A recent study suggest that patients taking biologics for RA may be at a slightly increased risk for non-melatonic skin cancer.

An observational study recently published in Arthritis and Rheumatism revealed that patients taking biologic therapy for the treatment of rheumatoid arthritis (RA) have increased risks for nonmelanotic skin cancer and melanoma.

Utilizing data from the National Data Bank for Rheumatic Diseases and the United States National Cancer Institute, the study authors assessed the incidence of cancer among approximately 13,000 patients with RA. Forty-nine percent of these patients had a history of exposure to anti-TNF drugs, according to the study. The researchers found a 1.5-fold increased risk of nonmelanotic skin cancer and a 2.3-fold increased risk of melanoma among patients who took biologic therapy.

While Kevin Deane, MD, has counseled his patients about these potential risks, he says most have opted to continue anti-TNF therapy. In his clinical experience, Dr. Deane says patients with RA have had “great benefit” with anti-TNF medications and “very low morbidity” from skin cancer. That said, he does believe this study will have an impact on the prescription of biologics for RA.

“I believe physicians (will be cautious in using anti-TNF drugs), if at all, in patients with known melanoma, especially given the likelihood of the recurrence of melanoma even more than five years after the initial diagnosis and treatment, and the availability of other biologics such as rituximab,” maintains Dr. Deane, an Assistant Professor of Medicine in the Rheumatology Division at the University of Colorado at Denver.

Dr. Deane notes he has seen cases of non-melanotic skin cancer among patients treated with anti-TNF medications for RA. He says it is another issue clinicians should discuss with patients, particularly those who have a prior history of skin cancers. However, Dr. Deane says he is not sure if this concern will alter the number of patients who receive anti-TNF drugs as the morbidity of nonmelanotic skin cancer is generally quite low.

He does note there may a concern using anti-TNF medications with other conditions such as psoriasis as these patients “are already at a higher risk of skin cancer because of skin disease and the use of other therapies such as ultra-violet therapy and cyclosporine.” Aside from the slightly increased risks of melanoma and non-melanotic skin cancer, the study authors noted that “no other malignancy was associated with biologic use.”

What About The Limitations Of The Study?
The authors of the study concede that there are some limitations of their study. For example, the average exposure to biologics was three years. They maintain that analysis of the RA patients beyond three years may yield a stronger association between therapy and melanoma. The study authors also note other study limitations such as the availability of certain biologics, delayed identification of more recent cases of cancer, and cases in which patients died.

“It does not appear that the risk of cancer from combination therapy, such as methotrexate and an anti-TNF agent, was evaluated,” indicates Dr. Deane. “This may be an important issue as the use of methotrexate has been associated with a risk for skin cancer.”

Dr. Deane also notes that rituximab (Rituxan, Genentech) and abatacept (Orencia, Bristol-Myers Squibb) were not included within the study. The study authors also observed infrequent use of adalimumab among patients in the study.

Assessing The Key Take-Home Points
Dr. Deane maintains this study emphasizes the need for clinicians to obtain any history of cancer, especially melanoma, prior to initiating biologics. However, he says more studies are necessary before clinicians can apply typical screening to determine the risk for developing new melanoma among RA patients with no prior history.

He also adds that studies similar to this one may be very useful when it comes to treating patients with psoriatic arthritis as they may have a higher baseline risk due to preexisting skin disease.

Regular Physical Activity: Can It Help Prevent Knee OA?
By Aaron Becker, Associate Editor

A recent study published in Arthritis Care and Research says vigorous physical activity can have a positive effect on the knee cartilage of healthy adults with no history of knee injury or disease.

When it comes to OA knee pain, Charlene M. Morris, PA-C, recommends “mild” physical activity such as regular walking on a treadmill or soft surface.

In the study, researchers found that the frequency and duration of vigorous physical activity were associated with increased tibial cartilage. The study authors also found that weightbearing exercise was associated with increased tibial cartilage volume and reduced cartilage defects. The study involved nearly 300 healthy adults, between the ages of 50 and 79, who had no history of knee injury or osteoarthritis.

Charlene M. Morris, PA-C, says one should be cautious when it comes to the duration of physical activity

“The conundrum and paradox associated with this small study is that soft tissue is also likely to deteriorate with prolonged stressful activity,” points out Morris, a Past President of the Association of Family Practice Physician Assistants.
Morris advocates mild physical activity. She adds that minimal weight bearing and strenuous loading activities are beneficial for patients with knee OA.

“Movement and mild stress of the joints are necessary to maintain the three cornerstones of physical health: endurance, strength and flexibility,” emphasizes Morris, who is in practice in North Carolina. “One or two without the other(s) curtails self-sufficiency in this world of aging adults.”

The study also noted an association between moderate physical activity like regular walking and a lower incidence of bone marrow lesions. Morris adds that gentle walking or walking on a controlled, soft surface such as a treadmill “is superior to (walking on) hard or uneven terrain.”

Study Assesses Potential Of Autologous Proteins For OA
By Aaron Becker, Associate Editor

The efficacy of autologous, antiinflammatory protein injection may be superior to hyaluronic acid for the treatment of chronic knee osteoarthritis (OA), according to a recent study published in Biodrugs.

The study revealed that 57 percent of patients treated with autologous, antinflammatory protein injections (OrthoKline) achieved greater than a 50 percent reduction in pain six months after treatment. This was in comparison to 29 percent of patients treated with hyaluronic acid and 28 percent of those in the placebo group, according to the study.

Frank Caruso, MPS, PA-C, and Deborah Brown, APRN, BC, MSN, agree there may be potential for the new therapy, which is not yet approved by the FDA. Caruso says patients may be more compliant to the therapy. Brown suggests the therapy may have less potential for adverse reactions than hyaluronic acid given that the therapy is manufactured from the patient’s own body.

“This therapy may have increased effectiveness in terms of being more bio-available within the intraarticular environment,” explains Brown, an Orthopaedic Nurse Practitioner at the Beth Israel Deaconess Medical Center in Boston.

Caruso says his experience with viscosupplementation differs from the study findings on hyaluronic acid. Caruso, who has treated over 5,000 patients with viscosupplementation, notes he has seen “excellent overall” results. In his experience, 70 percent of patients report good relief of symptoms and greater mobility, especially when the injections are combined with a physical therapy program.

While Caruso would like to see more research on autologous, antiinflammatory protein injection therapy, he is intrigued by the modality. It may have “ …an enhanced positive effect in slowing down the degenerative process and stabilizing the effects of cartilage breakdown in the joint,” notes Caruso, who is affiliated with the Wake Forest University Baptist Medical Center.

Zoledronic Acid: Is It Beneficial For Hip Fracture Patients?
By Aaron Becker, Associate Editor

A new study suggests that zoledronic acid may benefit postmenopausal patients who had a hip fracture.

While zoledronic acid is currently indicated for osteoporosis in postmenopausal women and Paget’s disease, a recent study suggests the medication may also reduce recurrent fracture risk by 35 percent among patients who have suffered a hip fracture.

In the randomized, double-blind, placebo-controlled trial involving 1,062 patients, researchers found that new clinical fractures occurred in 8.6 percent of those treated with zoledronic acid in comparison to 13.6 percent of those in the placebo group. According to the study, which was recently published in The New England Journal of Medicine (NEJM), new nonvertebral fractures occurred in 7.6 percent of the zoledronic acid group and 10.7 percent of the placebo group.

Vicki DeNoia, NP-C, found the study results encouraging and says the use of the yearly intravenous medication would likely facilitate better compliance among patients.

“An advantage of zoledronic acid once a year would be immediate initiation of therapy after hip fracture repair before the patient leaves the hospital,” infers DeNoia, a Geriatric Nurse Educator with Meridian Quality Care in Wall, N.J.

She adds that the yearly administration may also be advantageous for frail, immobile patients, especially those in long-term care settings.

DeNoia does caution that many older patients visit their healthcare provider at least quarterly so some patients may have a mindset that yearly treatment is not enough. She also notes that the NEJM study did not involve a comparison with other bisphosphonates such as ibandronate sodium (Boniva, Roche).

DeNoia praised the use of vitamin D and calcium supplementation, which researchers provided to all patients in the study.

“Unfortunately, this is not done consistently, if at all, by many healthcare providers,” adds DeNoia, a board-certified nurse practitioner who is affiliated with Riverview Medical Associates in Tinton Falls, N.J.

Can Daily Risedronate Help Reduce Recurrent Hip Fractures?
By Aaron Becker, Associate Editor

New data presented at the annual American Society for Bone and Mineral Research meeting revealed that daily risedronate 5 mg may also reduce recurrent hip fractures in women with postmenopausal osteoporosis.

The study involved 339 postmenopausal women (between the ages of 70 and 79) with low bone mineral density and a history of at least one hip fracture. This subgroup of patients was drawn from a larger, previously published study that assessed the ability of daily risedronate to reduce fracture risk, according to Michael McClung, MD, a primary investigator on the study.

Researchers provided the patients with risedronate 2.5 mg daily, risedronate 5 mg daily or a placebo treatment. Over a three-year period, the study researchers found a 50 percent reduction in clinical fracture risk in those groups treated with risedronate (Actonel, Proctor and Gamble).

Dr. McClung notes the current study found that risedronate facilitated a level of fracture protection for women with prior hip fracture that was similar to what researchers had seen in the original study. Dr. McClung, the Founding Director of the Oregon Osteoporosis Center in Portland, Ore., says these results are consistent with his own clinical experience.

Kiplee Bell, PA-C, MS, says her own clinical experience with risedronate in this patient population is mixed. When it comes to geriatric postmenopausal patients with previous hip fracture, Bell says these patients usually demonstrate that “their bone health is refractory to bisphosphonates.” In these cases, Bell says she will add an exogenous hormone like Forteo (Eli Lilly), provided there are no contraindications, as well as Vitamin D.

Bell, who is affiliated with Clinical Care Associates in Philadelphia, adds that she has seen fractures among patients taking alendronate in addition to those taking risedronate. However, in her experience, alendronate has better efficacy in regard to additional fracture prevention.

Bell and Dr. McClung agree that ensuring vitamin D intake and minimizing fall risk are beneficial.

Study Cites Adjunctive Benefit Of Proton Pump Inhibitors
By Aaron Becker, Associate Editor

A recent study published in Gastroenterology found that co-administration of proton pump inhibitors (PPIs) with traditional non-steroidal antiinflammatory drugs (NSAIDs) reduces the risk of peptic ulcer hospitalizations by 54 percent.

For the purposes of the study, researchers assessed peptic ulcer hospitalizations among Tennessee Medicaid patients — between 1996 and 2004 — who had used a traditional NSAID as monotherapy or a coxib drug with or without adjunctive therapy for gastrointestinal (GI) protection. The study was co-sponsored by the Department of Health and Human Services’ Agency for Healthcare Research and Quality.

Adjunctive use of proton pump inhibitors with NSAIDs may reduce peptic ulcer hospitalizations.

The authors of the study suggest that adjunctive use of a PPI with an NSAID is equally effective as using a coxib when it comes to reducing GI issues due to NSAIDs.

Blaine Carmichael, MPAS, PA-C, a co-founder and Past President of the Riverwalk Clinic in San Antonio, Tx., says he rarely sees GI complications when he prescribing NSAIDs for patients. In 30 years of practice, Carmichael recalls only one patient who experienced GI issues with NSAIDs, and that was with aspirin.

Carmichael notes he has seen the benefit of PPI use for a variety of situations.

“I put patients on proton pump inhibitors if they have a history of peptic ulcer disease or if they are over 60 years of age,” says Carmichael. “I also prescribe a proton pump inhibitor if I am starting someone on indomethacin (Indocin) for gout.”

Can Combination Therapy With Infliximab Effectively Treat JRA?
By Aaron Becker, Associate Editor

In his clinical experience, Daniel Lovell, MD, MPH, says less than half of patients being treated with monotherapy methotrexate for active juvenile rheumatoid arthritis (JRA) exhibit an adequate response to therapy.

Dr. Lovell is the co-author of a recent Arthritis and Rheumatism study that assessed the safety and efficacy of combining infliximab (Remicade, Centocor) with methotrexate among JRA patients with an inadequate response to methotrexate by itself.

Authors of the study, which involved 122 children with persistent polyarticular JRA who had failed to respond to methotrexate, did not see significant differences in efficacy between the infliximab-treated groups and the placebo-treated group at three months. However, at week 16, when all study patients were receiving infliximab, 73.2 percent of patients achieved an ACR Pedi 30 response, according to the study. The study authors also noted “durable efficacy” at one year with both doses of infliximab.

“Infliximab is an effective treatment in polyarticular JRA. (In regard to) patients in whom compliance with outpatient therapy is an issue, infliximab is an excellent choice,” notes Dr. Lovell, an Associate Director in the Division of Rheumatology and a Professor of Pediatrics at the Cincinnati Children’s Hospital Medical Center. “This study demonstrated that over 70 percent of children will show an excellent clinical response to infliximab.”

However, Edward Giannini, MSc, DrPH, a co-author of the study, wonders whether the findings will eventually translate into clinical application.

Dr. Giannini, a Professor of Pediatrics in the Division of Rheumatology at the Cincinnati Children’s Hospital Medical Center, cites the advent of newer biologics, such as adalimumab (Humira, Abbott) and abatacept (Orencia, Bristol-Myers Squibb). (Editor’s note: Manufacturers of these drugs have submitted to the FDA for an additional pediatric indication.)

Dr. Giannini says insurance companies suspect that Centocor will not file for a JRA indication. “Thus, the physician’s ability to prescribe infliximab ‘off-label’ and have insurance cover the treatment is declining rapidly.”

While the study authors found that infliximab was predominantly well tolerated, they found more serious adverse events and infusion reactions in the group treated with infliximab 3 mg/kg than the group treated with infliximab 6 mg/kg. Dr. Lovell says the infusion reactions were mild, adding that all anti-TNF drugs have shown “very acceptable safety profiles” in children with polyarticular JRA.