15 December 2017 The RheumNow Week In Review Save

It's the 12/15/2017. This is the RoomNow Weekend Review. I'm Jack Cush, executive editor of roomnow.com, here to review the news from the past week on roomnow.com. Welcome to all of you who are listening in on podcasts, exercising, driving in the car, falling asleep even. You can view these podcasts on the website or on YouTube.

You can sign up for the podcasts on both YouTube and subscribe on YouTube on iTunes and also on SoundCloud you can subscribe. At the top of the news, interesting news about tocilizumab and giant cell arteritis. Sort of a big news from the last few meetings, one of the major advances in therapy, finally a drug that's not a steroid that can be given to elderly people that will significantly alter the outcomes of large vessel vasculitis, in this case giant cell arteritis, certainly a big splash and it's been approved for use in The United States. It's been looked at in other jurisdictions and just today it was announced by NICE and the National Health Service in The UK that they were not going to approve tocilizumab for use in giant cell arteritis. And that's after an extensive analysis basically showing that it doesn't make financial sense.

Citing cost concerns and not enough qualities of a benefit from this sort of therapy, there will not be an approval at least in the immediate future. We'll see how this plays out in other countries. A new biosimilar has been approved by the FDA. In fact, the FDA has been sort of active with a number of things again this week. And this is yet another infliximab biosimilar.

This one belongs to Pfizer, who as you do know, is currently well, bought out Horizon and is currently marketing Inflectra. They now have this new one called Inixifi, I x I f I, and it's infliximab q b t x as the suffix that identifies it. This now becomes the third infliximab or Remicade biosimilar on the market in addition to the originator product, the other two biosimilars being Inflectra and Renflexis, and then it is now the sixth TNF inhibitor to be approved by the FDA since April 2016. The other drugs that have been approved include Arelzip, which is the butanercept biosimilar, Amgovita and adalimumab biosimilar, and siltelzotilso from Boehringer Ingelheim, the other atalizumab biosimilar. Again, a lot of biosimilars now on the market, yet where's all this biosimilar action and all this biosimilar savings?

Sort of we're waiting for this to happen. We're waiting to see how it's gonna play out and then I guess there's gonna be some legislative issues. The question is how are switching go? In my hospital, they changed over to Inflectra and dropped infliximab without telling, Remicade without telling me. And my patients didn't know they were getting Inflectra, the new Remicade biosimilar, and it's been happening for the last almost a year.

And they're doing that at a 10% savings. A gigantic mistake if you ask me. They should be holding out for a better deal. So how will switching go? When will it occur?

Will it be under your control or not? These are again very challenging issues. And again I think the problem is will we be comfortable with this? Will we be recommending this? What I've learned from managed care is that they want to see this happen but they don't want it to be where it's like maybe in this case and maybe not in that case.

This only works for managed care when the rule is everybody gets the biosimilar and nobody gets the originator product. When that happens, biosimilars will take hold, there will be savings, and everyone's supposed to be happy from the insurer to even the PBMs, the pharmacy benefit managers, the patients and the doctors. Now, I see that stage being a long ways off. This is gonna be an interesting year or two coming up with biosimilars. I tweeted this week a report on the use of FDG PET scanning to diagnose patients who have either fever of unknown origin or inflammation of unknown origin.

And it's a two forty patient study and this got a lot of hits, a lot of retweets, lot of comments. And the bottom line is that in these two forty patients with either IUO or FUO, the addition of PET scanning was able to increase the diagnostic yield such that one hundred and ninety of these two forty patients could be diagnosed with the scanning, that's seventy nine point two percent. Most common diagnoses made by PET scanning included Still's disease amongst the FUO patients. Now I don't know why, there's nothing specific about Still's disease on FUO, but other than to say they don't have cancer, that might have been the diagnostic yield. In IUO patients, large vessel vasculitis, PMR, and IgG4 related disease were the most common diagnosed conditions.

Each of these is about fifteen, twenty to twenty percent of the overall diagnoses made. When looking at where the utility was greatest, it seemed to be in those patients with either FUO or IUO were over the age of 50 years old who had a CRP of greater than three point o milligrams per deciliter or thirty milligrams per liter and had no evidence of fever. So, again, it's an expensive test. It certainly has a lot of utility in the cancer world and in several other conditions, but maybe it has a role here in these often difficult to diagnose cases. A small pilot study looked at the utility dermatomyositis and polymyositis patients who are refractory to therapy and may be treating them with abatacept.

So it's a small pilot trial, 20 patients with either PM or DM, and they either get abatacept right off the bat initially or there's a three month delay in the initiation of abatacept. So when you look at patients at three months time, fifty percent of the patients who received abatacept were better by their primary endpoint that was used. And then when everybody got abatacept and they looked at it at six months later, eight out of nineteen, or again, fifty percent of patients were achieved the primary endpoint suggesting a response. Again, a small study, it's very limited, the numbers are hard to extrapolate to large populations, but it is encouraging that these 20 patients who are otherwise refractory to steroids and azathioprine and other like therapies did respond with the addition of avatarsin. As you know, TNF inhibitors don't work very well here.

The rituximab trials failed in myositis, but that could be a lot of different issues there. And a lot of rheumatologists do use rituximab even though it's not approved and it failed. Here's another option. It'll be interesting to see if the company pursues this as a therapeutic indication. Other avatacept information comes from the ASH meeting.

The American Society of Hematology had a report at its meeting where patients were being treated with avatacept for the prevention of graft versus host disease, GVHD, that would accompany stem cell transplants in patients who are getting either for cancer or blood disorders, where again GVHD can be a real big problem after the fact. Herefore we have a lot of therapies being used, none of them being very successful, but in this case when Avitasip was used, the GVHD rate went down from thirty two percent to two percent. That's encouraging data. Another interesting report looks at the monitoring of patients with lupus and specifically looking at the complement activation product C4D as a marker for activity of lupus. Turns out that all patients who had lupus and who were quiescent had normal C4D levels.

On the other hand, as patients got more sicker and sicker, C4D levels correlated very well with disease activity and had a positive predictive value for disease activity of almost seventy percent. It correlates with high sleep eye levels, especially as activity goes up, not surprising. And it also is shown that patients who have a high C4D and high double stranded DNA titers have a fivefold higher risk of nephritis. So again, it's not something that we commonly use or is it commonly available, but it should be another useful way of looking at lupus. I'd like to see more studies like this.

A report came from the Scandinavian literature looking at Finnish patients who are DMAR naive with early RA, seventy plus percent are rheumatoid factor positive, and shows what happens when they get treated either with conventional DMARDs or triple therapy. While there was an advantage for triple therapy over conventional therapy, I think the important thing is that almost seventy five percent of early RA patients achieved a dash 28 dash three remission at three months and six months respectively. So by six months, three quarters of patients are in remission. The dash twenty eight three is the joint count I'm sorry, ten minute joint count, swollen joint count, and the CRP and drops the patient global. Now while the dash twenty eight three is not felt to be as useful or as, sensitive as the dash twenty eight, four, which is this dash twenty eight CRP that includes the CRP and the patient global, is still a cheap and easy way of looking at things and finding these kind of remission rates, is really impressive and basically says that if you could get patients with early disease and you treat them aggressively, very high rates of response will be seen.

This is not necessarily surprising, but most of us think we achieve disease remission in a vast majority of our patients. And in the past, the numbers weren't very good. Data taken from real world registries show that initiation of DMARDs or combinations or biologics really only have about a thirty, forty, maybe fifty percent LDAS rate and that remission rates are even lower. But yet we seem to think we do better, and here's the data that says you can do better, but the limiting factor here is getting patients with early disease. The bottom line is you should promote who it is that you wanna see and when you wanna see them, that you'll see more patients instead of just waiting for patients to come to you.

These early RR patients are out there and they're not gonna survive your three week or three month wait list. They need to have a fast easy conduit. A very interesting report was published this week regarding Felty syndrome and its similarities with large granular lymphocyte leukemia, LGL leukemia. Recent reports have shown that LGL leukemias have an association between some STAT3 and STAT5 mutations that may be integral into the pathogenesis of this disease. Given some of the similarities between Sjogren's and LGL leukemia, these investigators sought to do the same analyses.

They looked at 14, only 14, but tell me this last time you saw a FELTYS patient, fourteen patients with FELTYS and did the same analysis. What they found was that forty three percent of FELTYS patients had this STAT3 mutation. It's found in the SH2 domain of STAT3, which is felt to be a sort of hotspot mutations. And it is the same spot and the same mutation that is seen in patients with LGL leukemia where again the rate there is thirty to forty percent. So the numbers are about the same, the mutation seems to be the same.

Again, these patients not only have the same mutation, but they also have the same expansion of CD8 positive T cells and the same cytokine profiles as did the LGL leukemia patients. This may be a very important advance in our understanding of Sjogren's syndrome, which is I think a very hard condition to actually understand the pathogenesis of. Other reports looked at febuxostat in early RA. The interesting thing about this particular study was that it's an early RA sorry. It's an early gout study, and who gets the early gout?

Early gout in this study was defined as patients who had either one or two prior attacks and no more, And they were randomized to receive placebo or febuxostat at forty milligrams. And if they did not achieve an SUA, uric acid of less than six within fourteen days, they were then escalated to eighty milligrams, and many of them actually did that. The interesting thing about this particular study, early gout, where have you seen that? Two, they looked at x-ray and imaging outcomes, kinda unusual. While they showed that there was clinical benefit, patients obviously on had a significant lowering of their serum uric acid levels.

And they looked at flare rates and patients on febuxostat had lower flare rates between six months and two years. In the first six months, everybody had flare rates, it was a mess. But they looked at imaging outcomes and surprisingly, looking at plain x rays, there was no reduction in erosions, even though the disease was better controlled with fluxostat. However, when they looked at the RamRisk scoring system of MRIs, saw a reduction in synovitis in patients who are on febuxostat. Again, a very interesting phenomenon.

Some of the problems here. One, this kind of study has never been done. Two, dropout rates were higher, around forty percent or more. And a lot of that has to do with men and men with gout and they're just unreliable, they don't come back and they're nomadic. They're really hard to do these kind of studies.

It may be that x-ray changes in gout are not like that seen in RA because the disease can be episodic and it may take longer to establish this kind of radiographic change. So while it's encouraging that we saw a synovitis change, maybe a little discouraging that there's not yet a radiographic change. I'd like to know what would happen if the therapeutic intervention was instead of fulbuxostat another xanthine oxidase inhibitor allopurinol. Or what would happen when you use peglodecase? Will Will that actually retard the erosions?

We need to see these kind of studies going forward. The big news from the FDA this week was the approval of meplizumab. This is closely called Nucala. This drug is actually approved for use and has been approved, I think, since 2015 for use in severe asthma with a heavy eosinophilic component. It is now approved largely on the basis of the New England Journal report that appeared earlier this year that showed that patients who have, Church Strauss disease or EGPA who are given mepolizumab every four weeks have a significant, higher rate of of remission.

I include a b a BVAS of zero, you know, little or no steroids, etcetera. And while half the patients didn't respond to this therapy, the response rates were about fifty percent for those that were on mebolizumab and basically zero to five percent for those that were on placebo. So this is a nice addition for a very difficult to treat disease. Lastly, offspring of women, who have rheumatoid arthritis, what happens to their kids in the long run? Not after birth, but what about their development and do they develop other diseases?

This is actually a really big issue with the FDA and people who wanna study outcomes in pregnancy, especially with regard to chronic disease and the use of drugs. So I've always advocated and my review literature says, it's not the drugs that cause the problems, it's disease activity in the mother that causes the problems, which is why you need to treat RA or lupus aggressively during pregnancy so that they can have the best possible outcome for the mother and the child. So the data that they looked at here is very large numbers. And I think this is a Scandinavian study with very large numbers. And basically what they showed is that women who have RA, their offspring is at have a higher risk of developing three things, chronic diseases.

Number one is thyroid disease in children with an odds ratio of two point two, I think. Childhood epilepsy, increased odds ratio of one point six. And rheumatoid arthritis. The increased odds of developing rheumatoid arthritis in the offspring is two point nine million, a threefold increase in the odd. This is a little bit shocking if you ask me and it'll be interesting to see if this could be repeated in other locales.

But this is important data, this again speaks to the fact that we need to do better at controlling disease activity to have better outcomes for the mother and the child. What they didn't do in the study is they did not look at the drugs that were used in the mothers. Again, this is mostly in an era where biologics weren't available and the traditional therapies might have been. So again, more study is needed in this area. That's it for this week at RheumNow the and week in review.

Go to the website and you can look up these links and learn more about what's happening in rheumatology. We'll see you next week.