Humira and uveitis

Researchers from the RHAPSODY study, which is examining the efficacy of adalimumab (Humira) on ankylosing spondylitis, report that the incidence of uveitis is markedly reduced among patients receiving the anti-TNF treatment.

Golimumab and ankylosing spondylitis

Golimumab: another TNF-alpha antagonist for us to keep track of (I wonder what the trade name will be). According to a press release, "More than half of patients receiving monthly subcutaneous (SC) injections of golimumab (CNTO 148) 50 mg and 100 mg experienced significant and sustained improvements in the signs and symptoms of active ankylosing spondylitis, according to Phase 3 study results presented at the American College of Rheumatology (ACR) annual meeting."

At some point there will be as many biologics at our disposal as there currently are NSAIDs. Not that they'll be as cheap.

Researchers implicate two genes in development of AS

In what is being called a major genetic breakthrough, researchers have identified a relationship between two genes and the development of ankylosing spondylitis. Their research was published in Nature: Genetics today. From the media release: "The researchers have identified two genes, ARTS1 and IL23R, which increase the risk of developing the disease. Together with the genetic variant HLA-B27, this takes the number of genes definitely known to be involved in the disease to three. A person carrying all three variants would be expected to have a one in four chance of developing the disease."

But wait, there's more. The IL23R gene has already been implicated in Crohn's disease, which we already knew was closely related to AS. From the media release again, quoting Queensland University professor Matthew Brown: "'We already know that IL23R is involved in inflammation, but no one had ever thought it was involved in ankylosing spondylitis,' says Professor Brown. 'A treatment for Crohn's disease that inhibits the activity of this gene is already undergoing human trials. This looks very promising as a potential treatment for ankylosing spondylitis.'" So already there are therapeutic implications: interesting.

TNF antagonists and skin cancer

According to a study published in Arthritis and Rheumatism (abstract), TNF therapy is associated with an increased risk of skin cancer. The study examined 13,001 rheumatoid arthritis patients in clinical trials and compared their cancer rates with the general public. Via About.com Arthritis.

Newcastle AS study

A Newcastle University researcher is carrying out a study on young people with ankylosing spondylitis; "[p]atients with ankylosing spondylitis (AS) who attend the Freeman and North Tyneside Hospitals in Newcastle, Queen Elizabeth Hospital in Gateshead, and Wansbeck Hospital in Ashington will be asked to participate." The story is vague about the parameters of the study, but it appears that education is at least one focus.

It's in the family

We've known for a while that ankylosing spondylitis and its related illnesses tend to run in families. In my case, my grandfather -- who turns 91 next month -- had AS as well, and an uncle had Crohn's disease. A recent study turned to Iceland -- and its small, homogenous population and extensive genealogical database -- to quantify the risk of contracting AS or inflammatory bowel disease if a close relative has it as well.

First-, second-, and third-degree relatives of patients with AS had risk ratios of 94, 25, and 3.5, respectively, indicating an increased risk of developing AS, while first-, second-, and third-degree relatives of patients with IBD had risk ratios for IBD of 4.4, 2.2, and 1.4, respectively. In addition to confirming the genetic risk for AS and IBD independently, the study found elevated cross-risk ratios between IBD and AS in both first- and second-degree relatives. The cross-risk ratios for IBD in first- and second-degree relatives of patients with AS were 3.0 and 2.1, respectively, and, notably, were the very same for AS in first- and second-degree relatives of patients with IBD. Overwhelmingly, findings applied to blood relatives.

Results of two-year clinical trial reported

During a two-year clinical trial, the results of which were announced today, ankylosing spondylitis patients taking Remicade (infliximab) "experienced significant improvement in spinal mobility ... [and] showed sustained reductions in spinal inflammation through two years as detected by magnetic resonance imaging." The ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial involved 279 patients, 78 of whom received a placebo. I'm assuming this is a company-sponsored study.

Inflammatory rheumatic disease and aortic inflammation

Another thing to worry about: a new study suggests that inflammatory rheumatic diseases like ankylosing spondylitis are a predictor of aortic inflammation.

Gender differences in ankylosing spondylitis

Via About.com Arthritis, a clinical study examining the influence of gender on the severity of ankylosing spondylitis. The study looked at 302 men and 100 women who had AS for more than 20 years. The women had an earlier onset of disease, were more likely to have a first-degree family member with the disease, and had more peripheral symptoms. But the study also observed the following:

1. Radiographic spinal damage was worse among men.
2. Functional disability was the same among men and women.
3. After adjusting for radiographic spinal damage, women reported worse functioning.

I'm having trouble understanding what that means -- and it's probably beyond the scope of any medical study to infer general conclusions from such data. But these data suggest to me a discrepancy: either the disease is worse in women for a given level of spinal damage (although, on average, the men were in worse shape -- median scores of 10 vs. 6.5 -- just that a woman with 6.5 would report worse functioning than a man with 6.5), in some as-yet unquantifiable way, or women are overreporting/men are underreporting their symptoms.

Something subtler, I hope, than "women bitch more about pain," but I recall a study a few years back -- I'm too tired to look for a link at the moment -- that said that if men and women reported the same amount of pain, the men got more medication for it, on the assumption that women were more likely to complain and men were more likely to suck it up. Now, I'm male and a big wuss and I complain all the time, so I'm leery of stereotypes and would hate to see them confirmed, but you know ... how do you explain worse self-reported functioning for the same observed data?

Omega-3 fatty acids and ankylosing spondylitis

We've all been told, I think, about the anti-inflammatory benefits of omega-3 fatty acids, but now there's a clinical study about their efficacy against ankylosing spondylitis (see also). It turns out that while relatively low doses of omega-3 accomplished little, disease activity was reduced among those taking high doses. (High and low doses mean 4.55 g and 1.95 g per day, respectively. The omega-3 doses came from marine sources; I wonder if it matters.)

Anti-TNF treatments and ankylosis

Anti-TNF therapy has been shown to do a good job reducing inflammation, but joint inflammation is only one aspect of our disease. What about ankylosis -- joint fusion? A recent study using tests on lab mice suggests that anti-TNF treatments aren't as effective:

Their findings [...] cast doubts on the feasibility of preventing joint and spine ankylosis with anti-TNF strategies while shedding light on the process of SpA. [...]

For the mice with induced arthritis, etanercept had a significant impact on disease severity, inhibiting inflammation and cartilage and bone destruction. For the mice with spontaneous arthritis, however, etanercept proved no more effective than placebo at inhibiting new cartilage or bone formation or ankylosis. [...]

"Our observations strengthen our hypothesis that new bone formation in SpA is clinically relevant and largely independent of inflammation," Dr. Luyten states. "Long-term results from clinical trials are required to corroborate this hypothesis in patients with SpA," he acknowledges, "and to define whether the process of ankylosis should become a separate therapeutic target."

Metalloproteinase 3

Medical News Today: "The protein marker, metalloproteinase 3, now identified as the first significant predictor of joint damage in ankylosing spondylitis, could change patient treatment approaches, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC."

Update, 11/15: More on the protein marker from MedPage Today: the implication is that metalloproteinase 3 can predict just how severe the disease is going to be in an individual case, and indicate whether aggressive and expensive treatments (Enbrel, Humira, Remicade) are necessary, or not. Not all of us are facing the same level of severity, after all, but we can't predict how bad it's going to get at the outset.