Tuesday, 21 May 2019

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2018 Rheumatology Year In Review

This annual appraisal of hallmark moments, news and research articles from 2018 are gleaned from that published in RheumNow during the last year and filtered by other news sources and literature review.  The top 10 list herein is rooted in what rheumatologists should know and what will likely change their standards and practice in the future, if not 2019. 

  1. New Drugs. It seems like every year the FDA again sets a record in drug approvals and this year tops their history with 59 newly approved drugs.  The drugs affecting rheumatology and inflammatory diseases include baricitinib (Olumiant) for RA, fostamatinib (Tavalisse) for chronic ITP, and tildrakizumab (Ilumya) for moderate-to-severe plaque psoriasis. While many of the other new agents qualify as orphan drugs, the FDA has been scrutinized by the Government Accountability Office for the proliferation of new orphan drug approvals; felt by some as being abused and allowing either a shortcut to market or an unneeded pathway to expand the market with an already approved drug. https://buff.ly/2R3sEUp
  2. Immune related Adverse Events (irAEs) with Immune Checkpoint Inhibitors. The growth of new highly effective, checkpoint inhibitor agents for use in malignancy has given rise to a new syndrome of immune-related adverse events (irAE) that include a wide spectrum of autoimmune inflammatory musculoskeletal syndromes.  Although uncommon, patients presenting with irAEs have been seen by nearly half of US rheumatologists.  Moreover it appears that irAEs are even more common in patients with pre-existing autoimmune disease. https://t.co/aNHIE86B8r   https://buff.ly/2F3hAzr
  3. Erelzi v. Enbrel Goes to Court.  There are currently 6 FDA approved biosimilars in the US market – 3 infliximab biosimilars (Inflectra, Renflexis, Cyltezo, and Ixifi), 2 adalimumab biosimilars (Amjevita, Cyltezo) and one etanercept biosimilar – Erelzi.  Despite these approvals, biosimilars have yet to change the biologic economics, use or outcomes in rheumatology.  Many of these companies have been involved with legal wrangling’s to extend their exclusivity via patent litigation or patent deals with competitor biosimilars. Sandoz’s Erelzi was FDA approved in 2016, but 2 years later hasn't been launched commercially. Sandoz has been in court with Amgen to challenge Amgen’s patents protecting Enbrel until 2029. A decision by the New Jersey district court on these patent issues is expected in (early?) 2019.  https://buff.ly/2xguFQu  
  4. Opioid Overdose Crisis. The tragedy continues to stay at the top of this annual list, this year for the 4th year in a row. The numbers underlying this are truly tragic. As such pain management will become more scrutinized, regulated and possibly require mandatory education.  More importantly, a few, deserved pain patients are being victimized by the stain and fear of narcotic use. 
    • The USA has the highest per capita rate of opioid use in the world.
    • U.S. drug overdose deaths exceeded 72,000 or ~ 200 deaths per day; lead by heroin, fentanyl, other opioids, methamphetamine and cocaine. https://t.co/jfayrQbt5d
    • Gabapentin is the 10th most prescribed drug in USA; 22% of opioid abusers abuse this drug and in some states it accounts for a high number (4-41%) of overdose deaths. https://t.co/UVOB9Kif6S.
  5. You Don’t Know JAK.  Despite being on the market since 2012, the janus kinase (JAK) inhibitor tofacitinib's growth and uptake was slower than expected and took until 2017 to become a blockbuster drug with more than $1 billion sales ($1.35B).  In 2018, the FDA approved the JAK inhibitor baricitinib and it is expected that other JAK inhibitors (upadacitinib, filgotinib) will soon follow. The tide of orally administered new “JAKinibs” is beginning to swell, while the whole class of TNF inhibitors is under attack from non-TNF biologics (abatacept, rituximab, tocilizumab) and new TNF inhibitor biosimilars. Will JAK inhibitor uptake fall in line behind these other options or will they jump ahead in the arsenal based on their efficacy, safety and oral use.  Do you even know how JAK inhibition works? Is this even important?
  6. ACR18 Hot Topic. This award goes to the “SEAM-PsA” study that was presented at the Annual ACR meeting in October. A head-to-head trial designed to answer the question what is best in psoriatic arthritis – methotrexate, etanercept or both (MTX +  ETN). After 24 weeks of therapy, there were several surprises to this 851 patient trial: a) MTX did far better than I expected, posting a 51% ACR20 response; nonetheless, ETN monotherapy (61%) and combination MTX + ETN (66%) were significantly better at week 24;  b) ETN monotherapy was significantly better than MTX monotherapy for Minimal Disease Activity (36% vs 23% with MTX); and c) there was no added response if MTX was added to ETN in patients with PsA. https://buff.ly/2CN6exI 
  7. Lupus Trials on Fire.  Also presented at ACR 2018, very encouraging phase 2 trials showing the superiority of ustekinumab (vs placebo) in lupus and another win for baricitinib (vs placebo) in lupus. The type 1 interferon inhibitor, anifrolumab (which looked great in phase 2), failed to achieve its primary endpoint in a large phase 3 trial.  There are numerous other new agents being studied in lupus trials including Tyk2 inhibitors, BTK inhibitors, and voclosporin, among others. https://buff.ly/2UBdcNs 
  8. All That Is Unknown about Medical Marijuana. Rheumatologists are perplexed about medical marijuana and cannabinoid therapy. Even in states where it is not legal or commercialized, expensive CBD oils are propounded to cure patients a drop at a time.  2018 has been a banner year for marijuana legalization in America with medical marijuana approved in 21 states and medical and recreational marijuana approved in another 10 states. In October Canada legalized marijuana, becoming the first country to do so. And Mexico, who recently ruled that marijuana prohibition is unconstitutional, is planning to follow Canada's lead.  While marijuana has become an economic, social and political windfall, it is an evidence-based disaster with essentially no proof of efficacy or reasonable approach to use. The current best practice and advice on cannabis use is likely to come from a guy named “Paco” sporting a Fu Manchu moustache and no scientific training.  Former executives with the FDA have declared that if marijuana applied for a New Drug Application it would fail on nearly every benchmark needed to bring a drug to market. My advice is to hold out for better evidence before you jump on the band wagon Paco is steering. 
  9. Walk of Shame on Expensive Drugs. The price of drugs continues to be a large public health problem. Potentially made worse by the rising costs of doing clinical trials and the rising cost of stardom (Direct-To-Consumer Advertising costs have also increased). Amidst the economic complexities of pharmaceuticals there are several standouts in rheumatology. These include historically cheapie drugs that became fiscal budget breakers by being priced beyond expectations. These agents include penicillamine (Cuprimine) with an annual cost of $31,426 ($261.89/tablet); repriced by Valeant for Wilson’s disease. Also, Acthar (ACTH) once cost $40 a vial in 2001, but now costs more than $40,000 per vial and cost Medicate a half-billion dollars when it paid $16,2371 per patient for nearly 3100 patients (https://t.co/cskPO7OM1E).  Lastly, what happens with you combine a higher dose cheap OTC NSAID with a cheap acid blocker? You get one of those nifty (potentially safer) combination drugs that can cost more than $3000 for a month’s supply (Duexis [ibuprofen/famotidine] costs $3,215/month; Vimovo [naproxen/omeprazole] costs  $3,093/month, according to GoodRx.Com).
  10. Senolytics.  A potentially novel approach to managing arthritis involves senolytics wherein the removal of senescent cells may improve osteoarthritis. This approach has been applied in animal models with aging mice that were given the senolytic coctail of quercetin and dasatinib (a JAK inhibitor) and were found to reduce the number of circulating senescent cells, improve (mice) physical function and overall survival. https://t.co/f0atuq54H0 


The author has received compensation as an advisor or consultant on this subject

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