Final Results and Thank You

What an amazing All Star Season. In the end, Cortisone cut down the nets as the most important and transformational article ever written in the field of rheumatology.

To see how your bracket did, head over to the RheumMadness Tourneytopia website.

Below is a detailed analysis of the entire tournament.  We’d also like to highlight all the amazing people who collaborated to make this tournament the best one yet – see below.

Final Match-up: Cortisone defeats Etanercept for RA (4-3)

This was almost a huge upset – Cortisone barely beat Etanercept for RA in a 4-3 nail-biter according to Blue Ribbon Panel (BRP) votes. Here is what the BRP had to say about this year’s winner:

  • “A championship for the ages! Both teams made spectacular, innovative plays (ie new mechanisms of action), took care of the ball (patient care) hit their free throws down the stretch (persistently effective). But cortisone has touched more lives across a broader array of diseases for a longer time, so it cuts down the nets for me.”
  • “Nobel Prize aside…it was cortisone that changed all our thinking in rheumatology. Every drug developed since cortisone was an effort to mimic its benefits and minimize the cortisone toxicity.”
  • “Etanercept led the way for biologics, but let’s not forgot who started it all. The fact that so many of our current efforts are targeted toward minimizing steroids just highlights their importance in our field. A flashy Noble prize doesn’t hurt as well.”
  • “While everyone in rheumatology has a love / hate relationship with glucocorticoids, no other discovery has advanced therapeutics in our field to a greater degree.”

Despite Cortisone being the heavy favorite, Etanercept for RA made it close. Here is what the BRP had to say in favor of Etanercept for RA:

  • “It goes without saying that this final was a very difficult matchup. There’s no doubt regarding the force that ‘cortisone’ has brought to the rheumatology world, and we all knew from the beginning it was a favorite in the tournament as it has been in previous years. However, every one loves an underdog story, and perhaps ‘Etanercept for RA’ was the one needed to dethrone ‘cortisone’.Etanercept for RA’ changed the treatment landscape for RA, very much triggering the biologic renaissance in rheumatology. No easy task, and to make such a revolutionary impact demands the respect it rightfully deserves.”
  • “TNF inhibitors ushered in the era of durable responses for patients with RA, with e a remarkable safety profile. Rheumatology has never been the same.”

Did they get it right? Here’s a breakdown of all participant picks for the winner of RheumMadness 2023: The All Star Season. Basically, once you made it past cortisone, it was anyone’s game!

Team Name Votes (N) %
Cortisone 56 39%
Abs before SLE 13 9%
RAVE 12 8%
TICORA 9 6%
Etanercept for RA 8 6%
LUMINA 7 5%
TEAR Triple Rx 5 4%
Pathogenic ANAC 4 3%
Clonal Selection 4 3%
HCQ Withdrawal 3 2%
Infliximab for RA 3 2%
MSU & NLRP3 3 2%
HAQ 3 2%
Etanercept + MTX 2 1%
CCP & Enolase 2 1%
ALMS Trial 2 1%
CYC for PAN 2 1%
ULT During Flare 2 1%
BeSt 1 1%
Origin of RA 1 1%
Origin of sJIA 0 0%
CYC in Scleroderma 0 0%

Participant Winners

This year, we received 142 bracket submissions from participants in 13 different countries. Here’s a breakdown of who submitted a bracket for RheumMadness 2023:

  • Attending: 44%
  • Fellow: 26%
  • Resident: 13%
  • Medical Student: 5%
  • APP: 3%
  • Patient/interested citizen: 3%
  • Other health care professional: 1%
  • Chose not to answer: 5%

Prizes are awarded for participants who submitted a bracket in three categories: 1) Attending / APP, (2) Fellow, and (3) Resident / Medical Student. Members of the RheumMadness Leadership team are not eligible to receive these prizes. This year, the prizes go to:

  • Attending / APP: RobShmerling (41 points, link shows their bracket)
  • Fellow: lveder8 (40 points, link shows their bracket)
  • Resident / Medical Student: Gmaldonado (39 points, link shows their bracket)

Thank you so much to everyone who played!

Time to Say Thank You

This was our biggest season ever, which means we have so many people to thank. First, thank you to the Rheumatology Research Foundation for supporting this project with the Clinician Scholar Educator (CSE) Award.

We would also like to thank the leaders of NephMadness for allowing us to borrow their amazing educational model to create RheumMadness.

Thanks to the Scouting Report Authors

The real all stars of RheumMadness are the scouting report authors who create reviews of each team in the tournament. This year, the scouting reports were written by 123 collaborators from 19 fellowship programs and 2 private practice groups, including 76 fellows, 40 faculty, 4 residents, and 3 medical students. What an amazing collaboration! Thank you to all those who wrote the scouting reports for each team, as follows:

  • Etanercept for RA, by the Ohio State Fellowship Program
  • Etanercept + MTX, by the University of Chicago Fellowship Program
  • Infliximab for RA, but the University of California San Diego Fellowship Program
  • TEAR Triple Rx, by the UT Southwestern Fellowship Program
  • BeSt Trial, by the Medical University of South Carolina Fellowship Program
  • TICORA Trial, by the Arthritis & Rheumatism Associates Practice, Washington DC
  • Clonal Selection, by the Vanderbilt University Medical Center Fellowship Program
  • MSU & NLRP3, by the Geisinger Medical Center Fellowship Program
  • Abs before SLE, by the Massachusetts General Hospital Fellowship Program
  • CCP & Enolase, by the University of South Florida Fellowship Program
  • Pathogenic ANCA, by the University of North Carolina Fellowship Program
  • CYC for PAN, by the Allegheny Health Network Fellowship Program
  • CYC in Scleroderma, by the Louisiana State University Shreveport Fellowship
  • ULT During Flare, by the Medical College of Wisconsin Fellowship Program
  • RAVE Trial, by the Wake Forest Fellowship Program
  • HCQ Withdrawal, by Bryn Mawr Medical Specialists Association Practice
  • ALMS Trial, by the University of Alabama and Birmingham Fellowship Program
  • LUMINA, by the Northwestern University Fellowship Program
  • HAQ, by the RheumMadness Leadership Team
  • Cortisone, by the University of Colorado Fellowship Program
  • Origin of RA, by the Duke University Fellowship Program
  • Origin of sJIA, by the Montefiore Pediatric Fellowship Program

Thanks to The Rheumatologist

Thank you to the editorial staff of The Rheumatologist for their amazing support of RheumMadness over the last 3 years, including this article highlighting the 2023 tournament:

RheumMadness 2023: the All-Star Season

Thanks to theMednet.Org

We would also like to thank theMednet.org for collaborating with us to create even more content for this year’s RheumMadness tournament. theMednet.org is a physician only site providing a space for physicians to tackle difficult clinical questions and see how colleagues are practicing. theMednet is featuring select Q&A relevant to articles in our 2023 tournament, providing a space for further discussion and polling around clinical application. They offer free CME and MOC credit for reviewing this material. Register here for a free account with full access to the theMednet site. After registering, click here to find RheumMadness content on theMednet, with Q&A about the following topics:

  1. How do you approach follow up of young patients with isolated +ANA, but no current clinical signs or symptoms of SLE?
  2. Do you use IL-1 inhibitors to prevent flares of gout or CPPD in patients who experience flares despite prophylaxis with colchicine, NSAIDs, and/or low-dose prednisone?
  3. Do you ever consider discontinuing hydroxychloroquine in patients with SLE in longstanding remission except in cases of overt toxicity?
  4. Are there certain patients in whom you would avoid initiation of ULT during an acute gout flare?
  5. Do you use conventional DMARDs aside from methotrexate to prevent anti-drug antibody development for patients on infliximab?
  6. Is there a role for monitoring serum ANCAs to assess ANCA associated vasculitis disease activity?

Thanks to the 2023 Blue Ribbon Panel

Next, we’d like to thank our amazing Blue Ribbon Panel (BRP). This panel worked hard to review each article and scouting report, and they didn’t mind taking the heat for all those upsets in the early rounds. Thank you so much to our panelists!

Thanks to the 2023 RheumMadness Leadership Team

Finally, we’d like to thank all the members of the RheumMadness Leadership Team for the 2023 tournament.

Finally, thank YOU for playing.  We can’t wait to do this again next year!

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Round 4 Results

The IgG4 (fourth round) of RheumMadness is complete!

To see how your bracket is doing, head over to the RheumMadness Tourneytopia website.

Results for reach matchup in the second round are reviewed below, including how the  Blue Ribbon Panel (BRP) voted compared to participant picks.

Match-up 1: Etanercept for RA defeats Abs Before SLE (6-1)

The winner of the TNF Takedown didn’t need any Ab workouts to move on to the next round, with Etanercept for RA defeating Abs Before SLE in a 6-1 blowout per the BRP.

Here’s what the BRP had to say in support of Etanercept for RA:

  • “Etanercept for RA punches its ticket to the Championship game by transforming the lives of so many patients, and making Rheumatology so rewarding to practice.”
  • “Etanercept for RA paved way for age of biologic therapy in rheumatology. Abs before SLE provides important clues about SLE pathogenesis but hasn’t led to major breakthrough about disease causality that has led to direct therapeutic advancement.”

The lone supporter of Abs Before SLE said this: “Seminal study that defines the beauty of autoantibodies.”

Participants were much more split than the BRP, though Etanercept for RA did receive the most participant picks to win this round.  Here’s the breakdown of which team participants thought would win this round:

  • Etanercept for RA: 20%
  • Abs Before SLE: 18%
  • TICORA: 15%
  • TEAR Triple Rx: 10%
  • Infliximab for RA: 9%
  • Etanercept + MTX: 8%
  • Pathogenic ANCA: 6%
  • MSU & NLRP3: 5%
  • BeSt: 4%
  • Clonal Selection: 4%
  • CCP & Enolase: 1%

Match-up 2: Cortisone defeats RAVE (7-0)

Cortisone continues behaving just the way it does in the immune system: defeating everything. It won this round in a blowout, defeating RAVE 7-0. Here’s what the BRP had to say about this match-up:

  • “Cortisone started it all. We hate and love them (note that I mention hate first), but who says an All-Star can’t be polarizing?”
  • “Cortisone’s all-star duo of transforming treatment and clarifying the biochemical mechanism of RA were too much for even the impressive RAVE squad.”
  • “RAVE was a great study but it’s applicable only to a small subset of patients within the field. Cortisone is for everyone.”
  • “The OG med.”

Did they get it right? The VAST majority of participants picked cortisone as well.  Here’s the breakdown of participant picks for this round:

  • Cortisone: 51%
  • RAVE: 17%
  • LUMINA: 8%
  • HAQ: 6%
  • ULT During Flare: 5%
  • HCQ Withdrawal: 4%
  • ALMS Trial: 4%
  • CYC in Scleroderma: 2%
  • Origin of RA: 2%
  • Origin of sJIA: 1%
  • CYC for PAN: 1%

What’s next?

We will release the results of the Interleukin-2 (the championship) on Monday, April 3.

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Round 3 Results

The Entheseal 8 (third round) of RheumMadness is complete!  After a tournament full of upsets, this round seemed to go smoothly for the favorites. To see how your bracket is doing, head over to the RheumMadness Tourneytopia website.

Results for reach matchup in the second round are reviewed below, including how the  Blue Ribbon Panel (BRP) voted compared to participant picks.

Match-up 1: Etanercept for RA defeats TICORA (5-1)

TICORA missed the target in this one, losing to Etanercept for RA in a 5-1 vote from the BRP. Here’s why the panel picked Etanercept for RA:

  • “Introduction of successful biologic therapy into RA with just gorgeous dose response curves was groundbreaking. T2T strategy of TICORA is nice but was already also being studied in other concurrent trials in RA like the BEST trial.”
  • “Etanercept was the original quantum shift in ‘modern’ era rheumatology.”

Did the panel get it right? YES. According to participant picks, the BRP nailed this one. Here’s a breakdown of all participant picks for the winner of this round:

  • Etanercept for RA: 25%
  • TICORA: 20%
  • TEAR Triple Rx: 20%
  • Etanercept + MTX: 13%
  • Infliximab for RA: 12%
  • BeSt: 8%

Match-up 2: Abs Before SLE defeats Clonal Selection (5-2)

Abs Before SLE pulled out the win in this match-up, defeating Clonal Selection 5-2 in BRP votes. Here’s why:

  • “Both studies are giving us lots of clues about pathophysiology that we still have yet to decipher. But Abs before SLE provides more practical information to fuel discovery and perhaps at the moment more relevant to rheumatology – or at least at the moment is a more famous paper in rheumatology.”
  • “Coach Burnet of Forbidden Clones wrote the transformational playbook about antibody formation that was later exploited by Coach Arbuckle’s Abs Before SLE team. So Abs should advance.”

The majority of participants also picked Abs Before SLE in this match-up.  Here’s a breakdown of all participant picks for the winner of this round:

  • Abs Before SLE: 46%
  • MSU & NLRP3: 20%
  • Clonal Selection: 15%
  • Pathogenic ANCA: 11%
  • CCP & Enolase: 8%

Match-up 3: RAVE defeats CYC for PAN (6-1)

Rituximab tied cyclophosphamide in RAVE, and the BRP felt that was enough for the win in RheumMadness, with RAVE defeating CYC for PAN 6-1. Here’s what they had to say:

  • “RAVE was an elegant trial and finally allowed us to have a less toxic treatment option for ANCA+ disease.”
  • “Cyclophosphamide is on the decline in rheumatology, and for AAV rituximab is increasingly standard of care thanks to this trial. Both trials impressively conducted with very little preliminary data to support efficacy.”

In contrast, the lone supporter of CYC for PAN said this: “RAVE and CYC for PAN were equally important for patients, but the Fauci/Wolff study was just more transformational and groundbreaking.”

What did participants think? The overwhelming majority picked RAVE.  Here’s a full breakdown of participant picks for this match-up:

  • RAVE: 46%
  • HCQ Withdrawal: 18%
  • ALMS Trial: 11%
  • ULT During Flare: 11%
  • CYC for PAN: 8%
  • CYC in Scleroderma: 6%

Match-up 4: Cortisone defeats HAQ (6-1)

Cortisone entered the tournament as a heavy favorite, and it continued its dominant run in this matchup, defeating HAQ 6-1. Here’s what the BRP had to say:

  • “Research papers come in all shapes and sizes, but not too many lead to Nobel prizes.”
  • “The granddaddy”. Can’t imagine a rheum without steroids in their back pocket!!

In contrast, the lone supporter of HAQ said this: “You can’t play the game today without both cortisone and PROs like HAQ. But only one will survive well into the future. Clinicians and clinical researchers will always need the HAQ. It may bust brackets, but HAQ gets my vote.”

The majority of participants also picked cortisone to win this round. Here’s a full rundown of participant picks:

  • Cortisone: 65%
  • LUMINA: 17%
  • HAQ: 11%
  • Origin of RA: 6%
  • Origin of sJIA: 1%

What’s up next?

Results for the next 2 rounds will be released on the following dates:

  • Round 4: Saturday, April 1 (the IgG Four)
  • Round 5: Monday, April 3 (the Interleukin Two, aka the championship!)
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Round 2 Results

The second round of RheumMadness was full of upsets and a few surprising blowouts. To see how your bracket is doing, head over to the RheumMadness Tourneytopia website.

Results for reach matchup in the second round are reviewed below, including how the  Blue Ribbon Panel (BRP) voted compared to participant picks. Huge thanks to our amazing panel for their thoughtful consideration.

Subscribe to our newsletter to stay updated with all things RheumMadness!

 

Match-up 1: Etanercept for RA defeats Infliximab for RA (5-2)

This was the match-up everyone wanted to see. Infliximab was the first anti-TNF molecule ever studied for RA, and etanercept was the first anti-TNF agent approved by the FDA for the treatment of RA. In the end, etanercept took the win 5 to 2.

In support of Etanercept for RA, the BRP said, “TNFi vs TNFi. Both seminal studies but ETN shot to popularity in use due to convenience.”

In contrast, a BRP member who voted for infliximab had this to say: “The transformational aspect as first human biologic TNF but also showing disease modification which was critical.”

Did they get it right? According to participant picks, 39% picked Etanercept for RA and 37% picked Infliximab for RA (the remainder picked Etanercept + MTX which lost in Round 1). So in the end, most participants agreed with the panel, but JUST BARELY!

Match-up 2: TICORA defeats TEAR Triple Rx (5-1)

This was, at least according to participants, another huge upset. According to the Blue Ribbon Panel (BRP), TICORA had no trouble defeating TEAR Triple Rx, even with Dr. Worthing abstaining from the vote again. TEAR Triple Rx only mustered one vote.

BRP comments in support of TICORA: “T2T was the game changer that changed how we approached all future studies.”

However, participants did NOT agree, with 43% of all participant brackets picking TEAR Triple Rx in this round versus 35% who supported TICORA. The remaining 22% picked BeSt, which lost in round 1.

So who got it right? The panel or the participants? Use #RheumMadness to tell us what you think.

Match-up 3: Clonal Selection destroys MSU & NLRP3 (7-0)

Wow. This was another huge upset. According to the BRP, the mechanism madness region was a blowout, with Clonal Selection receiving every single BRP vote. Here’s what the BRP had to say:

  • “This team has some of the best fundamentals of the whole tournament. Well earned Nobel for a doctor Burnet. But the inflammasome was critical.”
  • “Fundamental theoretical paper.”

Yet again, the majority of participants did NOT agree, with only 44% picking Clonal Selection and 56% picking MSU & NLRP3!

We are sure no one will have any strong opinions about this on social media 🙂

Match-up 4: Abs Before SLE defeats Pathogenic ANCA (7-0)

Another blowout, this time in the Ab workout region, with Abs Before SLE receiving all 7 BRP votes. Sounds like myeloperoxidase, considered by some to be the Most Villainous Protein (MVP) of the tournament, didn’t come ready to play this round.  Here’s what the BRP had to say:

  • “Both scouting reports are stuffed full of outstanding hoops references and transformational, novel data. But Abs Before SLE pulled away down the stretch by influencing the care of millions more people with preclinical positive test results.”
  • “Higher conceptual impact in rheumatology.”
  • “The concept of antibody formation leading to disease led to the search for other “pathogenic” antibodies in other diseases.”

This time, participants agreed, with 67% picking Abs Before SLE versus just 16% picking Pathogenic ANCA. Interestingly, those who chose CCP & Enolase remained faithful to their team, with 17% picking it to win the entire region. Oh well, nice try!

Match-up 5: CYC for PAN defeats ULT During Flare (5-2)

Now this was an interesting upset. CYC for PAN defeated ULT During Flare in BRP votes, 5-2, however the majority of participants disagreed.

Here’s why the BRP chose CYC for PAN:

  • “John Stuart Mill and the utilitarian philosophers step into the arena with this classic test of saving the lives of a few vs improving the lives of many. CYC for PAN wins in double overtime when Coach Fauci dramatically leaves a man under the hoop to cherry pick 17 times while ULT sticks with its deliberate, controlled study all game.”
  • “Use of cyclophosphamide has greater impact across many diseases in rheumatology.”

In contrast, one member of the BRP who voted for ULT During Flare said this: “If there is one thing we continually have to teach and reteach non rheumatologists, it is this.”

The majority of participants disagreed with the BRP, with 46% picking ULT During Flare, and just 25% picking CYC for PAN. The remaining 29% picked CYC for Scleroderma, suggesting their fanbase is more loyal than CYC for PAN.

Match-up 6: RAVE defeats ALMS Trial (6-1)

The Jump Ball region was certainly not a toss-up. RAVE dominated the ALMS Trial in BRP votes, 6-1.

Comments from the panel in support of RAVE: “RAVE more strongly disrupted standard of care, and the scouting report was just too good for RAVE.”

In contrast, the lone BRP who voted for ALMS had this to say: “Best matchup yet! RAVE may have one of the best names in the tourney, but it I think it loses in a squeaker to ALMS, who showed up to practice and ultimately gave patients an oral option for life-changing treatment,”

The majority of participants agreed with the BRP, with 61% picking RAVE to win this region. Interestingly, only 14% of participants picked the ALMS Trial to win this region, compared with 25% of participants who stayed true to HCQ Withdrawal despite its early exit in round 1. The bottom line? Rheumatologists sure love their rituximab and hydroxychloroquine!

Match-up 7: HAQ defeats LUMINA (5-2)

Another region, another upset, this time in The Whole Patient Region. Here, the BRP picked HAQ over LUMINA, 5-2. Comments from the panel in support of HAQ:

  • “Foundational for patient reported outcomes.”
  • “Post-game interview said it all. 40 years hence, every one of my patients completes a HAQ. Teams in other regions are trembling — except RA Revamp!”

Participants disagreed, with 54% picking LUMINA and 46% picking HAQ. To us, it sounds like everyone is passionate about caring for The Whole Patient, with strong support for both teams!

Match-up 8: Cortisone defeats Origin of RA (5-2)

Finally, in the Origin Story region, Cortisone defeated Origin of RA 5-2, and the vast majority of participants agreed.  The main surprise of this region was that cortisone didn’t all 7 votes!

According to the BRP in support of cortisone:

  • “Cortisone wins this rare, heartbreaking (because early) matchup of two powerhouses. We now know that cortisone would be effective for both primary asthenic gout and ordinary gout even if Dr. Landré-Beauvais hadn’t distinguished the two.”
  • “The mainstay of our treatment paradigms and the story of its discovery is amazing. Talk about a shift in how rheumatology was approached!”
  • “Glucocorticoids are the currency of rheumatology.”

The overwhelming majority of participants agreed, with 86% picking Cortisone, 11% picking Origin of RA, and 3% remaining true to Origin of sJIA.

What’s up next?

Results for the next 3 rounds will be released on the following dates:

  • Round 3: Tuesday, March 28 (the Entheseal Eight)
  • Round 4: Saturday, April 1 (the IgG Four)
  • Round 5: Monday, April 3 (the Interleukin Two, aka the championship!)

Round 1 Results

The first round of the RheumMadness tournament is complete!  We received 142 bracket submissions from participants in 13 countries – the most we’ve ever had.

To see how your bracket is doing, head over to the RheumMadness Tourneytopia website.

Results for reach matchup in the first round are reviewed below, including how the  Blue Ribbon Panel (BRP) voted compared to participant picks. Huge thanks to our amazing panel for their thoughtful consideration.

Overall, the first round was incredibly close – 4 of the 6 match-ups were decided by a single vote!  In fact, we had to pull in an extra Blue Ribbon Panel member to break a tie for BeSt vs. TICORA.

Match-up 1: Etanercept for RA (4) defeats Etanercept + MTX (3)

This was a real nail-biter! In the end, Etanercept for RA won in a 4-3 vote. This team will move on to face Infliximab for RA in the next round.

Comments from BRP members who voted in favor of Etanercept for RA:

  • “First in human is a big deal”
  • “First out of the gate study on TNFi…game changer at the time”
  • “Presenting the first biologic drug in RA – quite transformational!”

In contrast, a BRP member who voted in favor of Etanercept + MTX said, “This trial was pivotal to the FDA’s approval of etanercept in MTX non-responders.”

Did they get it right?  According to participant brackets, 59% picked Etanercept for RA and 41% picked Etanercept + MTX.

Match-up 2: TICORA (4) defeats BeSt (3)

This was the closest match-up we’ve ever had. Because Dr. Worthing’s group wrote the scouting report for TICORA, he had to abstain from this vote.  Chaos ensued, as the rest of the BRP members were split, 3-3.  To settle the score, we called in an alternate BRP member, Dr. Donald Thomas (creator of The Lupus Encyclopedia, @lupuscyclopedia) to break the tie.  Ultimately, in the words of Dr. Thomas, “TICORA out Bested BeST.”  WOW what a matchup. TICORA will now move on to face TEAR Triple Rx in the next round.

One BRP member who voted in favor of TICORA said this: “Both are relevant concepts (early treatment and radiographic outcomes vs T2T) behind our current practice. Still, the proof of T2T is an important concept that has expanded beyond RA and is relevant to our current approach to treatment.”

In contrast, we have two comments from BRP members who voted for BeSt, as follows:

  • “Reversing the old RA “pyramid” treatment paradigm, this study showed that early aggressive treatment, whether with conventional or biologic DMARDS, leads to better outcomes.”
  • “BeSt revolutionized clinical trial design in rheumatology.”

Did they get it right?  According to participant brackets, 54% picked TICORA and 46% picked BeSt.

Match-up 3: Pathogenic ANCA (4) defeats CCP & Enolase (3)

Pathogenic ANCA won this one in another 4-3 vote and will move on to face Abs Before SLE in the next round.

Two BRP members had this to say in support of Pathogenic ANCA:

  • “An elegant animal model that demonstrated that ANCA is more than just a biomarker.”
  • “Pathogenic ANCA more definitively established causality.”

In contrast, a BRP member who voted in favor of CCP & Enolase said this: “Tantalizing to provide a possible reason for our patients condition, and could promise prevention or cure to so many with RA — even if that ball is still rolling around the rim!”

Did they get it right?  According to participant brackets, 61% picked Pathogenic ANCA and 39% picked CCP & Enolase.

Match-up 4: CYC for PAN (5) defeats CYC in Scleroderma (2)

CYC for PAN pulled away late in a 5-2 victory over CYC in Scleroderma. Dr. Fauci’s Favorites will move on to face ULT During Flare in the next round.

The BRP said this in favor of CYC for PAN:

  • “This study was a game changer in the management of PAN.”
  • “Not just a game changer but a life-saver for patients.”
  • “Despite having fewer players, CYC for PAN broke the ground for cyclophosphamide to be used by later teams like CYC in Scleroderma. And the remission efficacy may win the #RheumMadness 2023 Slam Dunk contest!”

In contrast, one BRP member said this in favor of CYC for Scleroderma: “Sorry, Dr Fauci but the Scleroderma lung studies were studied and re studied and subgroup analyzed to death when they game out.”

Did they get it right?  According to participant brackets, only 45% picked CYC for PAN and 55% picked CYC in Scleroderma.  Upset city!

Match-up 5: ALMS Trial (4) defeats HCQ Withdrawal (3)

Oh. My. Goodness. The BRP did NOT choose hydroxychloroquine. They picked ALMS in a 4-3 shocker. ALMS will move on to face RAVE in the next round.

It seems the BRP felt the need to defend their choices as we had more comments about this one than any other match-up.  Those who favored ALMS had this to say:

  • “ALMS transformed the management of lupus nephritis (but this was a very hard pick).”
  • “More ambitious of a trial.”

In contrast, those who picked HCQ Withdrawal said this:

  • “A study I still quote today in daily practice when patients ask if they can stop HCQ. Bit of a no brainer for me.”
  • “Still a pillar in the management of SLE. Great study, always have by your side when “sparring” against ophthalmology LOL.”
  • “HCQ is truly the moneyball of rheumatology! (Even if the A’s didn’t actually win that World Series!)”

Did they get it right?  This one was INCREDIBLY close among participants, with 52% picking ALMS and 48% picking HCQ Withdrawal. What a match-up!

Match-up 6: Origin of RA (6) defeats Origin of sJIA (1)

This was the only blow-out in the first round, with Origin of RA taking the victory 6-1.  To the RheumMadness Leadership team, this means we need more pediatric rheumatology in the tournament next year.  Calling all pediatric rheumatology fellowship programs – please submit teams and write scouting reports so we can have more peds topics!  Origin of RA will move on to face cortisone in the next round.

Here’s what the BRP had to say in favor of Origin of RA:

  • “This was the first recognition that there were different forms of inflammatory arthritis, not just gout.”
  • “Paradigm shifting.”
  • “Landre-Beavais is the James Naismith of rheumatology! Still had more patients, but his paper came out 97 years later, and although JIA’s origin was transformational, fortunately JIA affects many fewer people than RA.”

In contrast, the lone supporter of Origin of sJIA said this: “Kudos to the team for dissecting an article this old! A study that moved the needle from “evil humours.”

Did they get it right?  According to participant brackets, 77% picked Origin of RA and 23% picked Origin of sJIA.

What’s up next?

Results for the next 4 rounds will be released on the following dates:

  • Round 2: Saturday, March 25 (the Seronegative Sixteen)
  • Round 3: Tuesday, March 28 (the Entheseal Eight)
  • Round 4: Saturday, April 1 (the IgG Four)
  • Round 5: Monday, April 3 (the Interleukin Two, aka the championship!)
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The All Star Season is Here

Welcome to RheumMadness – the place for everyone who is crazy about rheumatology to connect, collaborate, compete, and learn together.  RheumMadness is a project funded by a Clinician Scholar Educator Award from the Rheumatology Research Foundation and inspired by a similar project in nephrology called NephMadness.

Our theme for the 2023 tournament is RheumMadness: The All Star Season. This season, we will focus on the foundational science that has driven our field to where it is today. Each of the 22 teams in the tournament will represent one “all star” article competing to be named the most important and transformational article ever written in the field of rheumatology.

How to Play RheumMadness (it’s easy and FREE)

  1. Read “scouting reports” to learn about the teams in the tournament.
  2. Submit your picks before Wednesday, March 22 at 11:59pm ET.
  3. Enjoy! Tournament results will be released in 5 rounds from March 23 – April 3, 2023.

The RheumMadness OnePager

Need a quick review of the teams as you make your picks? We collaborated with Dr. Mithu Maheswaranathan (@MithuRheum), creator of @RheumOnePagers to create an infographic reviewing the entire bracket in one page. Check it out below.

How are matches determined?

The winner of each match-up is decided by a 7-member “Blue Ribbon Panel” of rheumatologists. For the 2023 tournament, the panel will vote based on which topic they think is the most important and transformational article ever written in the field of rheumatology. The more your picks match those of the panel, the more points you get!  For more details about how RheumMadness works, check out our RheumMadness 101 page, which includes a short explainer video and details about our RheumMadness leadership team.

The 2023 Blue Ribbon Panel

We are thankful to have an amazing panel with diverse interests, areas of expertise, and practice settings.

  • Angus B. Worthing, MD, FACP, FACR: Rheumatologist at Arthritis and Rheumatism Associates in Washington, D.C. Follow him at @AngusWorthing
  • Anne R. Bass, MD: Rheumatologist at Hospital for Special Surgery and Professor of Clinical Medicine at Weill Cornell Medicine in New York, New York.
  • Julie J. Paik, MD, MHS: Associate Professor at Johns Hopkins Hospital in Baltimore, Maryland. Follow her at @JuliePaikMD
  • Marie Kuchynski, MD: Senior attending physician, rheumatologist at University Hospitals Cleveland Medical Center; Brunswick Ohio. Follow her at @DoctorKuch
  • Peter C. Grayson, MD, MSc: Rheumatologist and Tenure Track Investigator at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Maryland. Follow him at @petercgrayson
  • Sebastian E. Sattui, MD, MS: Assistant Professor at University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania. Follow him at @SattuiSEMD
  • Daniel E. Gonzalez, MD: Second-year rheumatology fellow at University of Texas Medical Branch in Galveston, Texas.

What do I get if I win?

Participants with the most correct predictions will “win” RheumMadness. Prizes will be given to participants with the top scores in the following categories: (1) Attending / APP, (2) Fellow, and (3) Resident / Medical Student. The prize is a custom RheumMadness coffee mug and a lifetime of bragging rights. But really, everyone wins in RheumMadness because you get to connect, collaborate, compete, and learn together.

 

Ready to start learning about the teams in the tournament? This year, the scouting reports were authored by 123 collaborators from 19 fellowship programs and 2 private practice groups, including 76 fellows, 40 faculty, 4 residents, and 3 medical students. What an amazing collaboration!

  • Etanercept for RA, by the Ohio State Fellowship Program
  • Etanercept + MTX, by the University of Chicago Fellowship Program
  • Infliximab for RA, but the University of California San Diego Fellowship Program
  • TEAR Triple Rx, by the UT Southwestern Fellowship Program
  • BeSt Trial, by the Medical University of South Carolina Fellowship Program
  • TICORA Trial, by the Arthritis & Rheumatism Associates Practice, Washington DC
  • Clonal Selection, by the Vanderbilt University Medical Center Fellowship Program
  • MSU & NLRP3, by the Geisinger Medical Center Fellowship Program
  • Abs before SLE, by the Massachusetts General Hospital Fellowship Program
  • CCP & Enolase, by the University of South Florida Fellowship Program
  • Pathogenic ANCA, by the University of North Carolina Fellowship Program
  • CYC for PAN, by the Allegheny Health Network Fellowship Program
  • CYC in Scleroderma, by the Louisiana State University Shreveport Fellowship
  • ULT During Flare, by the Medical College of Wisconsin Fellowship Program
  • RAVE Trial, by the Wake Forest Fellowship Program
  • HCQ Withdrawal, by Bryn Mawr Medical Specialists Association Practice
  • ALMS Trial, by the University of Alabama and Birmingham Fellowship Program
  • LUMINA, by the Northwestern University Fellowship Program
  • HAQ, by the RheumMadness Leadership Team
  • Cortisone, by the University of Colorado Fellowship Program
  • Origin of RA, by the Duke University Fellowship Program
  • Origin of sJIA, by the Montefiore Pediatric Fellowship Program

 

The RheumMadness team is excited to announce a collaboration with theMednet.org for our 2023 tournament. theMednet is a physician only site providing a space for physicians to tackle difficult clinical questions and see how colleagues are practicing. theMednet will be featuring select Q&A relevant to articles in our 2023 tournament and will provide a space for further discussion and polling around clinical application. Register here for a free account with full access to the theMednet site and find RheumMadness content. Get FREE CME and MOC credit for reviewing this material.

 

  1. Listen to the RheumMadness podcast. In this podcast series, we interview fellows who wrote the scouting reports. You can find the podcast on all major podcasting apps.
  2. Join the conversation on Twitter (#RheumMadness).
  3. Subscribe to our newsletter to stay updated with all things RheumMadness!

2023 Blue Ribbon Panel

We are thrilled to introduce the Blue Ribbon Panel for RheumMadness 2023: The All Star Season.  This panel of distinguished rheumatologists will vote to determine which teams advance in the tournament.  The more your predictions match those of the panel, the more points you will get in the tournament!  Learn more about our panelists below.

  • Angus B. Worthing, MD, FACP, FACR: Rheumatologist at Arthritis and Rheumatism Associates in Washington, D.C. Follow him at @AngusWorthing
  • Anne R. Bass, MD: Rheumatologist at Hospital for Special Surgery and Professor of Clinical Medicine at Weill Cornell Medicine in New York, New York.
  • Julie J. Paik, MD, MHS: Associate Professor at Johns Hopkins Hospital in Baltimore, Maryland. Follow her at @JuliePaikMD
  • Marie Kuchynski, MD: Senior attending physician, rheumatologist at University Hospitals Cleveland Medical Center; Brunswick Ohio. Follow her at @DoctorKuch
  • Peter C. Grayson, MD, MSc: Rheumatologist and Tenure Track Investigator at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Maryland. Follow him at @petercgrayson
  • Sebastian E. Sattui, MD, MS: Assistant Professor at University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania. Follow him at @SattuiSEMD
  • Daniel E. Gonzalez, MD: Second-year rheumatology fellow at University of Texas Medical Branch in Galveston, Texas.
Subscribe to our newsletter to stay updated with all things RheumMadness!

CYC in PAN

Team: CYC in polyarteritis nodosa (PAN), aka “Fauci’s Power Forward”

Region: Get in the Game

Base article: Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med. 1979 Aug 2;301(5):235-8. doi: 10.1056/NEJM197908023010503. PMID: 36563.

Authors: Allegheny Health Network Rheumatology Fellowship. Zaina Shahid, MD, first year rheumatology fellow, Nicholas Wiemer, DO, second year rheumatology fellow, Sara Shahid, MD, first year rheumatology fellow, Michael Lucke, MD, Rheumatology Program Director,

Team Overview

Before 1970, the prognosis of systemic necrotizing vasculitis was abysmal, almost uniformly fatal. Dr. Walton in his survey of 56 patients with systemic vasculitis found the average survival time to be 5 months with 81% of the patients dead within one year of diagnosis.1 The 5-year survival rate of  a cohort of patients from 1946-1962 with a diagnosis termed periarteritis nodosa, the prototypical systemic necrotizing vasculitis, was only 15% in untreated patients. Corticosteroids were the mainstay of treatment improving survival rate to only 48% .2

It was in this grim setting that Drs. Anthony Fauci and Sheldon Wolff reported on 17 patients with severe necrotizing vasculitis studied over the course of 11 years.3 16 of these patients had been treated with corticosteroids for a mean duration of 22 months and had suffered from severe side effects. All 16 patients showed subjective and objective evidence of disease progression despite treatment with corticosteroids. 16 patients were treated with cyclophosphamide 2mg/kg oral per day. 1 patient chose to continue azathioprine. A taper of corticosteroids was initiated within 2 weeks of receiving cyclophosphamide with the goal of discontinuation. 14 patients showed definite remission within 3 weeks of cyclophosphamide therapy. The mean duration of cyclophosphamide induced remission was 22 months with notably no relapses while being on cyclophosphamide. At the end of the study period, remission was achieved in all 17 patients in the study!

Impact on Rheumatology

This dramatic response to cyclophosphamide represented the first important advancement in the management of necrotizing vasculitis. This momentous discovery had significant impact on the lives of patients with systemic vasculitis.  Before this break-through, the average survival time after diagnosis was 5 months.  Now, because of the use of cyclophosphamide and the work done by Drs. Fauci and Wolff, this previously devastating disease has an effective treatment improving the survival rate to almost 80% at 5 years.4 It was a joyous moment for rheumatologists and patients alike.  Cyclophosphamide remained the MVP for many years to come as standard induction treatment of vasculitis.  This legendary player went on to compete against other legends of the game, including rituximab.  However, rituximab has never been able to surpass cyclophosphamide as an offensive player.  Additionally, cyclophosphamide set the stage for innovative treatment in numerous other rheumatic conditions ranging from pulmonary disease in scleroderma, lupus nephritis, and refractory cutaneous and myositis diagnoses.  It also remains a treatment of choice for remission induction in some forms of severe vasculitis .5 This landmark trial continues to impact the field of Rheumatology 50 years since publication.

Chances in the Tournament

A breakout, offensive star like cyclophosphamide is sure to be game changer for this tournament.  A player of this skill hasn’t been seen since Cortisone played back in 1949 for Mayo.  Combined with the skill of Dr. Fauci, a fan favorite known for sinking shots while under immense pressure from the most imposing defenses, this team will be an overwhelming force in the games to come.

Next scouting report: CYC in Scleroderma

Back to the full list of scouting reports.

See the Q&A on theMednet.org for the Get in the Game region: Are there patients in whom you would avoid initiating of ULT during acute gout flare? 

References

  1. Hollander D, Manning RT. The use of alkylating agents in the treatment of Wegener’s granulomatosis. Ann Intern Med. 1967 Aug;67(2):393-8. doi: 10.7326/0003-4819-67-2-393. PMID: 6036397.
  2. Frohnert PP, Sheps SG. Long-term follow-up study of periarteritis nodosa. Am J Med. 1967 Jul;43(1):8-14. doi: 10.1016/0002-9343(67)90144-1. PMID: 4157287.
  3. Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med. 1979 Aug 2;301(5):235-8. doi: 10.1056/NEJM197908023010503. PMID: 36563.
  4. Catherine King, Lorraine Harper, Mark Little, The complications of vasculitis and its treatment, Best Practice & Research Clinical Rheumatology, Volume 32, Issue 1,2018,Pages 125-136,ISSN 1521-6942 https://doi.org/10.1016/j.berh.2018.07.009.
  5. Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Imundo LF, Kim S, Merkel PA, Rhee RL, Seo P, Stone JH, Sule S, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot MA, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatology. 2021 Aug;73(8):1366-1383. doi: 10.1002/art.41773. Epub 2021 Jul 8. PMID: 34235894.

CYC in Scleroderma

Team: CYC in Scleroderma, aka “CYC’d for SLS”

Region: Get in the Game

Base article: Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354(25):2655-2666. PMID 16790698.

Authors: Louisiana State University Shreveport Rheumatology Fellowship. Iman Qaiser, MD, second year rheumatology fellow, Smita Maruvada, MD, second year rheumatology fellow, Jasmeen Uppal, MD, first year rheumatology fellow, Mohammad Hassaan Khan, MD, first year rheumatology fellow, Warda Maqsood, MD, first year rheumatology fellow, Sulman Hasan, MD, second year rheumatology fellow, Kinza Muzaffar, MD, Assistant Professor of Internal Medicine, Madiha Tariq, MD, Program Director Rheumatology, Overton Brooks VA Medical Center Shreveport, Sarwat Umer, MD, Professor of Internal Medicine, Louisiana State University Shreveport, Samina Hayat, MD, Professor of Internal Medicine, Louisiana State University Shreveport.

Team Overview

Scleroderma is a complex, multi-systemic disease. Forty percent of scleroderma patients have pulmonary involvement, mostly interstitial lung disease.1 Ventilatory restriction, along with pulmonary hypertension, is responsible for a staggering mortality rate of 42% within 10 years after disease onset! 2, 3 For a disease that has been such an Achilles heel for rheumatologists since the 1700s, management was still not clearly defined by the millennium and rheumatologists were still playing defense.4 In 2006, Tashkin et al went on offense against scleroderma lung disease and produced this slam-dunk of a study, also known as the Scleroderma Lung Study I or SLS-I, which showed the clear effectiveness of cyclophosphamide in improving and maintaining FVC (forced vital capacity) in scleroderma patients. Between the 158 patients who were randomized, the mean difference in FVC at 12 months between the cyclophosphamide and placebo group was 2.53%, favoring cyclophosphamide with P < 0.03. Not only that, cyclophosphamide also showed significant improvement in TLC (total lung capacity), functional ability, health-related quality of life and skin thickness. The study also clearly demonstrated the downside of cyclophosphamide, with adverse effects of cytopenias. 1

Impact on Rheumatology

While RA, gout and vasculitis got their fair share of glory throughout history, scleroderma was benched far too long. Scleroderma patients, often minority ethnic populations, would die young and suffer effects on every organ system. William Osler wrote in 1898 “On Diffuse Scleroderma”, comparing a scleroderma patient to Tithonus, who wished for eternal life, but forgot to ask for eternal youth: “Like Tithonus to ‘wither slowly’ and like him ‘beaten down and marred and wasted’ until one is literally a mummy, encased in an ever-shrinking, slowly-contracting skin of steel, is a fate not pictured in any tragedy, ancient or modern.” 5 Research into treatment for this cruel disease was long overdue by the 2000s, and the SLS-I team was just what the rheumatology league needed at that point in time.

Haters will say cyclophosphamide was already being used for scleroderma before 2006. True, there were some retrospective studies showing the benefit of cyclophosphamide, but we ask you what degree of confidence would these small studies give you when using a drug known to have high toxicity? 2 The SLS-I study changed the entire game. It was a well-strategized, 2-year long, double-blind, placebo-controlled, randomized, multi-center, prospective study  which drew solid conclusions regarding the efficacy, toxicity and risk-benefit ratio of cyclophosphamide in scleroderma. 1 It gave the rheumatologist that much needed alley-oop to score confidently against scleroderma.

The SLS-I study also laid down a game plan for the SLS-II and SLS-III trials. 6, 7 It was the dream team that all other teams aspired to. It’s clear, this team deserves to be named the most important and transformational article ever written in the field of rheumatology!

Chances in the Tournament

The SLS-I study got in the game when it was needed the most! While vasculitis and scleroderma are both devastating diseases, scleroderma did not get the attention it needed from cyclophosphamide until 27 years later! But when it did, SLS-I owned the court like it was their home! The impregnable strategy with which CYC was studied for scleroderma, makes our team a sure shot winner. Our opponents wouldn’t even be able to defend us man-to-man with their sample size of 17 compared to our 158! 8 Additionally, keeping score might be difficult for them, seeing as they did not use many objective measurements. After that easy win, we would be up against a team that discusses the timing of drug initiation of a drug that has been well studied for decades, in a disease that has been well known for centuries. 9 We question if they should even be in the game when they only made it to a conditional recommendation in the American College of Rheumatology guidelines. 10 Eventually, we would like to be able to jump ball with the RAVE trial, as rituximab is the hot, new player on the block. 11 But let’s see how much steam rituximab can handle when facing off with the MVP, the Michael Jordan, the OG of rheumatology: cyclophosphamide.

Though advances have been made in scleroderma research, there is still a lot that needs to be studied for this overwhelming disease. Our team paved the way forward for future players and researchers in how to deal with this systemic disease in an objective and calculated way, and in the process reach out to the crowds of patients rooting for us. SLS-1 is indeed an all-star in rheumatology!

Next scouting report: ULT During Flare

Back to the full list of scouting reports.

See the Q&A on theMednet.org for the Get in the Game region: Are there patients in whom you would avoid initiating of ULT during acute gout flare? 

References

  1. Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in
  2. scleroderma lung disease. N Engl J Med. 2006;354(25):2655-2666.
  3. Steen VD, Conte C, Owens GR, Medsger TA Jr. Severe restrictive lung disease in systemic sclerosis. Arthritis Rheum. 1994;37(9):1283-1289.
  4. White B, Moore WC, Wigley FM, Xiao HQ, Wise RA. Cyclophosphamide is associated with pulmonary function and survival benefit in patients with scleroderma and alveolitis. Ann Intern Med 2000;132: 947-54.
  5. Adigun R, Goyal A, Hariz A. Systemic Sclerosis. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430875/
  6. OSLER W: On diffuse scleroderma; with special reference to diagnosis and to the use of thyroid extract. Jour. Cutan. & Gen. Urinary Dis., XVI: 49 & 127, (Feb. & Mar.), 1898.
  7. Tashkin DP, Roth MD, Clements PJ, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016;4(9):708-719. doi:10.1016/S2213-2600(16)30152-7
  8. Khanna D, Spino C, Bernstein E, Goldin J, Tashkin D, et al. Combination Therapy of Mycophenolate Mofetil and Pirfenidone vs. Mycophenolate Alone: Results from the Scleroderma Lung Study III. In: ACR Convergence 2022, 10-14 November, 2022, Philadelphia, USA.
  9. Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med. 1979;301(5):235-238.
  10. Taylor TH, Mecchella JN, Larson RJ, Kerin KD, Mackenzie TA. Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. Am J Med. 2012;125(11):1126-1134.e7.
  11. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout [published correction appears in Arthritis Care Res (Hoboken). 2020 Aug;72(8):1187] [published correction appears in Arthritis Care Res (Hoboken). 2021 Mar;73(3):458]. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180
  12. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232.

ULT During Flare

Team: Urate-Lowering Therapy (ULT) During Flare, aka the “Unapologetically Uricase-Deficient Mammals!”

Region: Get in the Game

Base article: Taylor, T. H., Mecchella, J. N., Larson, R. J., Kerin, K. D., & MacKenzie, T. A. (2012). Initiation of Allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. The American journal of medicine, 125(11), 1126-1134. PMID 23098865.

Authors: Medical College of Wisconsin Rheumatology Fellowship Program. Desh Nepal, MD, First-year rheumatology fellow; Rohan Mehta, DO, First-year rheumatology fellow; Yiran Jiang, MD, Second-year rheumatology fellow; Alison Fernandes, MD, Second-year rheumatology fellow; Michael Putman, MD, MSCI, Assistant Professor, Associate Rheumatology Fellowship Program Director

Team Overview

The urate-lowering agent, allopurinol, was discovered in 1956 and approved for mass consumption 10 years later. Allopurinol has remained the treatment of choice for gout management ever since. Yet, before the publication of this double-blind, placebo-controlled randomized control trial [1], it was believed initiation of allopurinol during an acute flare would prolong or exacerbate the attack due to uric acid mobilization [2]. Such practice was based on the observation that after allopurinol initiation, patients had frequent gout flares even as uric acid levels improved [3]. Based on this, rheumatological societies published guidelines recommending benching allopurinol until the flare has subsided [4] [5]. Known as the “delayed initiation and step-up approach,” the pervading thesis was introduced to start allopurinol at a low dose with a gradual increase. Consequently, the patient would only first see allopurinol come into play in low-stakes outpatient follow-up in the office 10-14 days later. Here are a few limitations of this traditional approach that continues to be recommended in the current 2020 ACR guideline [6]:

Delayed initiation equals missed opportunities. Only 64% of post-discharge appointments are generally kept [7]. Delayed initiation leads to prolonged disease burden. Within the traditional approach, the time to achieve the target uric acid goal of <6 is increased. At an average  allopurinol dose of 100 mg to 300 mg, 66 % of patients were not at the uric acid goal of < 6 [8]. You miss 100% of the shots you don’t take! Even among patients initiated on treatment, only <40% achieve the uric acid goal [9].

Gout affects 9.2 million US adults and has an annual healthcare cost of 24 million dollars. When taken together, delayed initiation of low-dose urate-lowering therapy of the most common cause of inflammatory arthritis contributes to increased healthcare utilization [12], decreased quality of life [13] and persistent premature mortality in gout patients [14].

Results of this publication:

In patients with crystal-proven acute gout arthritis (onset < 7 days), upon early initiation of allopurinol at 300 mg/day along with indomethacin and colchicine (treatment group), pain (measured by visual analog scale) in the first 10 days, and patient-reported gout flare in first 30 days did not differ when compared to initial treatment with only indomethacin and colchicine with delayed allopurinol initiation at day 10 (placebo group). Early initiation of allopurinol helped achieve uric acid at goal by day three and remained at goal throughout the 30 days. Starting allopurinol on day ten meant the uric acid goal was reached only around day 30 [1].

Despite the limitations of being a small, single-center study, this adequately powered study highlights an essential step in synergistically utilizing urate-lowering agents and anti-inflammatory medications to optimize the game plan.

Impact on Rheumatology

Starting Allopurinol early in patients with acute gout arthritis represents a paradigm shift in decades of clinical practice. It helped transform the management of acute gout arthritis, and gout in general, from a theoretical to an evidence-based approach.

It is worth noting that > 90% of gout is managed by Primary care providers [15]. In a survey of PCP, only about 50% of PCP felt their gout management practices are optimal. So, the clarity on the timing and dose of allopurinol initiation, along with the use of indomethacin and colchicine, impacted not only rheumatology but also primary care practices. Again, finding a publication with such broad impact beyond the specialty alone is not common.

For the healthcare system, it has the potential to translate into decreased healthcare resource utilization. Most importantly, achieving optimal gout management will mean enhanced quality of life and improved premature mortality for patients.

Chances in the Tournament

This article is a dark horse on the surface – gout is often not considered by many fellows as a high-flying topic. It’s not as flamboyant as vasculitis, and it’s not as colorful and varied as systemic lupus erythematosus. However, astute viewers will agree this article represents the fundamental essence of the field of rheumatology – continuously reassessing and improving our management of even the oldest and most common diseases to truly impact our patients’ lives. In addition, rheumatology is a part of the healthcare ecosystem where primary care practices are the foundations, and this publication directly impacts primary care practices.

While there have been many developments in managing various rheumatic diseases that have led to significant outcome improvements, given the scale of gout prevalence, we would be hard-pressed to find another paradigm-defining change in rheumatology that has the potential for such a material impact on both disease burden (quality of life, mortality) and healthcare cost/utilization.

We hope our humble report conveys the importance of this advancement and give it the recognition it undoubtedly deserves!

Next scouting report: RAVE Trial

Back to the full list of scouting reports.

See the Q&A on theMednet.org for the Get in the Game region: Are there patients in whom you would avoid initiating of ULT during acute gout flare? 

References

  1. Taylor, T.H., et al., Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial. Am J Med, 2012. 125(11): p. 1126-1134 e7.
  2. Neogi, T., Clinical practice. Gout. N Engl J Med, 2011. 364(5): p. 443-52.
  3. Zhang, W., et al., EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis, 2006. 65(10): p. 1312-24.
  4. Jordan, K.M., et al., British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (Oxford), 2007. 46(8): p. 1372-4.
  5. Yue, T.F. and A.B. Gutman, Effect of Allopurinol (4-Hydroxypyrazolo-(3,4-D)Pyrimidine) on Serum and Urinary Uric Acid in Primary and Secondary Gout. Am J Med, 1964. 37: p. 885-98.
  6. FitzGerald, J.D., et al., 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken), 2020. 72(6): p. 744-760.
  7. Kiefe, C.I., et al., Compliance with post-hospitalization follow-up visits: rationing by inconvenience? Ethn Dis, 1999. 9(3): p. 387-95.
  8. Li-Yu, J., et al., Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout? J Rheumatol, 2001. 28(3): p. 577-80.
  9. Pandya, B.J., et al., Relationship between physician specialty and allopurinol prescribing patterns: a study of patients with gout in managed care settings. Curr Med Res Opin, 2011. 27(4): p. 737-44.
  10. Singh, G., B. Lingala, and A. Mithal, Gout and hyperuricaemia in the USA: prevalence and trends. Rheumatology (Oxford), 2019. 58(12): p. 2177-2180.
  11. Kim, K.Y., et al., A literature review of the epidemiology and treatment of acute gout. Clin Ther, 2003. 25(6): p. 1593-617.
  12. Khanna, P.P., et al., Tophi and frequent gout flares are associated with impairments to quality of life, productivity, and increased healthcare resource use: Results from a cross-sectional survey. Health Qual Life Outcomes, 2012. 10: p. 117.
  13. Khanna, P.P., et al., Long-term therapy for chronic gout results in clinically important improvements in the health-related quality of life: short form-36 is responsive to change in chronic gout. Rheumatology (Oxford), 2011. 50(4): p. 740-5.
  14. Perez-Ruiz, F., et al., Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis, 2014. 73(1): p. 177-82.
  15. Rott, K.T. and C.A. Agudelo, Gout. JAMA, 2003. 289(21): p. 2857-60.