DEC-13-2011 17:57 From•9704772808 DD.J, OF REG!STRAi!ONS 'i OCT28'11/ 001137 lfiiih UnNsrsity of Colorado ~ Anschutz Medical Campus RECEIVED October 24, 201 t Colorado Boatd 0£ Modicnl Ex!lilliners . 1560 'Broadway Suite 1300 Denver, Colorndo 80202 NOV 0 8 2011 The Colorado Medli:el Board RE: Complaint against Gary Weiss, MD/Patient- B Denr Mll111bers of the Inquiry Panel: . . We nre faculty members in the Depa1:1mc11t ofN'elll"Ology of the Univqrs!ly of Co!omdo School of Medicine. Each (lfus is a board-l)(lrtificd nourologist who hos either plll'll~ip~ted in the medical care of-E-or Is familinrwlth the .::&e from C011$ul1lngwith. tho ph)'iiOillttS who provided care. We bel!evethat Gary Weis~, M.D. fulled to provide appropriate care to• B and that bis deviations fi'om the standard of Olll'll caused harm. We would nQf make a complaint lo the Colorado BoalXI of Medical Examiner& unless we believed that Dr, Weiss' conduct was sign! flcantly below the applicable stundaid of care. -B8was aslx1y-tltree year-old patient who died in 2011 afttt having boon under the car~ uf Dr, Weis~ for ~everal yetm1. • B.had been diagnosed with multiple $Clerosis many years earlier and bad entered a secondary progressive p!i115e of the ilbu:•n at least ten years ago. During the secondaty progressivo phMe, patients experience 11 progressive worsening of th~ diaonse. includln$ nerve d81t'lllge and loss. In 2009, Dr. Weiss placed• . . on natalhrumllb (Tysabti). The most seri.o1111 polenlinl complication with the use ofnatalizhnab i~ immunosuppression• related progrcss!varnultifucal leukoencephnlapthy (PML), a rare brain inftlction aeenonly In immunosuppressed patients, which OCCUIS in about ane in 617 MS pQtients who we this drug. The incldenGe i• relllied to duration ofuse (!ncreasos with longer use), prior expolllll'C to the virus (JC vixus) that cau~es PML, attd prior exposure to other lm.tnlU\uSUjlpressanls (which Increases tho risk four.fold). There is a test to Inquire about prior expos11re lo fhe JC virus, but it has jlll!t become ~ommerolally available. It fo1s beeti ii"ee\y available In nuineroua sites'throughout the US as part cf several studies, and many praotitionem have made this &Vfiilable to their patient$, Patient!! are typically screened about every threl) months for PML by routine history IUld o~amination, possibly with the JC virus serology test when available, and with lntermittent brain MRl so!UIS oftbe briiltt, U$Ually about every 12 months. PML is ~li50rder lhal either kills or leaW!I Berlous impa!nnent in a majority of patients who develop it. Thero arc no proven antivirlll strutegies, leaving only tho option of!e\llov!ng the drug ftom tho plllieont's system~)' plasma exchange (PLBX) and possibly using e11pcrhncnlal agents, most ofwhioh w:enot freely available. 011teomein thi& c:onte11t is related 1o the age of the patient, the sctverity oftho patient's multiple sclerosl$ prior to institution ofnntalizumab, and lime li:om onset to time of diagnosis of PML. Thero is n risk mitigation •trategy (REMS) in phtce, as mandated by the FDA. ----··-- ·--SC~L.OFMSOICINE De,-..'t1lnM:intolNGUmtl°'ilY I f'Mil"JWrJC185 I 120310L8f lrtl1Awnut1 EXHIBIT D ! lwru10,C'Xlt1UU4b OEC-13-2011 17•58 N"ext. Ste~ From:9704772808. Belweel\ 2009 and Pebruacy of2011, this patient received approximatoly.19 doses of · . natalizumab, whicllplaced in the category of enhanced risk of developing PML. Dr. Weiss bad previously followed• with brain MRI scans obtained in lus office on a substandard 0.3 Ti:;sla Wlit, for which he dPea the neuroradi\lloglcal reading. We are unaware that he has any radiology tr11i11ing othor than that typically received by a neurologist or that he employs 1111y "over·rf;\Ud" by board-certified radiologist or neuroradiologlst. The lost scan before FebMry of 2011 was August of2010, This August 2010 SCMt showed le&ions oo!ISiBtent with MS but no signs of PML. a ln February 2011, the patient began to note trouble with speech 11t1d right-sided weakness. A brain MRI scan obtained in Dr. Weiss's office lllld read by him revealed new lesions in the left hemisphere of the brain, a finding that is higbly concerning for PML, yet Dr. We.iss took no 11Ctlott in r~ponse to those findings. •was continued on natalb:umab. The JJatient con~nued to worsen, to the point ofbeco111i11g wheelchair-bound, having aplrnsia (severe language disruption), 1111d being ndmitted from• daughter's home to 11 nur3ing home. Dr. Weiss obtained and read a repeat brain MRT scan on May 10, 2011. This soan, whjoh WflB again taken on the 0.3 Tesla.scanner, showed worsening of the l11slons in the left hemisphere. Dr. Wei..'18 took no uctfon in respome and the patient continued to receive nate.llrumnb. Dr. WeiBs obtained and read arepeatbmln MRI scan onJWle20, 2011. This scan, which was again taken on llte 0.3 'resla scanner, Qpp11rently raised the firstconcem fur Dr. Weiss that his patient was affected by PML, Dr. Weiss wllll oul·1>f·~lnte when the MRI results oame to Ills attention and appaiently had not made other plllllll for 110\lrologlcal covotago because hiiJ initial plan was to tt1msfer the patient from the Weatem slope of Colorado to a Glenwood Springs emergency room to perfolTJI a spinal fluid ex:amination to confirm l'ML. Dr. Weiss and his office staff also searched for a location to perlbm1 PLBX, so as to remove the natalixumab from system. The patit411t Wall referred I() us at University uf Colorado Hospital for Ihle p\IIPOfle. a After admission lo the UCH on June 30, 21)11, we reviewed the MRI sew ftom August 2010, Febn.11iy20l l,May201 l, and June20ll and compared thwu to anew scan inoudnstltutlonon the standard 1.5 Tesla su!IIl11er, Both the neurofogistll l!lld the formal ne\ltO?lldiologlst reading · determined that the lesions were not present In A~st 2010, but were appnrent in February of 2011 and hnd sisnitiountly progressed over time, T!ie diagnosis of PML was confirmed by polymEll'lllle bhaln reaction (PCR) testing shQwing evidence of the virus in the cerebro.spinal fluid of the patient. The patient underwent PLEX, and. Ill so recoived IV steroids in an attempt to combat a complication associated with ihls oircumstance, ohnhanced immunological response against th11 PML, known 1111 Immune reconstitution inflsmmatory syndroin~ (IRIS) and E. recurrence of the patient's MS. · We discharged • !Tom Unlvorslty of Colomdo Hospital in stable condition, but• wes affected with tight hemlplegla 1111d aphasla, both of which wcro new 1111d significant impalm1e11ts thahnlUlifestedafter Februlll")' 2011. We have subsequentlylemned that• B-dled in September 2011 and SUBpect that. demise is related to PML, although. we have not r&viewed any medical records subsequent to• E-discharu;e. DEC-13-2011 17•59 From:9704772808 Next, Stefl' Wo would summilrlze out· concerns about Dr. Weiss's care aa the fbllowing: I. The patient wns over 60 when• was placed on natali.oumab, and had been in~ progressive phase (secondary progressive MS -SPMS) oftlte illrtllSs for some t!ms. Nutafo;umnb is only approved for those with relapsing Fonns of th~ illness. Bhad not had relaps'IS for at least 10 yrsity of Colorado School of Medicine ~4d Matthew West, MD Assistant Profcasor, Nem:ology, Univcmiity of Colorado School ofM~dfoine K!l!!JlOS L, et al, L~neet Neurol. 2011 Aug;10(8}:745-S8. Natll!izulllab 1reetment for multiple selcroslsi updated recommendations far patient •ele~tlon and monitoring.