Joseph Sleiman, MD

Follow @JosephHabibi_MD

Oct 3 • 18 tweets • 158 min read

@MondayNightIBD 1/ 📣 #GITwitter #IBDTwitter
It’s a new🔥#Back2Basics session with #GI #Fellow @JosephHabibi_MD

Let’s talk AZA/6-MP in IBD

✅#IBDPolls 1️⃣&2️⃣👆🏽
✅Role as Mono/combo therapy
✅Escalation consideration
✅TPMT & NUDT15 testing
✅Side effects & counseling

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen 2/ AZA trials in IBD:

🔹Corticosteroids needed to induce remission
🔹Takes ~12 wks for AZA/6MP to become effective, so taper steroids accordingly
🔹AZA/6-MP effective for maintenance of remission (mainly in UC); Not effective for induction

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma 3/ AZA in today’s practice

1⃣CS-sparing monotherapy for maintenance of moderate IBD
2⃣Combo w/ TNFi to
↑ TNFi levels
↓ Ab formation
2nd MOA for severe/complex IBD not responsive to mono💉
Perianal Crohn’s

...⏬

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma 4/ AZA in today’s practice

4⃣Ease of PO
6⃣Cheap
5⃣Experience with drug monitoring
3⃣Safe in🤰 & breastfeeding
pubmed.ncbi.nlm.nih.gov/34686575/
@UmaMahadevanIBD @MLongMD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns 5/ Testing needed on initiation

- TPMT (phenotype/activity++, or genotype) for all
- NUDT15 in East Asian descent
- CBC with Diff, LFT
- EBV IgG in peds ? (see lymphoma risk tweet)
gastrojournal.org/article/S0016-…

@Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger 6/ AZA/6-MP metabolism

🔸AZA -> 6-MP -> 6TG & 6MMP
🔸6TG is responsible for immunosuppressive effect, affect CBC
🔸 6MMP -> affect LFT
🔸 6MMP and 6TG levels depends on TPMT activity

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @novakkerri @SunHoLee15 7/ Thiopurines doses are weight based
🔵AZA 2-2.5mg/kg day
🔵6MP 1-1.5mg/kg/day

6TG level
📎For therapeutic response >236 pmol/8x108 RBC
📎To prevent TNFi antibodies>140 pmol/8x108 RBC

@Flaviostein @amelia_kellar @Iris_Dotan @NickCarman1 @FrostKarenLee @ShimaghavimiMD

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @novakkerri @SunHoLee15 @Flaviostein @amelia_kellar @Iris_Dotan @NickCarman1 @FrostKarenLee @ShimaghavimiMD 8/Why test TMPT & NUDT15?

TPMT actvty⏬:6MP convert less to 6MMP, & more into 6TG:↑↑6TG👉neutropenia

NUDT15 variant also associated w/↑ neutropenia

🔑10% population: Intermediate TPMT actvty: ½ dose

🔑0.3% population: NO enzyme activity:⬆️⬆️risk of cytopenia: ❌use AZA/6MP

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @novakkerri @SunHoLee15 @Flaviostein @amelia_kellar @Iris_Dotan @NickCarman1 @FrostKarenLee @ShimaghavimiMD 9/ 🌟#B2BPearl: Cytopenia or liver tox do not always correlate w 6TG/6MMP levels
🔹Can have neutropenia with low 6TG, or nml cbc w high 6TG
🔹Liver toxicity w 6MMP<5,700 or nml LFT w high 6MMP

🌟#B2BPearl poor man’s 6TG level ✅
Low WBC 3-4 & ⬆️MCV = got the right 6TG level

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @novakkerri 10/ AEs

🤢 Idiosyncratic: flu-like & GI AEs, Pancreatitis
⚠️ BM toxicity: if high 6TG (but sometimes w nml 6TG)
⚠️Hepatotoxicity w/ 6MMP >5700
🦠Risk of infx viral > baterial
🌞NMSC

@GroverDheera @BassiMehak @ayshaslam999 @RomyChamoun @ifrahfatima @halesj126 @yaransarkis

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @novakkerri @GroverDheera @BassiMehak @ayshaslam999 @RomyChamoun @ifrahfatima @halesj126 @yaransarkis 11/ AEs: Rare risk of Lymphoma:

↑after 2 yrs of use
📛EBV-Lymphoma: ++ men > 50
Early-post mononucleosis lymphoma: men < age 35 who were EBV neg and seroconvert
📛HTCL (not EBV related), men < 35

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens 12/ As general rule for thiopurines

🚩Benefit of remission >> risk of lymphoma
🚩Limit in young and older men
🚩Avoid in young men EBV NEG
🚩Reassess if still needed after 2yrs

@my_ueg @Bealoquebea @FachalLaura @BritSocGastro @geteccu @ResearchBsg @PeyrinBiroulet @bruce_sands1

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @my_ueg @Bealoquebea 13a/HM while on AZA/6MP

⚠️Prior to thiopurine start ensure pts up-to-date on vax:
💉Pneumococcal vaccines
💉Influenza Qyr
💉HPV vaccine for pts 13-26 yo

Live vax 🚫CI🚫 on thiopurines

@DrsMeena @Marylandibddoc @ryanungaro @MichaelKappel12 @GI_PharmD @IBDPharmacist

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @my_ueg @Bealoquebea @DrsMeena @Marylandibddoc @ryanungaro @MichaelKappel12 @GI_PharmD @IBDPharmacist 13b/ While on AZA/6MPScreen for:

⚠️ HPV/cervical cancer (Pap smear or Pap&HPV co-testing)
⚠️ Non-melanoma skin Ca (annual skin exam)
⚠️ NO screening tests for lymphoma or pancreatitis

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @my_ueg @Bealoquebea @DrsMeena @Marylandibddoc @ryanungaro @MichaelKappel12 @GI_PharmD @IBDPharmacist 14/ Monitoring Practice for AZA

- Check CBC and LFT 2-4 weeks when initiating or changing dose, then q3-6 months
- Continued discussion of risk/benefit, especially with young men <35 or >65
- Metabolites levels (TDM)

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @my_ueg @Bealoquebea @DrsMeena @Marylandibddoc @ryanungaro @MichaelKappel12 @GI_PharmD @IBDPharmacist 15/ Interpreting TDM
🔹 ⬇️6TG,⬇️6MMP
👉🏼 Inadequate dosing
👉🏼 Nonadherence

🔹Therapeutic 6TG
If 🔥ds, change MOA

🔹⬇️6TG, ⬆️6MMP= ⬆️TPMT activity
👉🏼⬇️dose AZA/6MP + Add Allopurinol to block XO pathway & convert more 6MP to 6TG

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @my_ueg @Bealoquebea @DrsMeena @Marylandibddoc @ryanungaro @MichaelKappel12 @GI_PharmD @IBDPharmacist 16/ De-escalation AZA may be considered in
⏺️Combo therapy w/ good long-term remission, provided close FU w/ TNFi TDM, biomarkers & C-🔦

⏺️>1-2 yrs use of AZA in pts w/ concern of malignancy, w/ other treatment options available

Also,3⃣ this User guide pubmed.ncbi.nlm.nih.gov/31887444/en

@MondayNightIBD @NavreetChowlaMD @MilestoneIBD @IBD_FloMD @tinahamd @DrCoreySiegel @HorstIBDDoc @MLongMD @LauraRaffalsMD @doc_ibd @IBDBen @IBDHorizons @IBD_Houston @IrisWangMD @LoriPlung @vaibhav_manu @KatieFalloonMD @amneethansmd @ManuelBragaMD @Chatterjee_MD @SuhaAbushamma @UmaMahadevanIBD @UCLAHealth @SCKimCHP @dunleavy_katie @TandonKp @RahulSDalalMD @nandanpg @DrScottDLee @DushDahiya @ownyourcrohns @Khanna_S @KhushbooSGala @Manik_aggIM @VictorChedidMD @DrMikeDolinger @MountSinaiGI @HelmsleyTrust @BowelUltrasound @IBDMD @KrugCleveland @RuneWilkens @my_ueg @Bealoquebea @DrsMeena @Marylandibddoc @ryanungaro 17/ Thank you for joining us, lots more to talk about in AZA & IBD, but hope this was a good primer for debates and questions.

Please find these excellent high-yield summaries from #MondaynightIBD archives by
@JeanDonet, @DrRosenIBD & @DrMalSimons

Take the #PostB2B #IBDPolls

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More from @JosephHabibi_MD

Joseph Sleiman, MD

@JosephHabibi_MD

May 16

@MondayNightIBD @BassiMehak @abbvie @JanssenUS @ferring @TakedaPharma #PreConvo #IBDPoll1⃣

🆓#CME bit.ly/3wdwE7J

25y/oM w refractory #UlcerativeColitis undergo colectomy w IPAA. Takes acetaminophen PRN headaches & drinks a🍷glass w dinner. Presents for a routine f/up visit. labs: Alk Phos 250. What is the most likely cause of this AP?

@MondayNightIBD @BassiMehak @abbvie @JanssenUS @ferring @TakedaPharma #PreConvo #IBDPoll2⃣

🆓#CME bit.ly/3wdwE7J

What is the most common extra-intestinal manifestation #EIM in patients living with #IBD?

@MondayNightIBD @BassiMehak @abbvie @JanssenUS @ferring @TakedaPharma 1/⬆️ EIMs in #IBD
⭐️ CD > UC.
⭐️ Colon involvement

💣 Pathol:
⭐️ Direct result of bowel disease (e.g kidney stone from oxalate malabsorption )
⭐️ Influx of mononuclear cells activated in the intestine➡️another organ
⭐️ Systemic Immune activation independent of gut🔥

Joseph Sleiman, MD

@JosephHabibi_MD

Mar 31, 2020

Let’s pause for a second, and remember two major #stigma spreading around as contagiously as #COVID19. 🦠
1️⃣Ethnicity of the virus and
2️⃣wearing #PPE

I’m addressing 2️⃣ today, but for more guidance on 1️⃣, & more social Do’s and don’ts, please refer to 👉unicef.org/documents/soci…

To summarize the ongoing debate: “Absence of evidence is NOT evidence of absence”. A half full glass 😷 can be better than none at all. This 🏴&🏳️ system is leading to two issues:
1️⃣ opportunity to incentivize PPE production is lost
2️⃣ STIGMA against those who choose to don.

https://twitter.com/squeenbryant/status/1244522141804040194

If you have 12 minutes to spare, enjoy this well illustrated thesis on the topic, it might change your mind. @medpedshosp

https://twitter.com/medpedshosp/status/1244626739751538689

Joseph Sleiman, MD

@JosephHabibi_MD

Jun 12, 2019

10 things IMG (and USMG) applicants should know for the 2020 residency MATCH: I can’t help but recall how stressful the application journey was one year ago. I hope this thread helps out (instead of adding stress)! @ERAS @AAMC

Build your CV: it helps as you are requesting letters from mentors, or basically any email you're sending. Have a clear CV that speaks of your accomplishments. Do not miss a certificate or work in progress. Here is a link to how to do a cover letter.

https://twitter.com/ShreyaTrivediMD/status/1134263749689430016

Before programs see your application & statement letter, look at it yourself. Know your goals, or at least outlines of your goals. Know your weaknesses and SHOW that you are working on them. Practice your ONE LINER. This will improve your statement letter and application.

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