HCQ Withdrawal

Team: HCQ Withdrawal, aka “2legit2quit- Hydroxychloroquine- Why you ‘Can’t Touch This’  drug”

Region: Jump Ball

Base Article: Canadian Hydroxychloroquine Study Group. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med. 1991;324(3):150-154. doi:10.1056/NEJM199101173240303. PMID 1984192

Authors: Belinda Birnbaum, MD- Rheumatologist, Bryn Mawr Medical Specialists Association; Jay Ghadiali, MD- Rheumatologist, Bryn Mawr Medical Specialists Association. Bryn Mawr, PA.

Team Overview

Every Rheumatologist should know that 1991 was a remarkable year.  The first World Wide Web website launched, the former U.S.S.R disbanded, The Duke Blue Devils started their basketball reign with their first NCAA championship, and MC Hammer topped the charts. But it was also the year that one study  would lay the foundation for lupus management for decades.. It’s time to pay homage to one of the GOATs in rheumatology.

In 1991, Dr. Esdaile and his Canadian Colleagues demonstrated that the necessity of hydroxychloroquine (HCQ) was not mere hypothesis or hyperbole but plain-spoken truth; hydroxychloroquine was purposeful to lupus patients, and its withdrawal would prove problematic [1].

We 21st-century rheumatologists take it as a given that HCQ,  once started, should rarely be stopped.  But that wasn’t always the case. While it was known for decades that antimalarials work for lupus [2], the doubters didn’t feel comfortable keeping patients on it long term (the doubters were not just ophthalmologists, but rheumatologists too). Our authors had a hunch it was necessary and safe so they conducted a randomized controlled trial.  Stable patients with SLE on hydroxychloroquine for at least six months were randomized to either continuation of HCQ,  or to the withdrawal of it,  taking a placebo for 24 weeks.

What was the bottom line?   The relative risk of a clinical flare-up was 2.5 times higher (95 percent confidence interval, 1.08 to 5.58) in the patients taking a placebo than in those continuing to take hydroxychloroquine (16 of 22 patients vs. 9 of 25 had flare-ups), and the primary outcome, the time to a flare-up was shorter (P = 0.02).  The secondary outcomes were a change in the prednisone dose and development of a a severe flare. The lupus patients on placebo had to increase their prednisone more and had more severe flares than patients who were taking hydroxychloroquine.  These measurements did not reach statistical significance.  Long-term hydroxychloroquine helps our lupus patients.  Not only is it necessary to initiate hydroxychloroquine at disease diagnosis, but also to continue hydroxychloroquine to prevent flares and progression.

Impact on Rheumatology

The impact of long-term hydroxychloroquine use cannot be understated. There is no other drug available to rheumatologists today with so much benefit and so few adverse events.  Can you think of another DMARD (maybe methotrexate?),that you prescribe more frequently than hydroxychloroquine? Yeah, we didn’t think so.  Can you imagine a time when maintaining a patient on HCQ wasn’t obvious? We can’t, but we are a Gen X and a Millennial. (To any boomer blue ribbon panelists, we think you look great)

Hydroxychloroquine is timeless. No matter what other drug we use for lupus, we know this will always be part of our armamentarium.  It is the steady workhorse we need. Any player or coach knows that a solid defense wins games,  no matter how flashy an offense is.  In that sense, hydroxychloroquine is the tenacious D of rheumatology.

Chances in the Tournament:

When looking at the other contenders, we would like you to ask yourself this question- Where would you be as a rheumatologist without Hydroxychloroquine?  When put this way,  we see our chances as excellent!

While RAVE offered rituximab for ANCA-associated vasculitis,  and ALMS offered mycophenolate mofetil for lupus nephritis, they merely added options to an already available drug, cyclophosphamide. Two trials show the same thing; The drug they are rooting for is better or non-inferior to something else…meh.  Are they a cornerstone for maintenance without causing diarrhea or infusion reactions?  Are they prescribed without the headache of prior authorizations and complicated instructions over proper administration?  No, no they are not.    And let’s talk about cost-effectiveness.  Fans of the Michael Lewis book  “Moneyball” or fans of the movie can learn how the Oakland Athletics won the World Series despite having one of the lowest payrolls in all of Major League Baseball.  Hydroxychloroquine is the “Moneyball” of rheumatology. Sure, it doesn’tfill the stands and stadiums like the high-cost players (yes, you Rituximab; and mycophenolate mofetil, you are no bargain), but it gets the job done and can win championships so we are optimistic. As years have passed, we find more ways it helps our patients. It provides better pregnancy outcomes, it reduces thrombotic events [3,4].  What will it do next?  Cure a global pandemic?  Yeah, no. Not that

More like the song, and unlike MC Hammer’s parachute pants, you can’t touch Hydroxychloroquine; it is too legit.  When the ref tosses up that jump ball, we will easily take possession and win.

Next scouting report: ALMS Trial

Back to the full list of scouting reports.

See the Q&A on theMednet.org for the Jump Ball region: Do you ever consider discontinuing hydroxychloroquine SLE patients in longstanding remission except in cases of overt toxicity?


  1. Canadian Hydroxychloroquine Study Group. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med. 1991;324(3):150-154. doi:10.1056/NEJM199101173240303
  2. PAGE F. Treatment of lupus erythematosus with mepacrine. Lancet. 1951;2(6687):755-758. doi:10.1016/s0140-6736(51)91643-13. Clowse MEB, Eudy AM, Balevic S, et al. Hydroxychloroquine in the pregnancies of women with lupus: a meta-analysis of individual participant data. Lupus Sci Med. 2022;9(1):e000651. doi:10.1136/lupus-2021-000651
  3. Petri M, Konig MF, Li J, Goldman DW. Association of Higher Hydroxychloroquine Blood Levels With Reduced Thrombosis Risk in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2021;73(6):997-1004. doi:10.1002/art.41621
  4. MC Hammer 2legit2quit official video https://youtu.be/HFCv86Olk8E (we recommend skipping to minute 8:30 for the actual song)

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