results, you will still need to take a prescription strength dose. Talk to your doctor about this.
How you take your MTX can have a big impact on the side effects that you experience.
Many people report having GI side effects with oral methotrexate. However, patients who take it via injection report much fewer GI symptoms. This might be an option for you to explore, especially if the side effects are really impacting your quality of life. The injections are self-administered at home via a very small syringe and a very tiny needle.
When to take your dose…
This is a BIG deal. As mentioned above, MTX has numerous side effects and, in some cases, these side effects can have a significant impact on quality of life. That said, planning when to take your dose is just as important as remembering to take the medication in the first place. For your first dose, take a look at your schedule for the upcoming week and plan to take it when you have the fewest activities. Most working people chose to take it on Friday evening. This way, they can sleep through the worst of it, and have the next day to recover. After you have a few doses under your belt, you will be able to see what, if any, side effects you will have and tailor your dosing schedule to best meet your needs.