Data presented at this year’s American College of Rheumatology (ACR) meeting suggests that altering current classification criteria may lead to more effective detection of early rheumatoid arthritis (RA). Investigators at Brigham and Women’s Hospital in Boston found that including (anti-cyclic citrullinated peptide) anti-CCP testing and excluding rheumatoid nodules and radiographic changes (erosions) leads to as much as a 38 percent improved sensitivity in the detection of early RA.
       “Since we strive to diagnose RA early in an effort to determine effective, often aggressive treatment, any tool that will increase the sensitivity of diagnostic abilities would be welcomed,” maintains Alan Kivitz, MD, the head of the Altoona Arthritis and Osteoporosis Center in PA.
       The study suggests that when it comes to patients with RA symptoms of less than six months in duration, adding anti-CCP testing to current ACR diagnostic criteria increases diagnostic sensitivity for early RA from 25 to 49 percent. Dr. Kivitz and Daniel Malone, MD agree that adding anti-CCP testing to diagnostic criteria would help facilitate earlier detection of RA.
       “Specifically for the patient with early RA, the removal of nodules, which are not likely to be a manifestation of early RA, and the addition of anti-CCP, which has high predictive value, is logical and will certainly aid in the earlier detection of RA,” explains Dr. Kivitz.
       Dr. Malone points out that these criteria are typically designed to ensure that patients with RA are included in studies. The study authors agree with Dr. Malone’s assessment. They conclude that the criteria change would allow researchers to include a larger number of patients in further RA studies. They state that adding anti-CCP testing and removing rheumatoid nodules and radiographic changes from current diagnostic criteria increases diagnostic sensitivity, principally among patients with less than six months of symptoms of RA. In fact, diagnostic sensitivity with the study authors’ revised criteria increased from 25 to 63 percent among patients who had symptoms of less than six months in duration.

Could Revised Criteria Be Beneficial In Clinical Practice?

“In every day practice, RA is still a clinical diagnosis based on history, physical exam and labs and X-rays, along with the clinician's judgment,” adds Dr. Malone.
       Regardless, both Drs. Kivitz and Malone say using anti-CCP testing to assist with early RA detection is “very helpful.” Dr. Kivitz says “high-titer CCP has powerful predictive value of more active and potentially aggressive RA.” He adds that such a diagnostic tool can help facilitate a more aggressive approach to therapeutic intervention when appropriate.
       Dr. Kivitz adds that magnetic resonance imaging (MRI) could play a role in aiding the diagnosis of early RA in the near future. In select circumstances, Dr. Kivitz uses MRI in his clinic to confirm clinical suspicion of early synovitis and erosive change.

Etanercept May Prompt Clinical Remission Of Active Early RA
By Aaron Becker, Associate Editor

New data presented at the ACR suggests that etanercept (Enbrel, Wyeth) in combination with methotrexate may aid in remission of early RA more effectively than methotrexate alone.
       “Remission is the most important outcome,” states Paul Emery, MD, FRCP, an Arc Professor of Rheumatology at the Molecular Medicine Unit in the University of Leeds in the United Kingdom. “For the first time, a study has shown that remission can be used as a primary outcome.”
       In the randomized, double-blind study, the combination of etanercept and methotrexate led to clinical remission at one year in 50 percent of patients with active early RA in comparison to 28 percent taking methotrexate alone.
       In terms of secondary endpoints such as ACR 50 and ACR 70 scores, researchers also found favorable outcomes with the combination of etanercept and methotrexate. For example, 48 percent of patients receiving the combination of the two drugs achieved an ACR 70 score at one year in comparison to 28 percent of those taking methotrexate as a monotherapy. Seventy-one percent of patients receiving the combination of etanercept and methotrexate achieved an ACR 50 score in comparison to 49 percent taking methotrexate as a monotherapy.
       The study authors also noted no significant difference in infection rates or adverse events among the combination or methotrexate study groups. They conceded that the most common adverse events consisted of injection site reaction, infection and headache. They found no incidence of tuberculosis or demyelinating disease.
       Dr. Emery does point out that clinicians may run into reimbursement limitations if they try to employ etanercept earlier in the treatment armamentarium for early RA. However, he says the data from this study is promising.
       “The combination of safety — equivalent to that of placebo — and striking efficacy is unique,” notes Dr. Emery.

Is Milnacipran A Viable Option For Fibromyalgia?
By Aaron Becker, Associate Editor

Two studies recently presented at the ACR demonstrated multiple benefits with the use of the norepinephrine serotonin reuptake inhibitor milnacipran for patients with fibromyalgia.
       One study revealed that milnacipran 100 mg and 200 mg daily demonstrated significant reductions in pain and fatigue associated with fibromyalgia, as well as improved physical function at 15 weeks. A separate, phase III study, involving nearly 450 patients with fibromyalgia, found that milnacipran had sustained efficacy for patients who completed treatment for one year.
       According to Philip Mease, MD, neuropeptide modulation seems to “have a beneficial effect for pain as well as mood disorder, fatigue and possibly cognition” in patients with fibromyalgia.
       While traditional medications like amitriptyline have been “poorly tolerated,” Dr. Mease says newer medications like milnacipran “are much better” in terms of patient tolerance and seem to be more effective. Dr. Mease, an investigator for both studies, notes the studies demonstrated similar results when it came to pain improvement with milnacipran treatment.
       “Since patients respond differently to different medications, I think there is plenty of room in this large group of patients for several medicines, including both milnacipran and duloxetine, as well as other emerging neuromodulatory meds,” explains Dr. Mease, the Chief of Rheumatology Clinical Research at the Swedish Hospital Medical Center in Seattle.
       “We then typically use agents such as pregabalin in addition, knowing that these other medications have a different MOA and there may be added benefit by using combinations of drugs, both for better control of pain but in treating other domains such as sleep in the case of pregabalin.”
       Dr. Mease, a Clinical Professor at the University Of Washington School Of Medicine, says clinicians should counsel patients about their expectations in regard to pain improvement while they are taking neuropeptide modulators like milnacipran. He adds that slight nausea after initial dosing should dissipate after continued use.
       “These are not like the anti-tumor necrosis factor agents in rheumatoid arthritis,” cautions Dr. Mease. “The results are solid and helpful to the patient but patients will still have some symptoms and need multi-modal therapy, including exercise, etc. Patients may also need combinations with other medications.”

Can A Human Anti-TNF Drug Help Alleviate PsA Symptoms?
By Aaron Becker, Associate Editor

A recent Phase III study of golimumab (Centocor) presented at the aforementioned ACR meeting suggests that the human anti-TNF agent can maintain improvement when it comes to skin and joint symptoms of psoriatic arthritis (PsA).
       Philip Mease, MD, a co-investigator in the study, points out that anti-TNF medications are the best options for treating “all domains in PsA.” Additionally, Arthur Kavanaugh, MD, a lead investigator of the study, notes that human anti-TNF agents “may possibly have advantages in terms of tolerance.”
       By utilizing a fully human anti-TNF, clinicians are not likely to have the kind of issues that may result from the use of antichimeric antibodies that may reduce efficacy, explains Dr. Mease.
       In terms of efficacy, 51 percent of patients with active PsA treated with golimumab 50 mg and 45 percent treated with golimumab 100 mg achieved at least an ACR 20 response after 14 weeks of treatment. Patients also showed sustained improvements through 24 weeks of treatment, according to the study. Drs. Kavanaugh and Mease note these results are comparable to studies of other anti-TNF medications for PsA.
       While researchers continue to study other medications for the treatment of PsA, Dr. Mease notes that none of the preliminary findings from these trials have matched the efficacy demonstrated by anti-TNF modalities.
       “None of the trials with older oral disease modifying antirheumatic drugs (DMARDs), trials with two of the co-stimulatory blockade of T cell signaling agents, alefacept or efalizumab, nor the newest kid on the block, the anti IL-12/23 agent, ustekinumab, have shown similar efficacy,” claims Dr. Mease.
       If approved by the FDA, golimumab would be dosed monthly, a frequency that Drs. Kavanaugh and Mease acknowledge may have its advantages.
       “Less frequent dosing could offer an advantage for a number of patients,” says Dr. Kavanaugh, a Professor of Medicine in the Division of Rheumatology, Allergy and Immunology at the University of California in San Diego.
       Dr. Mease concurs, noting the added convenience for patients who travel a bit or those who “would like to put the presence of the disease in the back of their minds.”

Long-Term Study Looks At Adalimumab’s Effect On Spinal Mobility In Patients With AS
By Aaron Becker, Associate Editor

Another study presented at the recent ACR meeting assessed the long-term impact of adalimumab on spinal mobility in patients with anklyosing spondylitis (AS).
       Researchers revealed that adalimumab facilitated statistically significant improvement in spinal mobility at 24 weeks. The study also found that 75 percent of patients had sustained efficacy after two years of treatment.
       Charles Moxin, MPAS, PA-C notes these results are consistent with his own clinical experience with adalimumab and other anti-TNF medications.
       “The results of this study demonstrate that adalimumab is an effective treatment modality for ankylosing spondylitis and significantly improves spinal mobility in the majority of patients,” notes Moxin, a Past President of the Association of Family Practice Physician Assistants.
       The Phase III study consisted of a 236-week open label period following a 24-week double-blind period. Patients within the study had a mean Bath AS Disease Activity Index (BASDAI) score of 6.3 at baseline and had AS for an average of 10 years. Researchers measured patient progress via cervical rotation, intermalleolar distance, lumbar flexion, lumbar side flexion and other measures. The study authors also note that all patients within the study had an inadequate response to at least one non-steroidal a ntiinflammatory drug (NSAID).
       When it comes to more advanced cases of AS, Moxin says he will initiate adalimumab as a primary medication on a biweekly dosing regimen. He notes that taking this approach allows one to increase the dosing frequency to weekly and use this medication in addition to other medications as needed.
       However, in regard to mild cases of AS, Moxin suggests keeping the treatment regimen as simple as possible. He says medications such as indomethacin can “still control the symptoms and afford quality of life.”
       For most patients with AS, Moxin says physical therapy and a routine exercise program are “essential in maintaining spinal mobility and posture” in addition to medical regimens.

Is Cetrolizumab Pegol A Better Option For RA?
By Aaron Becker, Associate Editor

Results from two recent Phase III studies presented at the aforementioned ACR meeting reveal that the combination of cetrolizumab pegol and methotrexate led to significant improvements of the signs and symptoms associated with rheumatoid arthritis (RA) after 24 weeks. Researchers also noted sustained efficacy at one year of treatment.
       Nathan Wei, MD, says cetrolizumab pegol (Cimzia, UCB), a PEGylated anti-TNF drug, is a “promising new therapy” for RA.
       “The theory is that the pegalation prolongs the duration of action of the drug within the joint, leading to better efficacy and that the pegalation may also reduce some of the potential side effects of TNF inhibitors,” explains Dr. Wei, the Clinical Director of the Arthritis and Osteoporosis Center in Frederick, Md.
       The study authors also note that less than five percent of patients discontinued therapy due to adverse events. Dr. Wei explains that a small number of adverse events with anti-TNF use include infection and allergic reaction. However, he explains that the largest reason for discontinuation of any anti-TNF medication is an inadequate or waning response.
       Dr. Wei concedes he is unsure where cetrolizumab pegol would fit into a clinician’s armamentarium for RA. He points out that many rheumatologists will try two anti-TNF modalities before going to a second-line agent. If certolizumab pegol receives FDA approval, Dr. Wei suggests that the drug may become one of the two anti-TNF drugs that clinicians try before moving to more aggressive therapy.
       Another study involving certolizumab pegol found that the administration of the drug every two weeks with methotrexate demonstrated significant efficacy in inhibiting the progression of structural joint damage at six months and at one year.
       Dr. Wei acknowledges the promise of this new data but points out that both studies stand among a wealth of ongoing research and emerging developments in regard to RA treatment.

Study Reveals Benefits Of Adalimumab After Anti-TNF Failure
By Aaron Becker, Associate Editor

Results from multiple Phase IIIb studies presented at the recent ACR meeting show promising findings for the use of adalimumab in patients with anklyosing spondylitis (AS), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) who have failed a previous anti-TNF medication.
       Study authors concluded that switching to adalimumab 40 mg sc after previous anti-TNF failure during anklyosing spondylitis (AS), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treatment was effective and well tolerated among 1,291 patients. The patients studied had discontinued anti-TNF therapy in the ReAct, STEREO and RHAPSODY trials.
       “I believe that most clinicians have a strong feeling regarding TNF medications for RA, PsA and AS at this point in our experience with these drugs,” notes Don Flinn, PA-C, a physician assistant with the McBride Clinic in Oklahoma City. “We either strongly favor the use of anti-TNF medications or take a much more conservative approach, and see what will happen over the next several years as more long-term studies emerge on anti-TNF therapies and the incidence of infections, solid tumors, medication failures.”
       The study authors also revealed that patients within the three trials with previous exposure to the anti-TNF medications etanercept (Enbrel, Wyeth) and infliximab (Remicade, Centocor) had a greater disease activity than patients without prior anti-TNF treatment.
       The researchers also note comparable safety data with the use of adalimumab in patients who had previously failed anti-TNF therapy and patients without prior anti-TNF therapy. The study authors also concluded that the frequency and severity of adverse events were consistent with adalimumab’s current safety profile. They note that adverse events among this large study population were too low for a logistical analysis.
       In regard to when clinicians may consider switching anti-TNF agents, Flinn says it always depends upon the individual patient’s clinical response.
       He emphasizes assessment of the affected joints for tenderness and swelling, as well as obtaining CRP and ESR measures. Once one has obtained all the information from these objective measurements, Flinn says clinicians must subsequently make a subjective determination of how well the patient is doing with his or her treatment regimen.

Study Suggests Long-Term Efficacy Of Abatacept For RA
By Aaron Becker, Associate Editor

Five-year cumulative data recently presented at the aforementioned ACR meeting revealed that the combination of abatacept (Orencia, Bristol-Myers Squibb) with methotrexate offers long-term efficacy and safety for RA patients who previously had an inadequate response to methotrexate alone.
       Joel Kremer, MD, one of the study investigators, notes that nearly 50 percent of his RA patients have an inadequate response to methotrexate as a monotherapy. He typically responds by adding another disease modifying antirheumatic drug (DMARD) or a biologic agent.
       The study was conducted as an open-label extension of a Phase IIb trial. Out of the 219 patients who entered the open-label extension of the trial, 130 patients remained in the trial at five years. Ninety-one of these patients were originally randomized to the abatacept group while 39 patients were originally in the placebo group.
       According to the study authors, the combination of abatacept and methotrexate offered sustained improvement in the signs and symptoms of RA, as well as improved physical function among patients who previously failed methotrexate. Over 33 percent of the patients in the 10 mg/kg abatacept group achieved an ACR 70 score at year five.
       Additionally, nearly 60 percent of patients were still in the study after five years of abatacept therapy. Dr. Kremer notes this degree of long-term patient retention is very significant.
       “Abatacept is a reasonable addition to our therapeutic armamentarium for RA,” notes Dr. Kremer, the Director of Research at the Center for Rheumatology and Pfaff Family Professor of Medicine at Albany Medical College in Albany, N.Y.
       The study authors saw no increase in adverse events during the cumulative five-year extension of the study. However, they do report 12 autoimmune disorders in 12 patients with the most common being psoriasis and cutaneous vasculitis.

Study Reveals Potential Of Newly Approved Topical Gel For Hand OA
By Aaron Becker, Associate Editor

Recent results of an eight-week study in 385 patients over the age of 40 with osteoarthritis (OA) of the hand reveal the promise of diclofenac sodium gel 1%.
       According to the poster abstract presented at the aforementioned ACR conference, 47.7 percent of patients treated with the topical gel (Voltaren Gel, Novartis) reported a significant reduction in pain after eight weeks of treatment.
       “Most therapies for hand OA are problematic for adverse effects or lack of effectiveness,” points out Roy Altman, MD, the lead author of the study. “The success of diclofenac sodium gel 1% is demonstrated in this trial.”
       Given the study findings and the fact that diclofenac sodium gel 1% recently became the only FDA-approved topical prescription for OA pain relief in the joints of the hands, Dr. Altman says he would add this modality to his armamentarium for hand OA. However, he says clinicians should advise patients about the proper use of the medication.
       “The clinician needs to be specific in the instructions on how and when to apply the gel,” recommends Dr. Altman, a Professor of Medicine in the Division of Rheumatology and Immunology at the University of California at Los Angeles (UCLA). “Patients need to be advised of the uncommon but real risk of skin reaction, which is usually mild and only for the initial applications.”
       Michael Rudzinski, PA-C, RPh, notes that while 47.7 percent of treated patients rated diclofenac sodium gel 1% as very good or excellent in the study, 36.5 percent of placebo-treated patients gave the same response.
       While Rudzinski has observed “modest efficacy” from using topical treatments for his patients with hand OA at the Buffalo Veterans Affairs Medical Center in Buffalo, N.Y., he would like to know more regarding the cost of the treatment before he considers adding diclofenac sodium gel 1% to his armamentarium for hand OA.

Studies Suggest Tocilizumab Is Effective After DMARD Failure
By Aaron Becker, Associate Editor

Two recently presented Phase III trials of tocilizumab (Actemra, Roche) reveal that the IL-6 inhibitor may be effective in treating RA patients with an inadequate response to disease modifying antirheumatic drugs (DMARDs).
       One of the studies that was presented at the recent ACR conference found that 61 percent of patients receiving a combination of tocilizumab and background DMARD therapy achieved an ACR 20 score at 24 weeks in comparison to 25 percent of patients in the placebo group.
       Mark Genovese, MD, a lead investigator of the TOWARD trial, says tocilizumab (Actemra, Roche) represents a novel approach to reducing the signs and symptoms of RA.
       “Tocilizumab is very effective inhibiting IL-6 via blockade of the IL-6 receptor,” says Dr. Genovese, an Associate Professor of Medicine at the Stanford University School of Medicine. “It reduces C-reactive protein (CRP) to a normal range very rapidly and has significant effects on improvement in symptoms and signs.”
       The TOWARD trial was a 1,216 patient, two-arm, double-blind, placebo controlled study in which patients received tocilizumab 8 mg/kg intravenously every four weeks in addition to weekly-dosed DMARDs.
       The second study, the OPTION trial, placed 623 patients on intravenous tocilizumab (4 mg/kg or 8 mg/kg) every four weeks plus weekly methotrexate or placebo infusions plus methotrexate. Twenty-eight percent of patients treated with tocilizumab plus methotrexate achieved disease remission compared to one percent of patients treated with methotrexate alone.
       Dr. Genovese says tocilizumab may be a viable option when patients with RA have failed to have an adequate response to DMARDs.
       “Inadequate response to disease modifying antirheumatic drugs (DMARDs) is pervasive,” notes Dr. Genovese. “Most patients have mild or moderate benefits with traditional DMARDs, with few achieving remission. Many patients will lose benefits over time or develop side effects.”
       Side effects associated with tocilizumab include respiratory tract infections, headache, nasopharyngitis and hypertension, according to the study. If tocilizumab receives FDA approval, Dr. Genovese says clinicians should carefully weigh the risks and benefits of tocilizumab as they would with any therapy.