When it comes to RA, a new study suggests anti-TNF drugs may lead to other autoimmune diseases.

A recently published literature review suggests a possible link between anti-tumor necrosis factor (anti-TNF) agents and the development of autoimmune diseases including systemic lupus erythematosus (SLE).

Researchers conducted a Medline search of articles for a 16-year period ranging from January 1990 to December 2006. The authors of the study, published in Medicine, found 233 cases of autoimmune disorders that developed in 226 patients after the use of anti-TNF medications. Out of those 226 patients, 105 were treated with infliximab, 96 patients with etanercept and 21 with adalimumab. The study authors note that 187 patients were being treated for rheumatoid arthritis (RA) and 92 patients in the study developed SLE.

Judith James, MD, PhD, says clinicians should be wary of reading too much into the study. She notes that many of the autoimmune diseases (such as interstitial lung disease and vasculitis) cited in the study are actually common, extraarticular manifestations of RA.

“Whether these clinical findings are just additional manifestations of the treated disorders or causally related to the given TNF-alpha inhibitor therapy is unknown,” points out Dr. James, an Adjunct Associate Professor in the Departments of Medicine and Pathology at the University of Oklahoma Health Sciences Center.

While the study authors observed a significant number of cases of SLE, Dr. James notes she has observed “only a handful” of cases in which patients developed SLE after taking anti-TNF medications, and often overlapping symptoms of other autoimmune diseases come into play.

Nathan Wei, MD, says the most common side effects he has seen with anti-TNF drugs are upper respiratory tract infections and injection site reactions. However, he notes he has had one patient who developed reactivation tuberculosis and another patient who developed a multiple sclerosis-like syndrome. To date, he has not seen any vasculitis as a side effect of anti-TNF drugs. Dr. Wei says anti-TNF medications are similar to other drugs with benefits and risks.

“The (anti-TNF medications) are capable of getting RA into remission but they may also cause potentially serious and deadly side effects,” notes Dr. Wei, a board-certified rheumatologist and the Clinical Director of the Arthritis and Osteoporosis Center in Frederick, Md.

When it comes to patients with RA, Dr. Wei says he uses anti-TNF drugs early, usually within two months of instituting methotrexate if the disease activity remains suboptimal.

Dr. James says this is an important consideration as well. As clinicians push to identify polyarticular inflammatory arthritis earlier and use anti-TNF drugs earlier in the course of the disease, Dr. James says some patients may have SLE or another autoimmune disease prior to anti-TNF treatment and just complain about the symptoms after receiving the anti-TNF drugs.

Dr. James says more evidence is needed to confirm the claims of the study.

“We need prospective evaluation of large cohorts of patients (treated and untreated in parallel) to see whether select features of autoimmunity are enriched in TNF-alpha treated patients,” notes Dr. James, a Member and Lou Kerr Chair in Biomedical Research at the Oklahoma Medical Research Foundation.

While Dr. Wei says the study results are “important and disturbing,” he notes they will not affect how he perceives the use of anti-TNF medications for RA. However, Drs. James and Wei do emphasize caution and careful follow-up monitoring when considering the use of anti-TNF drugs in patients with overlapping symptoms of RA and SLE.

Is Celecoxib The Most Cost-Effective Option For Long-Term OA?
By Aaron Becker, Associate Editor

A new study published in BMC Gastroenterology has found that celecoxib (Celebrex, Pfizer) is more cost-effective than nonselective nonsteroidal antiinflammatory drugs (nsNSAIDs) for the long-term management of osteoarthritis (OA) in patients with an average risk of upper gastrointestinal (UGI) events.

In particular, the study compared the cost-effectiveness of celecoxib 200 mg/d to a combination of diclofenac 100 mg/d and naproxen 1,000 mg/d for 60-year-old patients with moderate to severe OA requiring chronic daily NSAIDs. The study authors found that 21-year treatment costs among the initial celecoxib treatment group amounted to $10,096 while the nonselective NSAID group cost was $14,151.

A recent study found celecoxib to be more cost-effective than nsNSAIDs for long-term treatment of OA in patients with an average risk of UGI events.

Ara Dikranian, MD, agrees with the study authors that looking at short-term cost comparisons of medications does not offer a true gauge of cost-effectiveness.

“There is an overall clinical impression that long-term costs associated with celecoxib are lower,” notes Dr. Dikranian, who is in private practice at the San Diego Arthritis Medical Clinic. “Short-term cost analyses are short-sighted as many of the complications of NSAIDs may not occur until years later with the gathering of cumulative risks for GI events, such as concomitant medication use or advancing age. Celecoxib seems to mitigate many of these risks.”

Dr. Dikranian adds that the cost benefit of celecoxib “seems to be a secret” to many patients, physicians and payers.

“Most payers in managed care environments require a trial and failure of or intolerance to one or two nsNSAIDs prior to providing benefit coverage for Celebrex,” points out Dr. Dikranian. “Short-term cost savings seem to often trump long-term efficacy and safety.”

That said, Dr. Dikranian notes there are a couple of key assumptions that the study researchers made for the purposes of the study.

According to the study, researchers did not take efficacy with pain relief into account. Dr. Dikranian concurs with this assumption, noting that many rheumatologists agree “celecoxib does not provide more effective analgesia than other NSAIDs for managing OA pain.”

However, Dr. Dikranian says the study also assumes that patients will remain on the same NSAID for 21 years and that generic celecoxib will be available at a lower price in 2013.

“This does not consider that many patients may prefer to pay for a generic NSAID with or without gastroprotective agents for the next few years and then switch to generic celecoxib should they wish,” adds Dr. Dikranian.

What One Study Reveals About Etoricoxib For OA
By Aaron Becker, Associate Editor

While the Food And Drug Administration (FDA) declined to approve the use of etoricoxib for OA earlier this year, another study has emerged that shows the efficacy of the drug in treating the disease.

In a recent study published in Osteoarthritis and Cartilage, researchers assessed etoricoxib at 30 mg qd in comparison to ibuprofen 800 mg tid. The 12-week, randomized, double-blind trial involved 548 patients with OA of the knee or hip. The study patients had a median age of 63. The study authors found that etoricoxib provided superior efficacy to placebo and was comparable to ibuprofen.

Karen Duclon, MSN, ARNP-BC, says etoricoxib should be reconsidered as a treatment option for symptomatic OA.

“There are few treatment options available for patients who have higher GI risk,” notes Duclon. “Etoricoxib would be a more attractive OA treatment for patients and practitioners because of the once-a-day dosing and the GI protection of a COX-II inhibitor.”

Even if etoricoxib does receive FDA approval down the line, Mike Rudzinski, PA-C, RPh, says he would only use it after exhausting all nonpharrmacologic treatments and after topical capsaicin. If the patient had OA in a single joint, Rudzinski would consider a corticosteroid injection before using a COX-II selective agent.

Duclon says she would use etoricoxib for OA patients who have a higher GI risk and patients with acute exacerbations of OA pain, but she would restrict treatment to a two- or three-week interval. Duclon adds that etoricoxib would also be an option for patients who take warfarin as ibuprofen and conventional NSAIDs are contraindicated with anticoagulant therapy.

Why Are RA Patients Reluctant To Try New Therapies?
By Aaron Becker, Associate Editor

Despite the potential benefits of new treatment advances, clinicians often have patients who do not want to alter their current therapeutic regimen.

A recent study in Arthritis and Rheumatism confirmed this reality as approximately 64 percent of over 6,000 patients with RA polled indicated they would not change their current therapy as long as their disease did not get worse. Slightly over 77 percent of those polled said they were satisfied with their current medications.

Rick Pope, PA-C, says this is consistent with his clinical experience.

“In my practice, many established RA patients are hesitant to change anything about their therapy although we expend significant effort in educating patients about the risks and benefits of both DMARDs and biologic response modifiers,” explains Pope, the senior PA at the Arthritis Center of Connecticut in Waterbury, Ct.

When patients are reluctant to try new modalities, Rick Pope, PA-C, says diagnostic imaging results can be helpful.

Pope, the President of the Society of Physician Assistants in Rheumatology (SPAR), says cost is often an issue for the majority of his patients. How can clinicians try to overcome cost concerns? Pope emphasizes the use of diagnostic imaging to help educate patients on the disease process.

“It is imperative to bring an X-ray that (shows changes) over the past year,” advises Pope. “Show the patient the difference so he or she can understand what has happened and then redirect the conversation back to the arthritic process. Educating the patient on erosive disease in correlation with the increased risk for disability often is enough to convince the patient of the medical need.”

Zoledronic Acid Wins FDA Approval For Osteoporosis
By Aaron Becker, Associate Editor

Promising results from a recent three-year, multicenter study has led to FDA approval of zoledronic acid (Reclast, Novartis), the only yearly treatment available for post-menopausal osteoporosis.

“(Zoledronic acid) is a huge step to improving the lack of compliance (with oral bisphosphonates), thereby decreasing healthcare costs,” emphasizes Chris Recknor, MD, the Medical Director of United Osteoporosis Centers in Gainesville, Ga.

Patient compliance with osteoporosis medications has been a serious problem, according to Dr. Recknor. He notes that up to 60 percent of patients stop taking oral bisphosphonate therapy after one year and this lack of compliance has been shown to increase fracture rates. Citing a study presented at the National Osteoporosis Foundation meeting, Dr. Recknor says 20 percent of patients with osteoporosis have risk factors for adherence that are attributable to cognitive deficits.

“The approval of Reclast allows us more options for treating patients at increased risk for noncompliance because you are going to have 100 percent compliance in those patients receiving the drug,” claims Dr. Recknor, who has participated in most of the clinical trials for the drug over the past six years. Zoledronic acid is also marketed as Zometa with an approved indication for Paget’s disease.

The FDA approval for Reclast was based on the results of a recent study published in the New England Journal of Medicine. The study authors found that the yearly infusion of the intravenous drug reduces the risk of morphometric vertebral fractures by 70 percent and the risk of hip fractures by 41 percent. (See “Zoledronic Acid: A Better Option For Osteoporosis?” on page 10 in the July/August issue.)

Dr. Recknor adds that zoledronic acid is the only therapy that has been tested for fracture reduction at the dose that is being given. He says all other bisphosphonate drugs were tested for fracture reduction with a different dose than what is being given clinically.

Dr. Recknor does recommend using Tylenol pretreatment and every six to eight hours for two days after the infusion to decrease the likelihood of myalgias and flu-like symptoms he has seen in approximately 10 percent of patients.

New Study Cites Benefits Of Total Disc Replacement
By Aaron Becker, Associate Editor

When patients with degenerative lumbar disc disease cannot obtain pain relief via non-surgical means and medication, they may want to consider lumbar total disc replacement.

One recent prospective, randomized, multicenter study evaluated 286 patients and compared the ProDisc-L lumbar total disc replacement versus circumferential spinal fusion for the treatment of discogenic pain. Authors of the study, recently published in Spine, found that the ProDisc-L was safe and superior to circumferential fusion in multiple clinical measurements.

“My own patients’ results mirror those of the multicenter data,” claims Jack Zigler, MD, the lead author of the study, who is currently following 300 ProDisc-L patients at the Texas Back Institute in Plano, Tx. “My average ProDisc-L patient does better than my average fusion patient. My ProDisc-L patients generally have better motion, better function and use less medication.”

A recent study determined that arthroplasty with the ProDisc-L total disc replacement is safe and more effective than circumferential fusion.

In the study, researchers performed physical exams, neurologic exams and obtained radiographic views before and after surgery at six weeks, three, six, 12, 18 and 24 months. They also asked for patient self-assessments at each follow-up visit. According to the study, during the six-week and three month follow-up visits, ProDisc-L patients reported significantly higher SF-36 Health Survey scores. The

ProDisc-L patients also had superior neurologic success and, at 24 months, 91.8 percent of the ProDisc-L patients reported improvement in the Oswestry Low Back Pain Disability Questionnaire.

While most patients with degenerative lumbar disc disease can manage their disease through exercise, activity modification and medication, Dr. Zigler says there is a small subset of patients who have functional disability due to the disease. In those patients, Dr. Zigler explains that arthroplasty generally requires less surgery time, earlier rehabilitation and an earlier return to activity along with increased segmental motion than fusion.

The study determined that at 24 months, the ProDisc-L patients had a 51 percent improvement in the visual analog scale (VAS) pain assessment scale and their work and recreation status were significantly higher than control patients.

“These study results make me much more comfortable recommending arthroplasty to my patients if they meet the same criteria as patients who were enrolled in the study and are candidates for ‘on-label’ use,” says Dr. Zigler.

Dr. Zigler adds that the study utilized ten success parameters and was one of the most rigorous FDA studies ever done.

T-Scores: How Reliable Are They In Diagnosing Osteoporosis?
By Aaron Becker, Associate Editor

Prior to the development of bone density measures and T-scores, Kenneth G. Faulkner, MD, notes that clinicians often diagnosed osteoporosis only after related fractures had occurred.

However, a new study offers a closer look at the reliability of T-scores in helping to diagnose osteoporosis. The study, which was recently published in the Journal of Clinical Densitometry, involved nearly 2,400 Caucasian women over the age of 50 who had either normal or osteopenic spines. In regard to osteoporosis diagnosis, data analysis revealed that T-scores for the femoral neck were indeterminate for 12 percent of women and total hip T-scores were indeterminate for four percent of women.

“The take home message is that a clinician should not be overly focused on a single T-score value when deciding to treat a patient,” explains Dr. Faulkner, a co-author of the study.

Dr. Faulkner maintains that T-scores are “incredibly important” and provide a common measuring stick for helping to diagnose osteoporosis before it leads to fractures. However, he says the influence of precision and accuracy on the T-score has not been appreciated.

“Strict adherence to a rigid cut point for any diagnostic test without regard to the limits of the test as well as other risk factors is not appropriate,” emphasizes Dr. Faulkner.

Study Assesses Behavorial Therapy For Fibromyalgia
By Aaron Becker, Associate Editor

Can certain patient characteristics lead to more effective behavioral therapy for fibromyalgia patients? A recent study published in Arthritis Care And Research concluded that certain patient characteristics prior to treatment could be important in determining one’s response to behavioral therapy.

In the study, 125 fibromyalgia patients were randomly assigned to operant behavioral (OBT) or cognitive behavioral therapy (CBT) or placebo. At the 12-month follow-up, the study authors noted that 53.5 percent of the OBT group demonstrated improvements in pain intensity and 58.1 percent of the OBT group reported significant improvements in physical impairment. Prior to treatment, the OBT group’s physical impairment responders had significantly more pain behavior, physical impairment and physician visits in comparison to non-responders, according to the study.

Cognitive behavioral therapy is particularly effective in improving physical function, according to Dr. Williams.

At the 12-month follow-up, 45.2 percent of the CBT group had improvements in pain intensity and 38.1 percent of the CBT group reported improvements in physical impairment, according to the study. Study authors note that, prior to treatment, the CBT physical impairment responders had higher levels of affective diseases, lower coping and lower pain behaviors in comparison to non-responders.

Patrick Wood, MD, says the patient profiles that the study authors deemed to be predictive of behavioral therapy outcomes are “rather complicated.”

“One of the limiting factors in applying the data from this kind of study is a lack of resources for many small to mid-sized communities,” adds Dr. Wood, an Assistant Professor in the Department of Family Medicine and Comprehensive Care at Louisiana State University Health Sciences Center-Shreveport.

While Dr. Wood says it would be ideal to be able to predict which treatments a patient might best respond to given certain patient characteristics, he says some kind of screening instrument or procedure that incorporates these insights would be helpful in facilitating the prescreening of patients.

David A. Williams, PhD, says the effects of cognitive behavioral therapy on fibromyalgia are “on par” with the effects demonstrated with medication, exercise and acupuncture trials. Cognitive behavioral therapy has its most notable affect on improving physical function status, according to Dr. Williams, a cognitive behavioral therapist.

“It is likely that the diagnosis of fibromyalgia captures people with a variety of comorbid conditions and symptoms that are amenable to behavioral management,” adds Dr. Williams, an Associate Professor of Medicine/Rheumatology at the University of Michigan in Ann Arbor, Mich.

In regard to CBT, Dr. Wood has been “generally pleased with outcomes on a global level” when he has been able to connect fibromyalgia patients with qualified providers of CBT. In regard to patients with fibromyalgia, Dr. Wood says he reserves referral for CBT for those patients “whose clinical profile is clearly informed by psychological conflicts.” He says these conflicts may include childhood abuse, problematic interpersonal relationships or poor coping styles.

Aside from CBT, Dr. Wood says there are a number of strategies clinicians can employ to help patients with fibromyalgia manage their pain. He encourages light aerobic exercise, good sleep hygiene and compliance with medical regimens — even when the results may not be readily apparent.

In Brief

• Abbott Laboratories recently announced that the labeling for adalilumab (Humira) has been updated to reflect that the combination of the drug with methotrexate can inhibit irreversible joint damage in patients with RA for up to five years.

• Bristol-Myers Squibb recently announced that it has filed a supplemental biologics license application (sBLA) for abatacept (Orencia) with the FDA. According to the company, the sBLA is for the treatment of juvenile idiopathic arthritis in patients who have had an inadequate response to one or more disease modifying antirheumatic drugs (DMARDs).