FDA approves new medication for osteoarthritis pain

FDA approval of Zorvolex was based on a double-blind placebo-controlled study which enrolled patients ≥ 40 years of age with clinically and radiographically confirmed (Kellgren-Lawrence grade II-III) hip or knee OA. Eligible patients were chronic NSAID and/or acetaminophen (APAP) users with baseline Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) pain subscale score ≥ 40 mm by visual analog scale and an osteoarthritis flare (≥ 15 mm increase in WOMAC pain subscale score following discontinuation of NSAID/APAP at screening).
Zorvolex 35 mg three times a day significantly improved WOMAC pain subscale scores from baseline at 12 weeks compared with placebo. Zorvolex 35 mg bid provided numerical improvement in pain at week 12 compared with placebo. Zorvolexc 35 mg three times a day and 35 mg twice a day improved the average total WOMAC score in treated patients over 12 weeks compared with placebo. The most frequent side effects Zorvolex-treated groups were diarrhea, headache, nausea, and constipation. The inclusion of patients with a documented requirement for analgesic therapy (osteoarthritis ‘flare’) at baseline and the high rates of rescue medication usage in the placebo group may have impacted the study outcome for the Zorvolex treatment groups.

FDA approves Otezla for psoriatic arthritis

The U.S. Food and Drug Administration approved Otezla (apremilast) to treat adults with active psoriatic arthritis (PsA) in March 2014.
PsA is a form of arthritis that affects some people with psoriasis. Most people develop psoriasis first and are later diagnosed with PsA. Joint pain, stiffness and swelling are the main signs and symptoms of PsA. Currently approved treatments for PsA include corticosteroids, tumor necrosis factor (TNF) blockers, and an interleukin-12/interleukin-23 inhibitor.
“Relief of pain and inflammation and improving physical function are important treatment goals for patients with active psoriatic arthritis,” said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “Otezla provides a new treatment option for patients suffering from this disease.”
The safety and effectiveness of Otezla, an inhibitor of phosphodieasterase-4 (PDE-4), were evaluated in three clinical trials involving 1,493 patients with active PsA. Patients treated with Otezla showed improvement in signs and symptoms of PsA, including tender and swollen joints and physical function, compared to placebo.
Patients treated with Otezla should have their weight monitored regularly by a healthcare professional. If unexplained or clinically significant weight loss occurs, the weight loss should be evaluated and discontinuation of treatment should be considered. Treatment with Otezla was also associated with an increase in reports of depression compared to placebo.
The FDA is requiring a pregnancy exposure registry as a post-marketing requirement to assess the risks to pregnant women related to Otezla exposure.
In clinical trials, the most common side effects observed in patients treated with Otezla were diarrhea, nausea, and headache.

NEWS (Sept 23rd 2014): Oral OTEZLA® (apremilast) Approved by the U.S. Food and Drug Administration for the Treatment of Patients with Moderate to Severe Plaque Psoriasis

Immunossuppressive therapy during pregnancy maybe safe to fetus

Women with chronic autoimmune diseases who take immunosuppressive medications during their first trimester of pregnancy are not putting their babies at significantly increased risk of adverse outcomes, according to a Vanderbilt study released online by the journal Arthritis and Rheumatism. The paper is one of the first to describe risks for medications used to treat autoimmune diseases when taken during pregnancy, according to first author William Cooper, M.D., MPH, Cornelius Vanderbilt Professor of Pediatrics and professor of Health Policy at Monroe Carell Jr. Children’s Hospital at Vanderbilt in Nashville, Tenn. Women with rheumatoid and psoriatic arthritis, ankylosing spondylitis, lupus, scleroderma, and inflammatory bowel disease who filled prescriptions for immunosuppressive treatments during pregnancy were included in the study. The drugs studied included hydroxychloroquine, tumor necrosis factor (TNF) inhibitors and other immunosuppressives such as sulfasalazine and azathioprine. When compared with the women who had medication treatment before, but not during, pregnancy the risk ratios for adverse fetal outcomes associated with immunosuppressive use during pregnancy were not statistically significant, the authors reported.

Recommendations on calcium intake

In an assessment of the scientific literature, reported as a perspective piece today in the New England Journal of Medicine, a UC San Francisco researcher says patients and health care practitioners should focus on getting calcium from the diet, rather than supplements, when possible. “Osteoporosis may result from inadequate calcium intake and it’s quite common for certain segments of our population, such as the elderly, to consume less than the recommend amount,” said Douglas C. Bauer, MD, UCSF professor of Medicine, Epidemiology and Biostatistics. “But a high calcium diet should be the preferred method to receive adequate amounts of the nutrient. The Institute of Medicine’s recommended dosage for post–menopausal women over the age of 50 and men over 70 is 1,200 mg per day. “If it is not possible to consume enough calcium from the diet, the use of calcium supplements is most likely safe and not associated with cardiovascular outcomes,” he said.

This article reviews recommendations regarding calcium intake and uncertainty about benefits as well as potential risks of calcium supplementation. In particular, some studies have suggested an increased cardiovascular risk, but findings have been inconsistent.

Updated systemic sclerosis criteria may help in early diagnosis

New classification criteria for systemic sclerosis have just been published and are more sensitive than the 1980 criteria, enabling earlier identification and treatment of this disabling autoimmune disease. The 2013 criteria, developed by a joint committee commissioned by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR), are published in the ACR journal, Arthritis & Rheumatism. The joint ACR–EULAR committee was led by Dr. Janet Pope from Western University, St. Joseph’s Health Care London in Ontario, Canada, and Dr. Frank van den Hoogen from St. Maartenskliniek in The Netherlands. The committee’s intent was to improve the classification of systemic sclerosis by clustering items and simplifying the weighting of the different criteria. The new criteria set was tested for specificity and sensitivity by comparing scleroderma cases with controls (patients with disorders similar to scleroderma), and validated by experts viewing cases with and without the disease. Based on the new criteria, a patient with thickening of the skin in the middle part of the fingers (from proximal to the metacarpophalangeal joints) would be classified as having systemic sclerosis, regardless of other features. If this criterion was not met, however, then seven items with varying weights would need to be assessed in order to obtain a scleroderma classification: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, pulmonary arterial hypertension and/or interstitial lung disease, Raynaud’s phenomenon, and SSc–related antibodies.

Fish Oil May Benefit Patients With Early RA

Research published online in Annals of the Rheumatic Diseases suggests that “high-dose fish oil added to a ‘treat to target’ regimen of conventional disease-modifying treatment in early rheumatoid arthritis (RA) was associated with improved outcomes.” Investigators found that, “among patients receiving fish oil in conjunction with triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine, the likelihood of treatment failure at 1 year was lower than for those given triple therapy alone (hazard ratio 0.28, 95% CI 0.12-0.63, P=0.002).” The researchers also found that “the rate of remission was significantly greater in the fish oil group than among controls (HR 2.17, 95% CI 1.07-4.42, P=0.03).”

New Injectable for Psoriatic Arthritis Approved by the FDA

The US Food and Drug Administration approved Antares Pharma Inc.’s (ATRS) injectable Otrexup, an alternative to pills for hard to treat arthritis and psoriasis cases. Antares Pharma Inc. stated that Otrexup is the first methotrexate approved by the FDA that patients can administer once a week by themselves using a disposable auto injector.
The medication is “intended for use by adults with active, severe rheumatoid arthritis or psoriasis who haven’t responded to or been able to tolerate first line therapy, and for children with active polyarticular juvenile idiopathic arthritis.” While methotrexate is also used in cancer treatment, Otrexup is not intended for that purpose.

Ustekinumab Approved for Psoriatic Arthritis

The FDA has approved ustekinumab (Stelara) alone or in combination with methotrexate for adults with psoriatic arthritis, for the treatment of psoriatic arthritis in adults, according to an announcement by Janssen Pharmaceuticals.
Approval of the drug, which targets interleukin (IL)-12 and IL-23, for this indication was based in part on results of the PSUMMIT-I trial published last June in The Lancet. In the Phase III international study, among patients with psoriatic arthritis randomized to receive either 45 mg or 90 mg of the drug subcutaneously at weeks 0, 4, and every 12 weeks thereafter, more than 40% had achieved at least ACR20 levels of joint symptom improvement by the end of a year, compared with only 23% of those on placebo. Differences were also significant for other levels of symptomatic improvement, including for symptoms of psoriasis.
Adverse events were similar for the drug and for placebo.
Similarly positive results of the subsequent PSUMMIT-II trial were reported last June at the annual meeting of the European League Against Rheumatism.
This is the first new biologic for psoriatic arthritis to be approved in a decade, a Janssen official observed in the press release.

New Safety Measures

The FDA’s new guidance for extended-release/long-acting opiods will likely impact the use of prescription and over-the-counter non-steroidal anti-inflammatory drugs.

The updated indication states that ER/LA opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

The updated indication further clarifies that, because of the risks of addiction, abuse, and misuse, even at recommended doses, and because of the greater risks of overdose and death, these drugs should be reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain; ER/LA opioid analgesics are not indicated for as-needed pain relief.

The FDA is also requiring a new boxed warning on ER/LA opioid analgesics to caution that chronic maternal use of these products during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS), which may be life-threatening. NOWS can occur in a newborn exposed to opioid drugs while in the mother’s womb. Symptoms may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.

New Safety Measures Announced for Extended-release and Long-acting Opiods

The FDA’s new guidance for extended-release/long-acting opiods will likely impact the use of prescription and over-the-counter non-steroidal anti-inflammatory drugs.

The updated indication states that ER/LA opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

The updated indication further clarifies that, because of the risks of addiction, abuse, and misuse, even at recommended doses, and because of the greater risks of overdose and death, these drugs should be reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain; ER/LA opioid analgesics are not indicated for as-needed pain relief.

The FDA is also requiring a new boxed warning on ER/LA opioid analgesics to caution that chronic maternal use of these products during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS), which may be life-threatening. NOWS can occur in a newborn exposed to opioid drugs while in the mother’s womb. Symptoms may include poor feeding, rapid breathing, trembling, and excessive or high-pitched crying.