Rheumatology News

R heumatology N ews • Vol. 4 • No. 1 • 2016 10 LUPUS/CONNECTIVE TISSUE DISEASES

First US clinical practice guidelines arise for Sjögren’s syndrome management

VEBs predict sudden cardiac death in systemic sclerosis I n systemic sclerosis, more than 1190 ventricular ectopic beats per 24 hours of Holter monitoring was 100% sensitive and 83% specific for sudden cardiac death or defibrillator implantation within a year in a prospective cohort study from the Catholic University of the Sacred Heart in Rome. Twenty-four hour Holter monitoring needs to be “part of the routine evaluation in SSc [systemic scle- rosis] with suspicious cardiac involvement” so that patients get implantable cardioverter defibrillators (ICDs) in time, said investigator Dr Giacomo De Luca, a rheumatologist at the university. Arrhythmias secondary to myocardial fibrosis are killers in SSc and sometimes strike patients with mild heart symptoms such as dyspnoea that are eas- ily mistaken for lung involvement, and patients who fall outside of traditional ICD indications such as ejection fractions below 35%. Because of that, “bet- ter risk stratification is desperately needed” to catch patients early “and prevent sudden cardiac death [SCD],” Dr De Luca said at the annual meeting of the American College of Rheumatology. Holter monitoring isn’t a part of routine SSc workup, but Dr De Luca and his team think it might solve the arrhythmia problem. Ventricular ectopic beats (VEBs) over 1,190 per 24 hours have an “excellent positive predictive value. [They are a] warning biomarker of major arrhythmias,” he said. The conclusions come from 100 SSc patients with new-onset cardiac symptoms, generally palpitations and mild dyspnoea, but also some with chest pain or heart failure signs. The subjects wore Holter monitors for 24 hours and then were followed for a mean of 2 years. At baseline, 56 patients had Holter abnormalities. VEBs were the most common, present in 24 patients at a “strikingly high” mean of 2046/24 hours. The number of VEBs correlated with cardiac troponin T (cTnT) levels and inversely correlated with left ventricular ejection fractions. The team also found 19 patients with supraventricu- lar ectopic beats, 14 with episodes of supraventricular paroxysmal tachycardia, and 11 with runs of nonsus- tained ventricular tachycardia, but those problems didn’t prove to be predictors of SCD. During follow-up, seven patients met the study’s combined primary endpoint of SCD or ICD implan- tation. Five died and two had implants at a mean of 8.5 months. The age range was 32–77 years, and me- dian baseline ejection fraction was 40%, but ejection fractions ranged widely and were normal in some, indicating that they don’t reliably predict SCD in SSc patients. None of the seven subjects had pulmonary arterial hypertension; it was ruled out by right heart catheterisation. Compared with the overall cohort, the seven pa- tients who met the primary endpoint had lower ejec- tion fractions and higher numbers of VEBs – all were above 1,000/24 hours at baseline – plus higher levels of cTnT and NT-proBNP [N-terminal prohormone brain natriuretic peptide]. The 1,190 VEBs/day cutoff emerged on a receiver op- erating characteristic (ROC) analysis that proved robust (AUROC = 0.94, P < 0.0001); cTnT above 0.014 ng/ mL and right bundle branch block were independent predictors of VEBs above the cutoff, but prolonged baseline QT intervals had no prognostic value. BY M. ALEXANDER OTTO Frontline Medical News At the American College of Rheumatology annual meeting, San Francisco

address what the experts considered to be the most pressing problems. The foundation launched the efforts after fielding calls from patients reporting that doctors didn’t understand the disease; didn’t take it seriously; or said there was noth- ing that could be done. On the flip side, physicians were calling in about problem patients. “So about 5 years ago, we launched an ini- tiative to address the issues.” With current options, “to tell patients that they don’t need treatment or that nothing can be done is, in my view as a rheumatologist, malpractice,” said presenting author Dr Frederick Vivino, chief of rheumatology at Penn Presbyterian Medical Centre, a University of Pennsyl- vania teaching hospital in Philadelphia. He is also director of the Penn Sjögren’s Syndrome Centre. Rituximab isn’t approved for Sjögren’s, but “clinicians are using it quite frequently be- cause it’s really the only [biologic] out there” for the disease. “We’ve seen moderate im- provement” of organ involvement, vasculitis, neuropathy, and other extraglandular prob- lems, but “it hasn’t knocked our socks off. We need something better than rituximab” for the sickest patients, Ms Hammitt said at the options. Azathioprine is a good option for recalcitrant musculoskeletal pain, as well as organ involvement. have found a workable middle ground – weight-based dosing up to a maximum of 400 mg/day, which is considered safe in a lean person of about 136 pounds. Three months after being prescribed hy- droxychloroquine, however, just 56% of the patients were at a therapeutic level of 500 ng/ mL or more. The rest were either subthera- peutic at 15–500 ng/mL or had no detectable hydroxychloroquine in their blood. The problemwas adherence. “We were hor- rified” at “how poorly compliant patients were in a cohort that is very well educated about the benefits of medication, and surprised by how few of themwere taking their pills as pre- scribed,” Dr Durcan said at the annual meet- ing of theAmericanCollege of Rheumatology. Even so, it’s well known that drug adher- ence is a problem with chronic disease, so “I think our numbers would be similar in any lupus cohort,” she said. The researchers fixed the problem by insisting patients activate their Hopkins electronic health record portal, so they could check their blood work. If their numbers were low, they saw a reminder on their results page to take their pills every day, and the record system added a note to their chart to bring up adherence during the next office visit. The guidelines recommend hydroxychloroquine as the first step for inflammatory musculoskeletal pain, followed, as needed, by methotrexate, steroids, and other

annual meeting of the American College of Rheumatology. The guidelines recommend hydroxychloroquine as the first step for in- flammatory musculoskeletal pain, followed, as needed, by methotrexate, steroids, and other options. Azathioprine is a good option for recalcitrant musculoskeletal pain, as well as organ involvement. Meanwhile, aerobic exercise is important to help with fatigue. A baseline corneal exam is “the most im- portant recommendation” for eye patients, Dr Vivino said. A stepwise treatment algorithm based on the nature and severity of the problem comes next, and can included tear sup- plementation and stabilisation; control of inflammation of the lacrimal glands and ocular surface; systemic therapy with secre- tagogues; tear preservation measures; and eyelid surgery. Salivary deficiency causes cavities in Sjögren’s. “If the patient has dry mouth, they need to be given topical fluoride. Either encourage them to ask their dentist, or, as I would do, just prescribe it, and they should use it on a regular basis. The group also felt that giving medications to stimulate saliva flow,” like pilocarpine or cevimeline, “would likely help prevent caries, as well,” Dr Vivino said. Sugar-free lozenges or chewing gum can also help with saliva flow. The group gave a weak recommendation for chlorhexidine varnishes, gels, and rinses, and a moderate one for nonfluoride remineralising agents. The work was supported by the Sjögren’s Syn- drome Foundation, with no pharmaceutical industry funding. Some of the authors have financial ties to numerous pharmaceutical companies. That’s all it took for most patients. By about their third office visit, 80% of patients were in the therapeutic range. “If you have a measurable outcome, you can significantly impact patient adherence,” Dr Durcan said. There was a trend towards higher disease activity with lower drug levels. The 13% of patients with undetectable levels at their first hydroxychloroquine checkup had a mean Systemic Lupus Erythematosus Dis- ease Activity Index (SLEDAI) score of 2.92, and the 31% who were subtherapeutic had a mean SLEDAI of 2.36. The 56% of patients in the therapeutic range had a mean SLE- DAI of 2.20 (P = 0.04 for trend). Those differences probably didn’t mean much clinically, but “it’s important to note that the impacts of therapy go beyond the immediate impact on disease activity,” Dr Durcan said. Over 90% of the subjects were women, and most were over 30 years old. The few men in the study were a bit more likely to have therapeutic levels of hydroxychloro- quine 3 months after it was prescribed. Hopkins uses in-house mass spectrometry to measure hydroxychloroquine concentra- tions in whole blood, believing it is more accurate and meaningful than the serum levels used elsewhere. The investigators have no relevant disclosures. The work was funded by the US National Institutes of Health.

BY M. ALEXANDER OTTO Frontline Medical News At the American College of Rheumatology annual meeting, San Francisco R ituximab is, for now, the first-line option for Sjögren’s syndrome patients with systemic symptoms severe enough to require biologic therapy, according to new systemic treatment guidelines from the Sjögren’s Syndrome Foundation. In general, tumour necrosis factor in- hibitors are out because of the risk of lym- phoma; Sjögren’s patients are already at risk for the disease. The foundation has also released guidelines for the management of dry eyes and preven- tion of cavities in Sjögren’s. Thirteen more guidelines are in the works to tackle neuro- logic complications, lung disease, lymphoma, and other issues. The ocular guidelines have been published; the systemic and cavity ones will be soon. “We are really excited about this. These are the first US clinical practice guidelines for Sjögren’s. It will be a game changer,” said Katherine Hammitt, the Sjögren’s Syndrome Foundation’s vice president of medical and scientific affairs. Topical fluoride should be used in all patients with dry mouth to prevent cavi- ties, along with measures or medications to increase saliva. A comprehensive corneal exam is the first step for dry eyes to deter- mine if they’re due to a lack of tears or ab- normal oil secretion by eyelid glands, which causes tears to evaporate too soon. Treat- ment proceeds according to the findings. The recommendations are based on a literature review and the consensus of about 100 Sjögren’s experts. The guidelines BY M. ALEXANDER OTTO Frontline Medical News At the American College of Rheumatology annual meeting, San Francisco H ydroxychloroquine dosing based on actual body weight – instead of ideal weight – is appropriate for patients with systemic lupus erythematosus (SLE), according to a review of 686 lupus patients at Johns Hopkins University in Baltimore. Most were dosed by actual weight, 6.5 mg/kg up to a maximum of 400 mg/day. Pa- tients with renal insufficiency were dosed at 200 mg daily, and those on haemodialysis received 200 mg after their sessions. In their analysis, Hopkins researchers calculated that ideal and actual body weight dosing yielded statistically equivalent hy- droxychloroquine blood levels. “This was re- assuring. The take-home message is dosing based on actual weight” – up to 400 mg/day – “is appropriate,” said lead investigator Dr Laura Durcan, now a rheumatology fellow at the University of Washington in Seattle. Rheumatologists generally opt for weight- based dosing, but ophthalmologists prefer to use ideal body weight to prevent overdoses in obese patients at an increased risk for retinopathy. The Hopkins team seems to

Actual-weight hydroxychloroquine dosing works in SLE, up to a point

The investigators had no disclosures.