Rheumatology News

NEWS 6

R heumatology N ews • Vol. 4 • No. 1 • 2016

Wearable device offers home- based knee OA pain relief

US FDA announces new plan to combat opioid abuse BY ALICIA GALLEGOS Frontline Medical News US Food and Drug Administra- tion officials are calling for a sweeping overhaul of the agency’s approach to opioid medications, in- cluding renewed efforts to improve how opioids are approved, labelled, and prescribed. The initiative focuses on new policies to help reverse the opioid abuse epidemic, while still provid- ing patients in pain with access to effective relief, Dr Robert M. Califf, FDA deputy commissioner for medi- cal products and tobacco, said in a Feb. 4 announcement. “Things are getting worse, not better, with the epidemic of opioid misuse, abuse and dependence,” said Dr Califf, who has been nomi- nated but not confirmed as FDA commissioner. “It’s time we all took a step back to look at what is work- ing and what we need to change to impact this crisis.” Under the new plan, the FDA will convene an advisory committee be- fore approving new drug applications for opioids that do not have abuse- deterrent properties and develop changes to immediate-release opioid labeling. The agency also plans to expand access to abuse-deterrent formulations of opioid products and improve the availability of naloxone and medication-assisted treatment options for patients with opioid use disorders. In a Feb. 4 editorial published in the New England Journal of Medicine , Dr Califf noted that the number of annual deaths from opioid overdoses now exceeds the number of annual deaths from mo- tor vehicle accidents (doi:10.1056/ NEJMsr1601307). “Regardless of whether we view these issues from the perspective of patients, physicians, or regula- tors, the status quo is clearly not acceptable,” Dr Califf wrote in the editorial. “As the public health agency responsible for oversight of pharmaceutical safety and effective- ness, we recognise that this crisis demands solutions. We are commit- ted to action, and we urge others to join us.” perspective of patients, physicians, or regulators, the status quo is clearly not acceptable. Regardless of whether we view these issues from the

week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose. The safety profile of secukinumab in the present studies was consistent with previous studies of secukinum- ab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr Baeten and his associates said. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondy- litis, and they validate inhibition of this cytokine as a potential thera- peutic approach, the study authors concluded. The study was sponsored by Novartis Pharma. Dr Baeten has received a grant fromNovartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis. reduced 25.5% with the PEMF device and 3.6% with the placebo device. The standardised treatment effect size induced by PEMF therapy was –0.73 (95% confidence interval, –1.24 to –0.19), the investigators reported. WOMAC pain subscale and total scores fell 23.4% and 18.4% with the PEMF device versus a 2.3% reduc- tion for both scores with the placebo device. The standardised effect size was –0.61 for WOMAC pain (95% CI, –1.12 to –0.09) and –0.34 for WOMAC total score (95% CI, –0.85 to 0.17). At 1month, the mean Short Form-36 physical health score was significantly better in the PEMF group than in the placebo group (55.8 vs 53.1; P = 0.024), while SF-36 mental health scores were nearly identical (43.8 vs 43.6; P = 0.6). Patients were allowed per protocol to take prescribed analgesic therapy as needed, but eight patients from the PEMF group stopped these medica- tions, while one patient from the pla- cebo group stopped medication and three started a new therapy for chronic pain. No adverse events were reported during the study. “Given that our data are limited to a low number of participants and the long-term efficacy of the wearable de- vice is unknown, the generalisability of the results needs to be confirmed in a larger clinical trial with a longer dura- tion of treatment,” Dr Bagnato and his coauthors concluded. “However, the use of a wearable PEMF therapy in knee OA can be considered as an alternative safe and effective therapy in knee OA, providing the possibility for home-based management of pain, compared with previous studies.”

BY NICOLA GARRETT Frontline Medical News From the New England Journal of Medicine S ecukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine . The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr Dominique Baeten of the Academic Medical Centre at the University of Amsterdam and his colleagues ( N Engl J Med 2015 Dec 23. doi: 10.1056/NEJMoa1505066). “Although head-to-head trials would be required to fully assess the efficacy and safety of secuki- numab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response crite- ria] response rates achieved with secukinumab at week 16 in our studies were similar to those re- ported in phase III studies of anti- TNF agents in which most of the BY PATRICE WENDLING Frontline Medical News From Rheumatology A wearable pulsed electromagnetic fields device reduced pain inten- sity and improved physical func- tioning in patients with painful knee osteoarthritis (OA) in a double-blind, randomised trial. The commercially available device (ActiPatch, Bioelectronics Corp.) did not improve patients’ mental health, but significantly reduced patients’ intake of NSAIDs and analgesics, compared with placebo. “Although NSAIDs remain the gold standard for the treatment of pain in OA, there is increasing need to find conservative and alternative ap- proaches, in order to avoid the toxicity associated with the chronic use of the analgesics, mostly in the elderly popu- lation,” wrote Dr Gian Luca Bagnato of the University of Messina (Italy) and his colleagues. Pulsed electromagnetic fields (PEMF) therapy has been shown to reduce chondrocyte apoptosis and MMP-13 expression of knee cartilage and favourably affect cartilage ho- meostasis in animal models, but data regarding osteoarthritis (OA) pain and function in humans are mixed. A recent systematic review found no effect in all 14 trials analysed, but when only high-quality randomised clinical trials were included, PEMF

Courtesy BioElectronics Corporation

27.12 MHz, a pulse rate of 1,000 Hz, and a burst width of 100 microsec. Persistent pain was defined as a minimal mean score of 40 mm for global pain on the VAS (visual analog scale) and daily pain during the month prior to enrollment despite maximal tolerated doses of conventional medi- cal therapy, including acetaminophen and/or an NSAID. The patients’ mean age was 67.7 years and mean OA dura- tion 12 years. The primary efficacy endpoint was reduction in pain intensity at 1 month on the VAS and WOMAC (Western Ontario and McMaster Universities Arthritis Index). The mean WOMAC total score at baseline was 132.9. At 1 month, VAS pain scores were

provided significantly better pain relief at 4 and 8 weeks and better function at 8 weeks than did placebo ( Rheumatol- ogy 2013;52:815–24). Not only has the quality of trials var- ied, so has the PEMF pulse frequency and duration used in trials, “further limiting the possibility of comparing efficacy and safety,” Dr Bagnato and associates observed. The current study evenly ran- domised 60 patients with radiologic evidence of knee OA and persistent pain to wear the PEMF or a placebo device for a minimum of 12 hours, mainly at night, with the device kept in place with a wrap. The active device emits a form of non-ionising electro- magnetic radiation at a frequency of

Secukinumab cut ankylosing spondylitis symptoms in MEASURE trials

Secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed.

150 mg and 75 mg and for placebo, respectively, (P < 0.001 for both comparisons with placebo). In MEASURE 2, 219 patients re- ceived subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the place- bo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P < 0.001 for the 150-mg dose and P = 0.10 for the 75-mg dose). The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75- mg dose in MEASURE 1 may have been due to the greater exposure at

patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote. “Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added. In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for sub- cutaneous secukinumab at doses of