A recently published retrospective review of randomized trials involving anti-tumor necrosis factor (TNF) agents suggests increased risks of serious infections and malignancies among patients who take these medications. However, the results of the study, which appeared in the Journal of the American Medical Association (JAMA), have been questioned by clinicians.

The meta-analysis focused on nine randomized controlled trials that involved either infliximab (Remicade, Centocor) or adalimumab (Humira, Abbott). According to the study, the total number of patients was 5,014. Published data from those trials indicate a total of 24 malignancies in nearly 3,500 patients who received at least one dose of an anti-TNF drug, and two malignancies in the 1,512 control patients. Citing the trial data, the authors of the meta-analysis note that a total of 126 patients receiving treatment had serious infections while 26 patients in the control groups had these infections.

According to the JAMA article, the authors noted that they performed the meta-analysis because previous studies were too small or too brief to accumulate enough data about possible adverse effects, and that postlicensure studies usually lack an adequate control group. Therefore, the authors noted that the extent to which anti-TNF medications increased the aforementioned risks was unclear.

A recent study has sparked controversy about potential risks of anti-TNF therapies.

Using a pooled odds ratio in comparing those treated with anti-TNF medication versus placebo patients, the researchers found a 3.3 ratio for malignancy and a 2.0 ratio for serious infection. The study also noted that malignancies were more common in patients who took higher doses of anti-TNF drugs as opposed to patients who took lower doses.

However, Eugene Mochan, PhD, DO, raises questions about the study. Dr. Mochan says it is unclear whether it was the medication, the severity of the disease or the combination of both that contributed to the side effects noted in the study. More research is needed in this regard, notes Dr. Mochan, a Professor of Family Medicine and the Associate Dean for Primary Care/Continuing Education at the Philadelphia College of Osteopathic Medicine in Philadelphia.

He also points out “key limitations” in the JAMA study. Dr. Mochan says the time of exposure to medication was not normalized with the analysis of serious infections, and there was considerable clinical heterogeneity (i.e. comorbidities, disease severity) among patients.

Overall, Dr. Mochan also adds that the study did not show anything new.

“Rheumatologists have been aware of the adverse effects of these immunomodulating agents, namely serious infections and lymphoma, since (the agents) were introduced into clinical practice and they have continuously monitored for these effects,” explains Dr. Mochan.

Ultimately, clinicians and patients have to weigh the benefits and possible risks of treatment regimens. Dr. Mochan adds that “numerous studies” have provided evidence on the efficacy of the anti-TNF medications.

In Brief
As this issue went to press, the Food and Drug Administration (FDA) accepted the filing of a supplemental Biologics License Application (sBLA) for infliximab (Remicade), according to Centocor, Inc., the manufacturer of the drug.

The sBLA is in regard to the drug’s ability to inhibit the progression of structural damage and improve physical function in patients who have active psoriatic arthritis.

Study Says: High Patient Tolerance For Acetaminophen And Naproxen
When it comes to patient tolerance to medications for osteoarthritis (OA), acetaminophen and naproxen continue to get high marks in that regard, according to a recent multicenter, randomized study published in Clinical Therapeutics.

Comparing acetaminophen (Tylenol, Johnson and Johnson) with naproxen (Aleve, Bayer) in adult patients with OA hip or knee pain, researchers of the study found that both medications were well tolerated.
Out of the 290 patients who received acetaminophen (4 g/d), 134 people completed three months of treatment, 96 people completed six months of treatment, 60 completed nine months of treatment and 55 completed a year of treatment. Patient adherence to dosing ranged between 95.5 to 98.6 percent, according to the study.

Acetaminophen and naproxen are well tolerated by patients with OA hip and knee pain, according to a new study.

Deborah A. Brown, APRN, BC, was surprised to see how well acetaminophen was tolerated by people who took up to 3 to 4 grams a day.

“This (study) is a nice tool to show patients and their families that acetaminophen is a safe and effective drug for osteoarthritis-related knee and hip pain,” notes Brown, an Orthopaedic Nurse Practitioner at the Beth Israel Deaconess Medical Center in Boston.

Out of the 291 patients who received naproxen (750 mg/d), 151 completed three months of treatment, 124 people took the medication for six months, 85 people completed nine months of treatment and 80 took the medication for a year. The study notes median dose adherence for naproxen ranged between 96.4 to 98.4 percent.

According to the authors of the study, gastrointestinal bleeding occurred in one patient in the naproxen group. Otherwise, they found no serious side effects related to the drugs. — A.L.

Emphasizing Exercise For Knee Pain
A recent analysis of 16 studies found that self-management initiatives and exercise are beneficial in managing OA in the knee.

Exercise, such as stationary cycling, reportedly has positive benefits for those with knee pain.

According to the study, which was published in the Journal of Rheumatology, researchers at San Diego State University noted that exercises (such as walking and stationary cycling) and self-management (in the form of dietary changes, etc.) have modest physical and emotional value.

Charlene Morris, MPAS, PA-C, says the study encourages her to continue what she has been doing all along: prescribing exercise for her patients.

“It gives patients a doable activity that will ultimately improve their disease and their life,” emphasizes Morris, the Past President of the Association for Family Practice Physicians. —A.L.

Low-Dose Rituximab: Is It Beneficial For RA?

Researchers have discovered that two different dosing regimens of rituximab nearly double the percentage of rheumatoid arthritis (RA) patients who achieve an ACR 20 response as opposed to those treated with a placebo.

The study, which was published in a recent issue of Arthritis and Rheumatism, involved 465 patients with moderate to severe RA symptoms and had demonstrated resistance to disease-modifying antirheumatic drugs (DMARDs). Three groups received a 1,000 mg dose of rituximab, three groups received a 500 mg dose of rituximab and three groups received a placebo, according to the study. All the groups also received an IV steroid, oral steroid or placebo. All patients also received methotrexate.

After 24 weeks, the researchers found that 54 percent of the 1,000 mg rituximab groups achieved an ACR 20 response, 55 percent of the 500 mg rituximab groups achieved an ACR 20 response and 28 percent of the placebo groups achieved that level.

According to the study, the dosing of rituximab (Rituxan, Genentech) was done in two infusions, two weeks apart. Study researchers noted that side effects were mild with headache being the most common. — A.L.