This is a opinion by some physicians treating rheumatoid arthritis patients and their personal opinions about the newer therapys being currently used .

 

For this small and admittedly unscientific survey, six rheumatologists from practices of various sizes in different geographic locations were interviewed. Some of these doctors have been involved in clinical studies of one or more of the therapies; others haven’t. What they have in common is their willingness to share their own clinical observations and opinions.

Here are their views:

CELECOXIB (Celebrex)

ROFECOXIB (Vioxx)

What they are: the first two drugs in a new class called cyclooxygenase-2 (Cox-2) inhibitors. The Cox-2 inhibitors work much like traditional nonsteroidal anti-inflammatory drugs (NSAIDs) to block pain and inflammation, but studies show they are less likely than other NSAIDs to cause stomach ulcers and bleeding. Celebrex is FDA approved for both rheumatoid arthritis (RA) and osteoarthritis (OA). Vioxx is FDA approved for OA and acute pain. Both drugs are taken orally.

Pros: All but one of our experts like to prescribe these drugs for at least some patients – typically patients who have risk factors for ulcers or who have had ulcers in the past. Some doctors, including , routinely prescribe Cox-2 inhibitors for any patient who needs high doses of NSAIDs to help manage the pain and inflammation of RA.

Cons: Doctors stressed that Cox-2s don’t influence the course of the disease, a common misconception among patients. "These are not miracle drugs," . "Their advantage is that they are less likely than traditional NSAIDs to cause ulcers."

Another physician  believes the Cox-2s’ relative safety may be overstated. He believes traditional NSAIDs would cause fewer problems if people used them properly, taking them only with meals.

All the doctors said the drugs’ costs – which are higher than the generic versions of traditional NSAIDs – as well as reimbursement limitations set by insurance companies were largely what kept them from prescribing the drugs more frequently.

Who’s getting them: people with OA or RA who require anti-inflammatory drugs yet have a history of stomach ulcers or risk factors for stomach ulcers. In some practices, anyone who needs a high dose of NSAIDs for any inflammatory disease receives a Cox-2.

Who’s not: in general, people who take low, intermittent doses of NSAIDs (such as those used to relieve OA pain) and those without a history of or risk factors for stomach ulcers.

Costs: A typical month’s supply of Celebrex (30 200-milligram [mg] capsules) costs approximately $72.60; a month’s supply of Vioxx (30 12.5-mg tablets) also costs $72.60.

ETANERCEPT (Enbrel)

What it is: the first in a class of medications called biologic agents to be approved for RA. Unlike many synthetic drugs that stifle a person’s entire immune response, biologic agents are proteins used to target certain features of the immune system specifically involved in inflammatory disease. Enbrel blocks the action of tumor necrosis factor (TNF), a chemical involved in inflammation. The drug is given twice weekly by injection with a small needle inserted just beneath the skin.

Pros: All of the doctors  interviewed gave the drug high marks for both effectiveness and relative speed of effect. "Unlike most disease-modifying drugs, Enbrel works pretty rapidly," . "The systemic features of fatigue and aching tend to respond pretty quickly, and patients do tend to feel a lot better on it."

"Its effects can be quite dramatic,". "It’s an excellent medication,". "It offers an opportunity that people haven’t had before and may make a major difference for some people." -comments.

Cons: The doctors hold off on prescribing Enbrel for a couple of reasons, the main one being cost. "If the cost were lower, I would try it a lot earlier". Another concern was the newness of the drug. "We don’t know the long-term effects because it has only recently become available"  "We certainly try to determine first if more conventional therapies will do the trick."--typical comments.

Who’s getting it: people whose RA hasn’t responded well to DMARDs such as methotrexate, sulfasalazine, gold or hydroxychloroquine; children with juvenile rheumatoid arthritis that hasn’t responded to more conventional therapy; people with insurance to cover it. Some receive Enbrel experimentally for diseases such as psoriatic arthritis, ankylosing spondylitis and lupus.

Who’s not: for now, people with early disease; people who have not yet tried other DMARDs or whose RA is controlled with traditional DMARDs; people who can’t afford it.

Cost: About $275 per week for two 25 mg injections, or some $1,190 per month.

HYALURONAN (Hyalgan)

HYLAN G-F20 (Synvisc)

What it is: hyaluronic acid substitute/viscosupplement. Both are believed to increase the quality of synovial fluid, although the mechanism by which they do this is not well understood. Both are approved for the relief of pain from knee OA and are given by injection directly into the joint (Hyalgan in a total of five injections given weekly; Synvisc in three). Although these are different products, the doctors that we interviewed tend to use them interchangeably, choosing whichever is easier to obtain at the time.

Pros: These products offer a new pain-relief option for people with OA of the knee. "I know they’re not a cure, but I see some patients get a lot of pain relief.". At least one doctor held great hope for the substitutes. "Although we don’t understand how they work, there’s a possibility that they actually stimulate [cartilage constituents] and therefore may have more of an effect than just pain relief" -- "I think that this is probably one of the more interesting things that we deal with because we really don’t have a very good [array of treatments] for osteoarthritis."

Cons: Although these products are more widely used by orthopaedic surgeons, the rheumatologists report that not all patients have good results with them. "They are not as effective as we thought they would be."--. "I don’t use them a lot because I haven’t had very good results with them."

"I have used them," ---, "but I haven’t seen any dramatic results. There are some people who say their knee symptoms are less [after these injections], but I must confess we’re not using them quite as much right now as we were initially. Patients aren’t asking for them as much as they were."

Who’s getting them: people with mild to severe OA of the knee accompanied by pain that does not respond well to acetaminophen or non-drug treatments, such as physical therapy or exercise. Studies and clinical practice show the best results occur in people with mild to moderate OA.

Who’s not: people with other forms of arthritis; people seeking relief from OA pain in joints other than the knee; people whose is pain responding well to acetaminophen and/or non-drug therapies.

Cost: A three-shot course of Synvisc costs approximately $646.92; a five-injection course of Hyalgan is $661. Either round of shots may relieve pain for as long as six months to a year. (Prices do not include the cost of having a doctor administer the injections.)

INFLIXIMAB (Remicade)

What it is: a biologic response modifier that blocks the action of tumor necrosis factor (TNF), a chemical involved in inflammation. It was previously approved for Crohn’s disease, an inflammatory disease of the bowel; it was approved for RA by the FDA..

It is administered intravenously once a month or every two months in a two-hour outpatient procedure in combination with methotrexate.

"I have one RA patient who also has Crohn’s and was prescribed Remicade by her gastroenterologist. Her RA improved as well," says one..

The rest of the doctors were open-minded about using Remicade in the future. "Remicade works a little differently [from Enbrel, which is also a biologic response modifier], so I’m sure there will be a place for it too," says another.

Cons: Doctors cited the risk of side effects as their greatest concern about Remicade "Because it’s not a completely human protein, there is potential for side effects.".

Other drawbacks cited include: It requires intravenous infusion, which can be uncomfortable and confining, and it is more expensive than most other drug treatments for RA.

Who’s getting it: people with Crohn’s disease; people with rheumatoid arthritis for whom taking methotrexate alone is not sufficiently controlling the disease.

Who’s not: people whose RA has responded to other therapies.

Cost: approximately $1,222 for each eight-week dose (actual dose is based on patient’s body weight), plus the cost of infusion.

LEFLUNOMIDE (Arava)

What it is: the first disease-modifying antirheumatic drug to be approved for RA in more than a decade. Arava affects the function of white blood cells called T lymphocytes that are involved in the inflammatory process. The drug is taken orally.

Pros: Although its mechanism of action is different, Arava offers benefits similar to those of methotrexate – and often without methotrexate’s side effects, says Dr. Furst. "For people who experience side effects such as malaise, fuzzy thinking and nausea from methotrexate, I might prescribe [Arava]," he says.

"For some patients, Arava works very well," ---. "It’s not a panacea, but it seems to help, so it seems to be worth using"..

Cons: Although doctors don’t have to try other drugs for RA before prescribing Arava, most of the doctors we questioned use it only after other options have failed. "I don’t use it as a first-line agent," ---. "I’m relatively conservative. I try the older things first and then go to the newer things if what I’ve used before doesn’t work."

For cost reasons, some doctors prefer Arava to other drugs and biologic agents such as Enbrel; however, Arava costs much more than most traditional DMARDs, such as methotrexate, one points out.

Who’s getting it: people whose RA is not responding well to other DMARDs, particularly methotrexate, alone; people who have trouble taking methotrexate because of its side effects.

Who’s not: people who are doing well on traditional DMARDs; pregnant women; in some practices, any woman of childbearing age.

Cost: Some $244 per typical month’s supply (one 20-mg tablet daily).

WHAT’S A PATIENT TO DO?

With all the new treatment options for arthritis, sorting out which one might be appropriate for you can be difficult. Generally, your physician will make the decision based largely on disease type and severity, the ability (or inability) of less expensive or more conventional drugs to control the disease, his experience with particular drugs, and the patient’s preference and – unfortunately – insurance coverage.

General experience has shown that for about two-thirds of people with arthritis, traditional drugs such as DMARDs, prednisone and NSAIDs are effective in managing the disease. If you’re among those who need something extra, these new drugs offer exciting options to replace or add to your current treatment.

If you’re taking one of the new drugs (or any drug, for that matter), it’s important that you talk with your doctor about the effects you can expect as well as the side effects you need to be aware of. If you’re not taking one of these drugs but would like to, speak to your doctor. He may consider prescribing one of them – or least tell you why he thinks he shouldn’t. If finances are a factor, ask your doctor about ways to get the medication more affordably. He may be able to put you in touch with manufacturers who provide their products at low or no cost to patients who meet certain income or insurance requirements.

Foremost, remember that no one drug will help everyone. But the drugs in this article represent seven new chances that something will work for you.

 PROSORBA THERAPY: ANOTHER NEW OPTION

One new treatment option for rheumatoid arthritis (RA) is not a drug at all. Protein A immunoadsorption (Prosorba) therapy was approved last year for the treatment of moderate to severe RA.

In the procedure, blood is drawn from one arm and passed through a cell separator machine that separates liquid (plasma) from the blood cells. The plasma is passed through a Prosorba column, where antibodies are removed. The treated plasma and blood cells are then recombined and returned to the patient through a vein in the other arm.

Prosorba therapy is administered in 12 weekly procedures, each lasting two to two-and-a half hours.

While Prosorba therapy isn’t used as widely as the new drugs, three of the doctors we interviewed said either they or their colleagues have prescribed it. The other three said they would consider using it – if the right patient were to come along.

Who’s the right patient? ----someone who has failed several DMARDs, even methotrexate."

Many such patients experience a good response with Prosorba. "Thirty to 40 percent who were on Prosorba in clinical trials had good results," says a doctor, who was involved in clinical trials of the therapy. In fact, some people experienced a remission of RA that lasted up to a year or more, he says. "And these were people who had not been helped by anything else."

"This is not for the everyday patient," says a researcher, who was also involved in a Prosorba trial. The main reason doctors say they limit Prosorba to more severe cases is these are the cases for which it is FDA approved – and about which there are scientific data supporting its use.

Other reasons for not prescribing Prosorba therapy earlier include its cost (approximately $1,500 per treatment – or a total of $18,000 for the 12-week course) and the fact that it "is time-intensive and it requires effort and discomfort for the patient".  Furthermore, some patients don’t experience any response until 16 to 20 weeks into the treatment (although the majority respond in nine to 12 weeks).

Nevertheless, for people who aren’t helped by conventional drug therapies, the commitment to Prosorba may be one well worth making, the doctors say

Unlike most forms of arthritis, RA usually begins when people are in their 20s or 30s. In many cases, the resulting fatigue from the illness forces people to change or quit their jobs.

"It's important to keep these people working, so they can live their lives normally," says Dr. John Klippel, medical director for the Arthritis Foundation.

Researchers from Finland presented the findings at the annual scientific meeting of the American College of Rheumatology, which concludes today in New Orleans.

The researchers tracked 162 patients for five years at the Lappeenranta Central Hospital in Finland. For the first two years, half of the patients received a combination of drugs while the other half received a single drug. Then, for the last three years, all of the patients could choose to be treated with a combination of drugs, including methotrexate and sulfasalazine.

Those who got just a single drug early on had an average of almost three times as many sick days during the five years as those with the more aggressive treatments -- 32 days a year compared to 12. While all of the patients could work at the start of the study, 29 percent of the first group had retired by the end, compared to 20 percent of the second group, says lead researcher Dr. Kari Puolakka.

More aggressive therapy not only improves the quality of life for RA patients, Puolakka says, it also "saves substantially the costs to society." Disability benefits for the single-drug group cost the Finnish government almost 900 Euros (about $900) a year, compared to just over 300 Euros (about $300) a year for the group that received a mix of medications, she says.

In America, the study confirms a recent shift in treatment methods from a single drug to a combination of drugs, Klippel says.

Adalimumab (D2E7), an investigational drug, appears to be effective in long term treatment of rheumatoid arthritis (RA) when used alone or in combination with methotrexate.

The finding was presented here October 28 at the annual meeting of the American College of Rheumatology (ACR).

Dr. Gerd Burmester, from the University of Charite, in Berlin, Germany, presented data from a two-year study testing the efficacy of adalimumab monotherapy for the treatment of patients with RA who were refractory to treatment with at least two previous disease modifying anti-RA drugs (DMARDs). Adalimumab is the first human anti-TNFa monoclonal antibody being tested for treatment of rheumatoid arthritis.

The study consisted of two parts: a 12 week placebo-controlled, double-blind multi-dose trial period (20 mg, 40 mg or 80 mg weekly) followed by a 40 week follow-up period in which patients who had been randomised into the placebo arm were switched to a 40 mg per week adalimumab. All of the patients then entered a 12-month open label period.

Of the 229 patients who entered the second 12-month period, 205 (89.5 percent) completed the trial. Nine patients withdrew due to adverse effects, seven due to a lack of efficacy and eight for non-medical reasons. Of the seven serious adverse effects, three were lung infections including one case of tuberculosis, a complication, which has been seen with other TNF inhibitors.

Patient response to adalimumab was rapid and remained constant between the first and second year, regardless of whether the end point measure was Health Assessment Questionnaire (HAQ) status, number of joints that were swollen or tender, or ACR (American College of Rheumatology) 20 criteria.

For example, at baseline, the mean HAQ score was 1.70 for all patients, by 12 months it had dropped to 1.12 and at 24 months it was still 1.12. Similarly, when the end point measured was ACR20, 79 percent patients achieved such improvement at one year and 76 percent at two years; for ACR70 the numbers are 21 percent and 24 percent for one year and two years, respectively.

This consistent level of response is what makes biologic drugs so valuable, said Dr. Burmester. "I think this is extremely important, the most important aspect of biologics," he told Doctor's Guide.

In a related three-year study, researchers in The Netherlands and Germany have followed patients who were originally enrolled in a phase I trial and have now taken adalimumab for three years in an open-label continuation trial.

Of the 54 patients enrolled in the original trial, 42 (79 percent) have continued on the medication for three years. All patients were on a standard dose of methotrexate at the time of enrollment (mean 16 mg per week) and have continued on that dose throughout the three-year period.

As in the previous trial, these patients responded rapidly to adalimumab and achieved maximal response within twelve months. Their response has remained stable throughout the trial. For example, at baseline patients had a mean number of 12 tender joints, at one year that number was reduced to three and was down to two by three years. Similarly, the mean HAQ score dropped to 1.00 at one year from 1.42 at baseline and remained 1.00 at three years.

The dose of adalimumab in both trials is currently 40 mg injected subcutaneously every other week, though it has varied some during the course of the studies.

Both studies were supported by Abbott Laboratories.