Osteoporosis remains a concern among rheumatoid arthritis patients


CME NUGGETS

Ed Susman

Mr. Susman is a freelance medical writer based in Florida, USA. He travels worldwide to report from medical conferences, writing regularly for wire services, internet websites, and medical journals such as the Journal of the National Cancer Institute and AIDS.

For comments, edwardsusman@cs.com


The worldwide coronavirus COVID19 pandemic has disrupted events everywhere, and that included medical meetings. But the meetings still go on, virtually at least, such as the European League Against Rheumatism, one of the largest sessions that deals with arthritis and related disorders.

The meeting was supposed to be in Frankfurt, Germany7, but was conducted over the internet, and a number of studies looked at the relationship between rheumatoid arthritis and osteoporosis. In one study, researchers observed that among patients diagnosed with rheumatoid arthritis who also fulfill the criteria for osteoporosis, treatment with denosumab appears to improve or maintain bone mineral density after a year of therapy.

In a consecutive series of 140 patients — 135 of whom were women – there was a 5.9% improvement from baseline in bone mineral density at the lumbar spine (P<0.01); a 4% increase in bone mineral density at the proximal femoral (P<0.01) and a 1.2% improvement in bone mineral density at the femoral neck (P=0.36), reported Shosei Anno, MD, of Osaka Social Medical Center in Japan.

“Denosumab improved bone mineral density in patients with rheumatoid arthritis independently regardless of disease activity, use of biological disease-modifying anti-rheumatic drugs, the concomitant type of vitamin D and pre-treatment of osteoporosis,” Dr. Anno reported in an abstract prepared for the meeting.

In Dr. Anno’s study, patients were evaluated by dual energy X-ray absorptiometry at baseline and one year after treatment.  The 140 patients included 75 patients considered to be in remission or having low disease activity; 65 patients were diagnosed with moderate or high disease activity.

The researchers reported that when the patients were compared by disease activity state, the effect of denosumab remained consistent with the entire cohort. In those with low disease activity there was a 6.4% improvement in lumbar spine bone mineral density compared with a 5.3% improvement among those with active disease (P=0.91); at the proximal femoral, the improvement was 3% among the patients with low disease activity and 5.1% in the group with active disease (P=0.73), and there was a 2% improvement in the  femoral neck among the patients with low disease activity, and 0.3% improvement among those with active disease (P=0.1).

Dr. Anno reported a similar story when looking a treatment with biologics – 45 patients, including 23 on anti-tumor necrosis factor drugs, 13 on who were on tocilizmab; 7 on abatacept and 2 on tofacitinib – when compared with 93 patients who were not being treated with biologics. The pattern persisted also when the patients were stratified by the type of vitamin D – active form or native form of the vitamin; or whether they were pre-treated with bisphosphonate and/or teriparatide, or were not on osteoporosis pre-treatment.

In another study, researchers reported that when teriparatide is administered to combat progression of rheumatoid arthritis, the favorable changes obtained with teriparatide is attenuated by co-administration of biologics and/or glucocorticoids.

But when biologics and glucocorticoids are used together, the difference is dramatic, reported Yuji Hirano, MD, of Toyohashi Municipal Hospital in Japan.

Dr. Hirano and colleagues, in their abstract presentation, said that after 24 months, patients who were receiving teriparatide but were not receiving either biologics or glucocorticoids achieved a 15.5% increase in bone mineral density when measured at the lumbar spine. If the patients were taking teriparatide and biologics, the improvement in bone mineral density at 24 months was 12.7%. If the patients were on teriparatide and glucocorticoids the bone mineral density increased 11.9%. But if the patient was on both biologics and glucocorticoids the improvement was diminished to an 8.1% increase at 24 months. There were no statistically significant differences between the groups, Hirano reported.

However, the pattern was similar when analyzing bone mineral density in the total hip, the researchers reported. The increase with patients only on teriparatide was 6.4% at 24 months compared with an increase of 1.5% among patients on teriparatide as well as biologics and glucocorticoids (P=0.03).

“This study suggested that concomitant use of biologics and glucocorticoids inhibited the increase in bone mineral density induced by teriparatide treatment in patients with rheumatoid arthritis, particularly total hip bone mineral density,” Dr. Hirano reported.

In a third study, researchers found that about 25% of the patients diagnosed with systemic lupus erythematosus – who were on glucocorticoids and were also diagnosed with chronic kidney disease – were not given treatment to combat osteoporosis, even though the osteoporosis is exacerbated by kidney disease and use of glucocorticoids.

“Osteoporosis is one of the most important adverse effects of glucocorticoids in patients with systemic lupus erythematosus,” reported Ken-Ei Sada, MD, of the Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences in Japan. “Because osteoporosis is accelerated by chronic kidney disease, more attention should be paid to the treatment for osteoporosis in lupus patients with chronic kidney disease. Many treatment options for osteoporosis have emerged recently, but treatment status in patients with lupus is not elucidated.”

In their abstract, the research team accessed data from lupus registry of nationwide institutions. The researchers enrolled 917 patients, 88% of them were women. The average age was 44 years. Bisphosphonates were administered to 388 (42%) of patients; vitamin D supplements were given to 448 (49%) patients; Calcium supplements were prescribed to 36 (4%) patients; denosumab was prescribed to 20 (2%) patients and teriparatide was administered to 14 (2%) patients.

Dr. Sada noted that the records indicated that 225 patients or 25% did not received any treatment.

“About a quarter of patients with lupus did not take any treatment for osteoporosis,” Sada reported. “Treatment for osteoporosis might be strengthened to prevent bone damage in lupus patients with chronic kidney disease.”

In a poster presentation that dealt with treatment of gout, John Botson, MD, medical director of Orthopedic Physicians Alaska in Anchorage, reported that in an open-label study of 14 patients experiencing acute gout attacks, 11 patients were able to use a pegloticase/methotrexate combination to reduce uric acid levels to near undetectable levels, and far below the 5 mg/dL level recognized as the threshold for development of crystals that cause the gouty attacks.

Pegloticase has been approved since 2010, Botson said, “but it hasn’t gotten a lot of traction” because its effectiveness is attenuated by development of anti-drug antibodies and infusion reactions. He said his study – to be followed by a larger controlled clinical trial – picks up on case reports that methotrexate might help overcome the problems.

Pegloticase (pegylated uricase) is the only FDA-approved medication for uncontrolled gout, Botson said. When used as monotherapy in the phase 3 trials, 42% of patients were treatment responders to pegloticase, able to reduce uric acid to less than 6.0 mg/dL during treatment months 3 and 6. About 26% of patients had infusion-related reactions.

“As is often done for other rheumatic diseases treated with biologics, some physicians are using

immunomodulation therapy with pegloticase,” he explained. “Recent case series support the use of pegloticase/methotrexate  co-therapy, with reported responder rates of 80%-100%. However, cases had

varying doses, timing, and administration routes.” His study showed an efficacy of 78.6%.

“Pegloticase is an interesting drug,” he said, “because if it works in patients it’s success in lowering uric acid is dramatic. But if it doesn’t work, it has almost no impact, and you know almost immediately.”

In the study, the mean serum uric acid level was 8 mg/dL at baseline, and after 2 weeks of treatment, the level was reduced to a mean of 1 mg/dL. When patients who did not respond to therapy were removed from the study after 12 weeks, the level reached undetectable levels.

The role of pegloticase is to get the serum acid level down, said Dr. Botson. Then the patient can take other medications to keep the level low. He said that patient compliance with maintenance therapy is the main reason gout attacks may recur.

“An increased proportion of patients treated with pegloticase and methotrexate maintained a therapeutic response during Month 6 compared to previously reported rates for pegloticase alone,” he reported. “Results of the current trial are in agreement with two recent case series. No new safety concerns were identified.

“A definitive randomized, double-blinded trial evaluating pegloticase with methotrexate versus pegloticase with placebo is needed to confirm our results and is ongoing (MIRROR RCT),” he said.

In the MIRROR open-label trial, Botson reported, patients undergo a 2-week screening program, followed by a 4-week methotrexate run-in phase in which 15 mg or methotrexate is taken weekly, followed by a 52-week period in which pegloticase 8 mg intravenous every 2 weeks and oral methotrexate 15 mg every week is given to patients.

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