Pain Research Yielding Help for IC Patients

At the American Academy of Pain Management’s annual clinical meeting in Phoenix this month, providers learned how to integrate the latest traditional and alternative therapy into their practices. We’ll be bringing you some of their best ideas in future issues of the ICA Update. Research, too, was an important part of the meeting, with investigators presented cutting-edge pain research in poster sessions. Three of those studies were particularly important for IC patients in pain, bringing promise of a new treatment and new ways to thwart opioid side effects.

Tanezumab for IC Pain

This monoclonal antibody against nerve growth factor from Pfizer produced clinically significant reductions in pain in a study presented by ICA Medical Advisory Board member Robert Evans, MD.

The new drug has the potential to become an alternative to opioids for severe chronic pain and is being studied in other chronic pain conditions. Nevertheless, IC will be one of the conditions the company seeks FDA approval for. That’s great news for IC patients, since that may make insurance coverage easier and will certainly increase IC awareness.

The drug was given intravenously as a one-time infusion to patients who had moderate to severe IC and high pain scores. Six weeks later, when the peak effect was expected, patients who got the drug had pain scores averaging 1.4 points lower than scores of patients who got placebo. Although that doesn’t seem like much, Dr. Evans said in his patients, “it was huge. . . . They really felt significantly better.”

The study’s aim, he pointed out, wasn’t to thoroughly evaluate the drug’s effectiveness for pain. Many more IC patients will be needed for that. This phase 2a trial was a proof-of-concept study, intended to check safety and feasibility. Patients underwent careful neurologic examinations at every visit to check for side effects, which proved to be minimal. Headache and tingling (in the feet, for example) were the most common.

The next step is to try different doses to see what dose and timing is optimal, and we may be hearing more about that at the American Urological Association meeting next May. Studies of the drug in chronic prostatitis/chronic pelvic pain syndrome are also under way.

Genetic Discoveries May Remove Stigma for Patients who Need High Opioid Doses

Cytochrome P450 is a huge group of enzymes involved in metabolism, including the breakdown of drugs in the body. Changes in or variations of these enzymes play a major role in drug side effects. Now, a pain researcher has found that certain genetic variants of some of these enzymes are at play in some patients who need very high doses of opioids to get pain relief. They may help explain why large doses are needed and also explain why opioids don’t show up in the urine of some of these patients, even though they are taking the drugs properly and are not abusing or selling them.

Laboratories just beginning to be able to test for some of the cytochrome P450 genotype abnormalities. Forest Tenant, MD, DrPH, of Veract Intractable Pain Clinic in West Covina, California, had blood samples tested from nine of his patients who needed more than 1,000 mg equivalents of morphine a day to control their pain. All these patients said that the effects of their medication last a very short time.

One patient tested positive for the abnormal genotype 2D6 and three for the abnormal genotype 2C9. The patient with the 2D6 abnormality and two of those with the 2C9 abnormality showed almost no opioid in their blood, despite taking high doses of oxycodone. The three patients who used fentanyl showed extremely high concentrations in their blood. Dr. Tenant noted he had seen the 2d6 variant only in Asians. Interestingly, most of the patients with the variants were women, although tests need to be done on many more patients before we know whether these variants are more common in women than in men.

Dr. Tennant noted that there are more than 50 known genotypes of cytochrome p450, and he has tested only two so far, so a lot more research needs to be done.

New Drugs on the Way for Opioid-induced Constipation

Two drugs that thwart the constipating effects of opioids are on the way for people with chronic pain.

One, an injectable drug, is already used in Canada for patients with cancer pain, but new phase 3 studies in patients who have chronic pain and constipation because of opioids may lead to approval for patients who don’t have cancer. The drug, methylnaltrexone (Relistor) from Wyeth, blocks the effects of opioids at the mu-opioid receptor. But because the drug doesn’t cross the blood-brain barrier, the pain-relieving effects of the opioids patients are taking remain intact.

Somewhat farther off from approval is an oral drug that thwarts opioid-induced constipation by blocking the mu receptor in the gastrointestinal tract. The study of NKTR-118, from Nektar Therapeutics, was a dose-ranging study aimed at finding the optimal dose of the new pill. Patients taking the 25 mg and 50 mg once-daily doses had the frequency of their bowel movements restored to normal while they were taking from 30 to 1,000 morphine equivalent units of opioids a day.

To learn other ways of alleviating constipation, check out the ICA's free constipation fact sheet.

Posted July 18, 2012