Subcutaneous methotrexate can be given at higher doses than in the oral route and still maintain its bioavailability, which could make it easier for patients to tolerate the drug and for clinicians to better adhere to treatment guidelines, a pharmacokinetic study suggested.
In other recent rheumatology news, three of four patients with clinical amyopathic dermatomyositis survived a bout of rapidly progressing interstitial pneumonia following treatment with a monoclonal antibody that targets the interleukin (IL)-2 receptor, and chronic arthritis doesn't appear to be a feature of Lyme disease in Norwegian patients.
Subcutaneous Methotrexate Beats Oral
The use of subcutaneously administered methotrexate may help overcome some of the difficulties associated with oral administration of the drug such as inadequate bioavailability with high doses, a head-to-head study suggested.
Pharmacokinetic evaluations determined that, with oral methotrexate, the mean plasma concentration, as measured by the area under the curve (AUC) for 24 hours, reached a plateau at the 15 mg dose, while subcutaneous administration was associated with consistent "dose-proportional" concentrations, according to Michael H. Schiff, MD, of the University of Colorado in Denver, and colleagues.
The bioavailability of methotrexate is inconsistent because of problems with gastrointestinal absorption, and typically decreases with high doses. In addition, many patients experience gastrointestinal side effects following oral administration -- yet the drug remains the cornerstone of therapy for rheumatoid arthritis and is recommended as first-line treatment in international guidelines.
"Doses greater than 15 mg/week are frequently used to control disease activity, but may be only partially effective in some patients and poorly tolerated by others," Schiff and colleagues wrote online in Annals of the Rheumatic Diseases.
The FDA recently approved a self-injection device for methotrexate (Otrexup) for use by adults with active rheumatoid arthritis or psoriasis and for children with active polyarticular juvenile idiopathic arthritis.
To assess the bioavailability of the drug delivered by this device, the researchers conducted a crossover study that included 47 adult patients with rheumatoid arthritis who were taking 10, 15, 20, or 25 mg of methotrexate per week.
Patients each were given their current dose in three ways: as a single oral dose, as a subcutaneous injection in the abdomen, and as a subcutaneous dose in the thigh.
Compared with the oral drug, the ratio of dose-normalized AUC over 24 hours for the subcutaneous formulation was 127.61 (95% CI 122.30-133.15), while the maximum observed concentration for each dose was 94.88 (95% CI 87.95-102.37), the researchers reported.
In addition, the bioavailability of the subcutaneous drug compared with the oral drug increased with higher doses:
10 mg, 121%
15 mg, 114%
20 mg, 131%
25 mg, 141%
Findings were similar for the subcutaneous treatment in the abdomen and thigh, according to the researchers.
The treatment was "generally safe and well tolerated," with no unexpected safety events.
"The current study is the first to compare bioavailability across commonly prescribed doses of oral and subcutaneous methotrexate and raises the possibility that there is no advantage to increasing the oral methotrexate dose above 15 mg/week, a common clinical practice," Schiff and colleagues wrote.
Antibody Saves Lung in Dermatomyositis
Three of four patients with clinical amyopathic dermatomyositis survived rapidly progressive interstitial pneumonia when treated with the monoclonal antibody basiliximab, which is used for the prevention of organ rejection following transplant, Chinese researchers reported.
Amyopathic dermatomyositis is related to the autoimmune conditions dermatomyositis and polymyositis, but is characterized primarily by skin rashes without muscle involvement. Interstitial lung disease is a common complication and usually has been treated with high-dose corticosteroids and immunosuppressive agents, but treatment has often failed.
Increases in the soluble interleukin-2 receptor (CD25) have been identified in patients with autoimmune diseases such as systemic sclerosis, and a recent open-label study found benefits for basiliximab among patients with progressive systemic sclerosis.
Because activated lymphocytes are involved in the pathogenesis of dermatomyositis, and the soluble IL-2 receptor appears to correlate with disease activity, Chunde Bao, MD, and colleagues from Shanghai Jiao Tong University tried using the CD25 blocker basiliximab in their series of patients.
The four patients, whose average age was about 52, developed progressive disease, with dyspnea, respiratory failure, and bilateral infiltrates seen on high resolution CT.
Scores on high resolution CT ranged from 110.8 to 185.8, with the highest score being in the patient who died.
Other clinical findings included heliotrope rashes and Gottron's papules in all patients.
They were receiving prednisone and cyclosporin A, and when the ratio of partial pressure arterial oxygen and fraction of inspired oxygen fell below 300, two infusions of 20 mg basiliximab were given each week.
One patient died after the first infusion, but in the other three patients, high resolution CT scores decreased by 26% to 45% and serum ferritin levels fell, the researchers reported in a letter in Annals of the Rheumatic Diseases.
The authors noted that the treatment with prednisone and cyclosporin A before the basiliximab infusions may have contributed to the positive outcomes, but recommended that a larger clinical trial be undertaken to further evaluate this approach.
Lyme Arthritis in Norway
Chronicity and persistence don't appear to be characteristic of Lyme arthritis in an area of Norway endemic for Lyme borreliosis, researchers reported in BMC Infectious Diseases.
In the coastal areas of Southern Norway, Ixodes ricinus ticks are common, and Borrelia burgdorferi is present in about one-quarter of the ticks.
One in five adults in the area have IgG antibodies against B. burgdorferi, according to Glenn Haugebert, MD, of the Hospital of Southern Norway Trust in Kristiansand, and colleagues.
Previous work in Norway has found neuroborreliosis to be the most common disease manifestation, developing in 71% of patients. Arthritis has been reported to occur in 22% and acrodermatitis chronica atrophicans in 5%.
Between January 2007 and December 2010, a total of 27 patients with suspected Lyme arthritis were evaluated in the local hospital. Patients' mean age was 56, and the mean duration of symptoms was 11.2 weeks.
Definite Lyme arthritis was confirmed in 16 on the basis of serologic findings; probable Lyme arthritis in five, who were serologically positive but other causes couldn't be completely ruled out; and no Lyme arthritis was found in six, who turned out to have conditions such as osteoarthritis and rheumatoid arthritis.
Among patients with definite or probable Lyme arthritis, mean erythrocyte sedimentation rate was 31 mm/hour and mean C-reactive protein level was 43 mg/dL. All had high titers of serum IgG antibodies to B. burgdorferi, and IgM antibodies also were present in eight.
A total of 19 of the definite or probable cases were treated with doxycycline for 2 to 8 weeks. No flares occurred following antibiotic treatment in 11, a single transient flare was seen in three patients, and two flares in two others.
During mean follow-up of 54 weeks, none of the patients developed chronic or recurrent arthritis. However, reports in the literature have suggested that some 10% of patients experience chronic arthritis, and "there are major controversies whether there is a chronic form of Lyme disease and if there is a subgroup of patients who require long-term antibiotic treatment beyond 1 to 2 months."
"All attempts to illuminate this possibility have not revealed any objective evidence of such a hypothesized link between an ongoing active infection with B. burgdorferi and chronic clinical signs and symptoms," the researchers observed.
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