Clinical Policy: Immune Globulins Reference Number: ERX.SPA.134 Effective Date:

Transcription

1 Clinical Plicy: Reference Number: ERX.SPA.134 Effective Date: Last Review Date: Revisin Lg See Imprtant Reminder at the end f this plicy fr imprtant regulatry and legal infrmatin. Descriptin The fllwing are immune glbulins requiring prir authrizatin: Bivigam, Carimune NF, Cuvitru, Cytgam, Flebgamma DIF, GamaSTAN S/D, Gammagard liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex -C, Hizentra, Hyqvia, Octagam 5%, Octagam 10%, and Privigen. FDA Apprved Indicatin(s) Brand Name ROA PI ITP CIDP KS MMN CLL VPPX Bivigam IV x Carimune NF IV x x Cuvitru SC x Flebgamma DIF IV x x (10% nly) GamaSTAN S/D IM x Gammagard Liquid IV, SC x x (IV nly) Gammagard S/D Less IgA IV x x x x Gammaked IV, SC x x (IV nly) x (IV nly) Gammaplex IV x x Gamunex-C IV, SC x x (IV nly) x (IV nly) Hizentra SC x x HyQvia SC x Octagam IV x (5% nly) x (10% nly) Privigen IV x x x ROA = rute f administratin; CIDP = chrnic inflammatry demyelinating plyneurpathy; CLL = B-cell chrnic lymphcytic leukemia; PI = primary humral immundeficiency; ITP = idipathic thrmbcytpenic purpura; KS = Kawasaki syndrme; MMN = multifcal mtr neurpathy; VPPX = viral prphylaxis (fr hepatitis A, measles, varicella, rubella) Cntents: I. Initial Apprval Criteria A. Chrnic Lymphcytic Leukemia Infectin Prphylaxis B. Dermatmysitis/Plymysitis C. Inflammatry Demyelinating Plyneurpathy (Acute/Guillain-Barre Syndrme r Chrnic) D. Idipathic Thrmbcytpenia Purpura (Acute r Chrnic) E. Kawasaki Syndrme Aneurysm Preventin F. Kidney Transplant G. Multifcal Mtr Neurpathy H. Multiple Myelma I. Multiple Sclersis J. Myasthenia Gravis Or Lambert Eatn Myasthenic Syndrme K. Nenatal/Fetal Allimmune Thrmbcytpenia L. Paraneplastic Neurlgic Syndrme M. Parvvirus B19 Infectin and Anemia N. Pediatric Human Immundeficiency Virus (HIV) Infectin Prphylaxis O. Pemphigus Vulgaris, Pemphigus Fliaceus, Bullus Pemphigid, Mucus Membrane Pemphigid (a.k.a. Cicatricial Pemphigid, Epidermlysis Bullsa Acquisita) P. Viral Prphylaxis fr Hepatitis A, Measles, Varicella, Rubella Viruses Q. Primary Immundeficiencies R. Stiff Persn Syndrme Page 1 f 28

2 II. Cntinued Therapy III. Diagnses/Indicatins fr which cverage is NOT authrized IV. Appendices/General Infrmatin V. Dsage and Administratin VI. Prduct Availability VII. References Plicy/Criteria Prvider must submit dcumentatin (such as ffice chart ntes, lab results r ther clinical infrmatin) supprting that member has met all apprval criteria. It is the plicy f health plans affiliated with Envlve Pharmacy Slutins that immune glbulins are medically necessary when the fllwing criteria are met: I. Initial Apprval Criteria A. B-Cell Chrnic Lymphcytic Leukemia Infectin Prphylaxis (must meet all): 1. Diagnsis f B-cell CLL; 2. Prescribed by r in cnsultatin with an hematlgy/nclgy specialist r immunlgist; 3. Current (within the last 6 mnths) hypgammaglbulinemia as evidenced by tw separate measurements f immunglbulin G (IgG) level < 500 mg/dl; 4. Dcumentatin f ne f the fllwing (a r b): a. One bacterial infectin within the last 6 mnths requiring cnsultatin r treatment with an infectius disease specialist; b. Tw r mre bacterial infectins within the last 12 mnths requiring IV antibitic infusin therapy in the hme r in the hspital; 5. Dse des nt exceed ne f the fllwing (a r b): a. 400 mg/kg IV every 4 weeks; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel B. Dermatmysitis, Plymysitis (ff-label) (must meet all): 1. Diagnsis f dermatmysitis (DM) r plymysitis (PM); 2. Prescribed by r in cnsultatin with a dermatlgist, neurlgist, r neurmuscular specialist; 3. Failure f a 4-mnth trial f a systemic crticsterid (e.g., prednisne) in cmbinatin with ne f the fllwing immunsuppressive agents, bth at up t maximally indicated dses unless cntraindicated r clinically significant adverse effects are experienced: methtrexate, azathiprine, cyclphsphamide, mycphenlate mfetil, tacrlimus, cyclsprine (see Appendix D); 4. Dse des nt exceed ne f the fllwing (a r b): a. 2 g/kg IV per mnth; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel C. Inflammatry Demyelinating Plyneurpathy (Acute/Guillain-Barre Syndrme r Chrnic) (must meet all): 1. Diagnsis f acute inflammatry demyelinating plyneurpathy (AIDP)/Guillain-Barre syndrme (GBS) r CIDP; 2. Prescribed by r in cnsultatin with a neurlgist r neurmuscular specialist; 3. Member meets ne f the fllwing (a h): a. Inability t stand r walk at least 30 feet withut assistance; b. ICU admissin required fr aspiratin r mechanical ventilatin; c. Miller-Fisher syndrme; d. Inability t raise head against gravity; Page 2 f 28

3 e. Severe bulbar palsy (e.g., impaired gag reflex, dysarthria and/r dysphagia); f. Bilateral facial weakness; g. Autnmic dysfunctin (e.g., unexplained dysrhythmia, bld pressure fluctuatins, significant bwel r bladder invlvement); h. Disease is prgressive r relapsing fr mre than 2 mnths; 4. Dse des nt exceed ne f the fllwing (a, b, c, r d): a. 2 g/kg IV per mnth; b. Lading dse 2 g/kg IV given in divided dses ver tw t five cnsecutive days, fllwing by maintenance dse f 1 g/kg IV every 3 mnths; c. SC: nce weekly (initial dse shuld be 1.37 x previus initial IV dse, starting 1 week after last IVIG infusin); d. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel D. Idipathic Thrmbcytpenic Purpura (Acute r Chrnic) (must meet all): 1. Diagnsis f acute r chrnic ITP; 2. Prescribed by r in cnsultatin with a hematlgist; 3. Member meets ne f the fllwing (a r b): a. Failure f ne f the fllwing at up t maximally indicated dses unless cntraindicated r clinically significant adverse effects are experienced: i. Systemic crticsterids (e.g., prednisne); ii. Rh(D) immune glbulin (RhIG); *Prir authrizatin is required fr RhIG b. Pregnant; 4. Member meets ne f the fllwing (a e): a. Current (within the last 30 days) platelet cunt < 30,000/µL; b. Actively bleeding; c. High risk f life-threatening hemrrhage; d. Splenectmy is scheduled; e. Pregnant; 5. Dse des nt exceed ne f the fllwing (a, b, r c): a. 1 g/kg IV as a single dse; b. Initial lading dse f 2 g/kg IV, fllwed by a maintenance dse f 1 g/kg IV every 3 weeks; c. Dse is supprted by practice guidelines r peer-reviewed literatures fr the relevant fflabel E. Kawasaki Syndrme Aneurysm Preventin (must meet all): 1. Diagnsis f Kawasaki syndrme r incmplete (atypical) Kawasaki disease; 2. Prescribed by r in cnsultatin with a cardilgist, allergist, immunlgist, infectius disease specialist, r rheumatlgist; 3. Prescribed cncurrently with aspirin therapy, unless cntraindicated r clinically significant adverse effects are experienced; 4. Dse des nt exceed ne f the fllwing (a, b, c, r d): a. 1 g/kg IV as a single infusin; b. 400 mg/kg IV daily fr 4 cnsecutive days; c. 2 g/kg IV as a single infusin; d. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel Apprval duratin: One time apprval (1 mnth) F. Kidney Transplant (ff-label) (must meet all): 1. Member meets ne f the fllwing (a r b): Page 3 f 28

4 a. If prescribed prir t kidney transplant, member has high levels f anti-dnr antibdies (i.e., member is highly sensitized t the tissue f the majrity f living r cadaveric dnrs because f nn-self human leukcyte antigen (HLA) r ABO incmpatibility); b. If prescribed fllwing kidney transplant, used fr the treatment f antibdy-mediated rejectin; 2. Prescribed by a nephrlgist, transplant specialist, r hematlgist/nclgist; 3. Dse des nt exceed ne f the fllwing (a r b): a. 140 g IV per infusin; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel G. Multifcal Mtr Neurpathy (must meet all): 1. Diagnsis f MMN; 2. Prescribed by r in cnsultatin with a neurlgist r neurmuscular specialist; 3. Dse des nt exceed ne f the fllwing (a r b): a. 2.4 g/kg IV per mnth; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel H. Multiple Myelma Infectin Prphylaxis (ff-label) (must meet all): 1. Diagnsis f multiple myelma (MM) with stable plateau phase disease; 2. Prescribed by r in cnsultatin with an hematlgy/nclgy specialist, r immunlgist; 3. Current (within the last 6 mnths) hypgammaglbulinemia as evidenced by tw separate measurements f immunglbulin G (IgG) level < 600 mg/dl; 4. Dcumentatin f ne f the fllwing (a r b): a. One bacterial infectin within the last 6 mnths requiring cnsultatin r treatment with an infectius disease specialist; b. Tw r mre bacterial infectins within the last 12 mnths requiring IV antibitic infusin therapy in the hme r in the hspital; 5. Dse des nt exceed ne f the fllwing (a r b): a. 400 mg/kg IV every 3 weeks; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel I. Multiple Sclersis (ff-label) (must meet all): 1. Diagnsis f relapsing remitting multiple sclersis (MS); 2. Prescribed by r in cnsultatin with a neurlgist; 3. Failure f three FDA-apprved disease-mdifying MS therapies (e.g., Avnex, Aubagi, Betasern, Rebif, Cpaxne, Tecfidera, Gilenya) at up t maximally indicated dses unless cntraindicated r clinically significant side effects are experienced; *Prir authrizatin is required fr MS therapies 4. Dse des nt exceed ne f the fllwing (a r b): a. Initial lading dse f 400 mg/kg IV fr 5 days, fllwed by maintenance dse f 1 g/kg IV per mnth; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel J. Myasthenia Gravis (MG) Or Lambert Eatn Myasthenic Syndrme (LEMS) (ff-label) (must meet all): 1. Diagnsis f myasthenia gravis (MG) r Lambert Eatn myasthenic syndrme (LEMS); 2. Prescribed by r in cnsultatin with a neurlgist r neurmuscular specialist; 3. Member meets ne f the fllwing (a, b, r c): Page 4 f 28

5 a. Acute crisis (e.g., vital capacity less than 1 L/min, inability t walk 100 ft withut assistance, intubatin, dysphagia with aspiratin, mechanical ventilatin); b. Thymectmy surgery is scheduled; c. Failure f bth f the fllwing at up t maximally indicated dses, unless cntraindicated r clinically significant adverse effects are experienced (i and ii): i. Chlinesterase inhibitr (e.g., pyridstigmine); ii. Systemic crticsterid (e.g., prednisne) r immunsuppressant (e.g., azathiprine); 4. Dse des nt exceed ne f the fllwing (a r b): a. 2 g/kg IV per treatment curse; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel K. Nenatal/Fetal Allimmune Thrmbcytpenia (ff-label) (must meet all): 1. Diagnsis f nenatal allimmune thrmbcytpenia (NAIT) r fetal allimmune thrmbcytpenia (FAIT); 2. Prescribed by r in cnsultatin with a hematlgist/nclgist r immunlgist; 3. Member meets ne f the fllwing (a, b, c, r d): a. Previus pregnancy affected by FAIT and father is hmzygus fr human platelet antigen (HPA) gentype (e.g., HPA-1a); b. Serlgical cnfirmatin f NAIT as evidenced by maternal-fetal HPA incmpatibility; c. At 20 weeks, crdcentesis reveals fetal platelets < 100 x 10 9 /L; d. Symptmatic nenates with bth f the fllwing (i and ii): i. Current (within the last 30 days) severe thrmbcytpenia < 50 x 10 9 platelets/l; ii. At high risk f develping intracranial hemrrhage when washed irradiated maternal platelets are nt available, have nt been successful, have becme intlerable, r are cntraindicated; 4. Dse des nt exceed ne f the fllwing (a r b): a. 2 g/kg IV per week; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel L. Paraneplastic Neurlgical Syndrme (ff-label) (must meet all): 1. Diagnsis f ne f the fllwing subtypes f paraneplastic neurlgical syndrme (a r b): a. Opsclnus-myclnus-syndrme; b. Anti-NMDA encephalitis; 2. Prescribed by r in cnsultatin with a neurlgist, neurmuscular specialist, r nclgist; 3. Fr psclnus-myclnus-syndrme: Failure f at least ne systemic crticsterid (e.g., prednisne) at up t maximally indicated dses, unless cntraindicated r clinically significant adverse effects are experienced; 4. Dse des nt exceed ne f the fllwing (a, b, c, r d): a. 2 g/kg IV per mnth; b. 0.4 g/kg IV per day; c. 200 mg/kg SC per week; d. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel M. Parvvirus B19 Infectin and Anemia (ff-label) (must meet all): 1. Diagnsis f anemia secndary t chrnic parvvirus B19 infectin; 2. Prescribed by r in cnsultatin with a hematlgy/nclgy specialist, infectius disease/hiv specialist, r immunlgist; 3. Current (within the last 30 days) severe anemia (i.e., Hgb <10 r Hct < 30) due t bne marrw suppressin; 4. Dse des nt exceed ne f the fllwing (a r b): Page 5 f 28

6 a. Initial dse f 2 g/kg/day fr up t 5 days, fllwed by maintenance dse f 400 mg/kg IV every 4 weeks; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel N. Pediatric Human Immundeficiency Virus (HIV) Infectin Prphylaxis (ff-label) (must meet all): 1. Prescribed fr prphylaxis f serius bacterial infectin in a child wh has human immundeficiency virus (HIV); 2. Prescribed by r in cnsultatin with an HIV r infectius disease specialist; 3. Member meets ne f the fllwing (a f): a. Current (within the last 6 mnths) hypgammaglbulinemia as evidenced by tw separate measurements f serum IgG cncentratin less than 250 mg/dl; b. Recurrent serius bacterial infectins (defined as tw r mre infectins such as bacteremia, meningitis, r pneumnia in a 12 mnth perid); c. Inadequate antibdy respnse t prtein/plysaccharide vaccines (e.g., measles, pneumcccal, and/r Haemphilus influenzae type b); d. Lives in an area where measles is highly prevalent and has nt develped an antibdy respnse after tw dses f measles, mumps, and rubella virus live vaccine; e. Expsure t measles (requires a single dse); f. Chrnic brnchiectasis that is subptimally respnsive t antimicrbial and pulmnary therapy; 4. Dse des nt exceed ne f the fllwing (a r b): a. 400 mg/kg IV every 2 weeks; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel O. Pemphigus Vulgaris, Pemphigus Fliaceus, Bullus Pemphigid, Mucus Membrane Pemphigid (a.k.a. Cicatricial Pemphigid), Epidermlysis Bullsa Acquisita (ff-label) (must meet all): 1. Diagnsis f ne f the fllwing (a, b, c, r d): a. Pemphigus vulgaris; b. Pemphigus fliaceus; c. Bullus pemphigid, mucus membrane pemphigid (a.k.a. cicatricial pemphigid); d. Epidermlysis bullsa acquisita; 2. Prescribed by r in cnsultatin with a dermatlgist r immunlgist; 3. Failure f at least ne crticsterid (e.g., prednisne) and at least ne immunsuppressive agent (e.g., cyclphsphamide, azathiprine, mycphenlate mfetil) at up t maximally indicated dses unless cntraindicated r clinically significant adverse effects are experienced; 4. Dse des nt exceed ne f the fllwing (a, b, c, r d): a. 2 gm/kg every 4 weeks; b. 400 mg/kg/day fr 5 days (1 cycle nly; may repeat up t three times in a 6-mnth perid); c. 300 mg/kg/day fr 5 days at mnthly intervals (fr up t 3 cycles); d. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel P. Primary Immundeficiencies (must meet all): 1. Diagnsis f primary immundeficiencies (PI), including any f the fllwing (a g): a. Agammaglbulinemia (e.g., X-linked, cngenital); b. Cmmn variable immundeficiency (CVID); c. Cngenital hypgammaglbulinemia; Page 6 f 28

7 d. Immundeficiency with near/nrmal IgM (absent IgG, IgA) (als knwn as Hyper IgM syndrme); e. Selective immundeficiency (e.g., selective IgA, IgM, r IgG subclass); f. Severe cmbined immundeficiency disrders (SCID) (e.g., X-SCID, jak3, ZAP70, ADA, PNP, RAG defects, ataxia telangiectasia, Wisktt-Aldrich syndrme, DiGerge syndrme); g. Subclass deficiency r functinal antibdy deficiency (see Appendix D); 2. Prescribed by r in cnsultatin with an immunlgist; 3. Current (within the last 6 mnths) hypgammaglbulinemia (belw nrmal fr age) as evidenced by tw separate measurements f immunglbulin level (see Appendix E); 4. Dcumentatin f ne f the fllwing (a, b, r c): a. One bacterial infectin within the last 6 mnths requiring cnsultatin r treatment with an infectius disease specialist; b. Tw r mre bacterial infectins within the last 12 mnths requiring IV antibitic infusin therapy in the hme r in the hspital; c. Inadequate antibdy respnse t prtein/plysaccharide vaccines (e.g., tetanus, diphtheria, pneumcccal); 5. Dse des nt exceed ne f the fllwing (a, b, c, r d): a. 800 mg/kg IV every 4 weeks; b. 600 mg/kg SC every 4 weeks; c. SC: nce weekly (initial dse shuld be 1.37 x previus initial IV dse, starting 1 week after last IGIV infusin); d. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel Q. Viral Prphylaxis fr Hepatitis A, Measles, Varicella, Rubella Viruses (must meet all): 1. Request is fr ne f the fllwing indicatins (a, b, r c): a. Hepatitis A pst-expsure/high-risk prphylaxis and meets bth f the fllwing (i and ii): i. Hepatitis A expsure r at high risk fr expsure as fllws (a r b): a) Expsure t hepatitis A in the past 2 weeks (e.g., husehld cntact, sexual cntact, sharing illicit drugs with smene psitive fr hepatitis A, regular babysitters/caretakers, fd handlers at the same establishment as ne wh is psitive fr hepatitis A) AND des nt have clinical manifestatins f hepatitis A; b) Traveling t r wrking in an area endemic fr hepatitis A; ii. Meets at least ne f the fllwing (a, b, r c): a) Hepatitis A vaccine is lcally unavailable; b) Histry f severe allergic reactin (anaphylaxis) t the hepatitis A vaccine; c) If either expsed t the virus r traveling in 2 weeks t an area endemic fr hepatitis A, then (1, 2, r 3): 1) Age < 1 year r > 40 years; 2) Chrnic liver disease r ther chrnic medical cnditin; 3) Immuncmprmised; b. Measles (rubela) pst-expsure prphylaxis and meets all f the fllwing (i, ii, iii, and iv): i. Expsure t measles within the past 6 days; ii. Member has nt previusly received a measles vaccine; iii. Member has nt previusly had measles; iv. Meets at least ne f the fllwing (a f): a) Measles vaccine is lcally unavailable; b) Histry f severe allergic reactin (anaphylaxis) t the measles vaccine; c) Pregnancy; d) Immuncmprmised; e) Has been > 3 days since expsure; f) Age < 12 mnths; Page 7 f 28

8 c. Chickenpx (varicella) pst-expsure prphylaxis and meets all f the fllwing (i, ii, iii, and iv): i. Expsure t varicella within the past 10 days; ii. Member lacks immunity t varicella; iii. Varicella zster immune glbulin (VZIG) is currently unavailable; iv. Meets any f the fllwing (a e): a) Varicella vaccine is lcally unavailable; b) Histry f a severe allergic reactin (anaphylaxis) t the varicella vaccine; c) Pregnancy; d) Immuncmprmised; e) Newbrn f mther wh had varicella frm 5 days befre t 2 days after delivery; d. Rubella pst-expsure prphylaxis (i and ii): i. Recent expsure t rubella; ii. Member is pregnant; 2. Dse des nt exceed ne f the fllwing (a e): a. Hepatitis A (i, ii, r iii): i. 0.1 ml/kg IM nce; ii. Fr anticipated expsure up t 2 mnths: 0.2 ml/kg IM nce; iii. Fr anticipated expsure 2 mnths r lnger: 0.2 ml/kg IM every 2 mnths; b. Measles (i r ii): i. 15 ml IM nce; ii. 400 mg/kg IV nce; c. Varicella: 1.2 ml/kg IM nce; d. Rubella: 0.55 ml/kg IM nce; e. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel Apprval duratin: Hepatitis A: Up t 6 mnths All ther indicatins: One time apprval (1 mnth) R. Stiff Persn Syndrme (ff-label) (must meet all): 1. Diagnsis f stiff persn syndrme (als knwn as Mersch-Wltmann syndrme); 2. Prescribed by r in cnsultatin with a neurlgist r neurmuscular specialist; 3. Failure f a benzdiazepine (e.g., diazepam) r baclfen at up t maximally indicated dses, unless cntraindicated r clinically significant adverse effects are experienced; 4. Dse des nt exceed ne f the fllwing (a r b): a. 2 g/kg IV per treatment curse; b. Dse is supprted by practice guidelines r peer-reviewed literature fr the relevant fflabel S. Other diagnses/indicatins 1. Refer t ERX.PA.01 if diagnsis is NOT specifically listed under sectin III (Diagnses/Indicatins fr which cverage is NOT authrized). II. Cntinued Therapy A. Kawasaki Syndrme/Incmplete (Atypical) Kawasaki Disease, Viral Prphylaxis (Hepatitis A, Measles, Varicella, Rubella) (must meet all): 1. Member must be re-evaluated using initial apprval criteria. Apprval duratin: B. All Other Indicatins in Sectin I (must meet all): 1. Currently receiving medicatin via Centene benefit r member has previusly met initial apprval criteria; 2. Member is respnding psitively t therapy (see Appendix D fr examples); 3. If request is fr a dse increase, request meets ne f the fllwing (a r b): Page 8 f 28

9 a. Dse titratin r cnversin is apprpriate per package insert labeling; b. New dse is supprted by practice guidelines r peer-reviewed literature fr the relevant ff-label C. Other diagnses/indicatins (must meet 1 r 2): 1. Currently receiving medicatin via a health plan affiliated with Envlve Pharmacy Slutins and dcumentatin supprts psitive respnse t therapy. Apprval duratin: Duratin f request r 6 mnths (whichever is less); r 2. Refer t ERX.PA.01 if diagnsis is NOT specifically listed under sectin III (Diagnses/Indicatins fr which cverage is NOT authrized). III. Diagnses/Indicatins fr which cverage is NOT authrized: A. Nn-FDA apprved indicatins, which are nt addressed in this plicy, unless there is sufficient dcumentatin f efficacy and safety accrding t the ff-label use plicy ERX.PA.01 r evidence f cverage dcuments; B. The fllwing cnditins are cnsidered nt medically necessary: 1. Acquired factr VIII inhibitrs; 2. Adrenleukdystrphy; 3. Alzheimers Disease; 4. Amytrphic lateral sclersis; 5. Angiedema; 6. Antiphsphlipid syndrme; 7. Aplastic anemia; 8. Asthma; 9. Autism; 10. Autimmune chrnic urticaria; 11. Behçet's syndrme; 12. Cardimypathy, acute; 13. Chrnic fatigue syndrme; 14. Chrnic sinusitis; 15. Cicatricial pemphigid; 16. Cmplex pain reginal syndrme (CPRS) ; 17. Cngenital heart blck; 18. Cystic fibrsis; 19. Dermatsis, autimmune blistering; 20. Diabetes mellitus; 21. Diamnd-Blackfan anemia; 22. Dysautnmia, acute idipathic; 23. Eczema; 24. Encephalpathy, acute; 25. Endtxemia; 26. Epilepsy; 27. Gdpasture s syndrme; 28. Hemlytic transfusin reactin; 29. Hemlytic-uremic syndrme; 30. Hemphagcytic syndrme; 31. Idipathic lumbsacral flexpathy; 32. Immune-mediated neutrpenia; 33. Inclusin bdy mysitis; 34. Infectin preventin and cntrl in newbrns; 35. Intractable seizures; 36. Leukemia, acute lymphblastic; 37. Lwer mtr neurn syndrme; 38. Multiple sclersis - primary prgressive r secndary types; 39. Myalgia, mysitis, unspecified; Page 9 f 28

10 40. Myelpathy, HTLV-I assciated; 41. Nephrpathy, membranus; 42. Nephrtic syndrme; 43. Nn-immune thrmbcytpenia; 44. Ophthalmpathy, euthyrid; 45. Oral use; 46. Otitis media, recurrent; 47. Paraneplastic cerebellar degeneratin; 48. Paraprteinemic neurpathy; 49. Pediatric autimmune neurpsychiatric disrders assciated with streptcccal infectin (PANDAS); 50. POEMS syndrme (see General Infrmatin Sectin IV fr definitin); 51. Plyarteritis ndsa; 52. Prgressive lumbsacral plexpathy; 53. Radiculneuritis, Lyme; 54. Rasmussen's syndrme; 55. Recurrent titis media; 56. Recurrent spntaneus pregnancy lss; 57. Refractriness t platelet transfusin; 58. Reiter's syndrme; 59. Renal failure, acute; 60. Rheumatid arthritis (adult and juvenile); 61. Sclerderma; 62. Secndary immundeficiencies induced by bilgic therapies; 63. Sensry neurpathy; 64. Systemic Lupus Erythematsis; 65. Systemic vasculitides; 66. Thrmbcytpenia (nn-immune); 67. Vasculitis assciated with ther cnnective tissue diseases; 68. Vgt-Kyanagi-Harada syndrme; 69. Wegener s granulmatsis. IV. Appendices/General Infrmatin Appendix A: Abbreviatin/Acrnym Key ACTH: adrencrtictrpic hrmne AIDP: acute inflammatry demyelinating plyneurpathy CIDP: chrnic inflammatry demyelinating plyneurpathy CLL: chrnic lymphcytic leukemia CVID: cmmn variable immundeficiency DIF: dual inactivatin plus nanfiltratin FAIT: fetal allimmune thrmbcytpenia FDA: Fd and Drug Administratin GBS: Guillain Barre Syndrme HIV: human immundeficiency virus HLA: human leukcyte antigen HPA: human platelet antigen IG: immune glbulin IgA: immune glbulin A IgG: immune glbulin G IgM: immune glbulin M IMIG: immune glbulin (IM rute) ITP: immune thrmbcytpenic purpura IVIG: immune glbulin (IV rute) MMN: multifcal mtr neurpathy NAIT: nenatal allimmune thrmbcytpenia NF: nanfiltered NMDA: N-methyl D-aspartate RhIG: Rh(D) immune glbulin SCID: severe cmbined immundeficiency disrders SCIG: immune glbulin (SC rute) PI: primary [humral] immundeficiency SC: subcutaneus S/D: slvent/detergent treated VZIG: varicella zster immune glbulin Appendix B: Therapeutic Alternatives This table prvides a listing f preferred alternative therapy recmmended in the apprval criteria. The drugs listed here may nt be a frmulary agent fr all relevant lines f business and may require prir authrizatin. Page 10 f 28

11 Drug Name Dsing Regimen Dse Limit/ Maximum Dse baclfen (Liresal ) diazepam (Valium ) pyridstigmine (Mestinn ); Mestinn Timespan (pyridstigmine extended release) Rhphylac, WinRh SDF (Rh(D) immune glbulin) Immunsuppressive agents azathiprine (Imuran ) Stiff Persn Syndrme* 20 mg PO BID r TID, r 50 t 1,600 mcg/day intrathecally Stiff Persn Syndrme* 20 t 80 mg/day PO (given in divided dses) Myasthenia Gravis Immediate Release (IR) tablets and syrup Adults: 60 t 1,500 mg PO daily in divided dses (avg 600 mg PO daily) Pediatrics*: 1 mg/kg PO Q4 t 6 hrs Extended Release 180 t 540 mg PO QD r BID Idipathic Thrmbcytpenic Purpura in nn-splenectmized, Rh (D) antigen psitive patients Initial: 50 mcg/kg IV Maintenance Therapy: 25 t 60 mcg/kg IV Dermatmysitis/Plymysitis*, Myasthenia Gravis* 2 mg/kg PO QD r 50 mg/day PO up t 2 t 3 mg/kg/day PO: 80 mg/day IT: 1600 mcg/day Daily dses needed t cntrl the disease can be as high as 100 t 200 mg/day in sme patients IR: 1,500 mg/day (adults) r 7 mg/kg/day (pediatrics) ER: 1,080 mg/day 75 mcg/kg* 3 mg/kg/day cyclphsphamide (Cytxan ) cyclsprine (Gengraf, Neral, Sandimmune ) methtrexate (Rheumatrex ) mycphenlate mfetil (Cellcept ) Pemphigus vulgaris and assciated cnditins* 2 t 3 mg/kg/day PO Dermatmysitis/Plymysitis* 1 t 3 mg/kg/day PO QD r 500 mg IV every 2 weeks fr 6 dses Pemphigus vulgaris and assciated cnditins* 50 t 75 mg/day PO r pulsed regimen f 500 mg IV n day, and then every 4 weeks thereafter in cmbinatin with ral cyclphsphamide and dexamethasne Dermatmysitis/Plymysitis* 5 t 10 mg/kg/day PO Dermatmysitis/Plymysitis* 10 t 25 mg/week PO/IV Dermatmysitis/Plymysitis* 250 t 500 mg PO BID, increasing t a target dse f 1,500-3,000 mg/day Pemphigus vulgaris and assciated cnditins* 35 t 45 mg/kg/day PO r 1 g PO BID 50 mg/week DM/PM: 3 g/day PV, etc: 2 g/day Page 11 f 28

12 Drug Name Dsing Regimen Dse Limit/ Maximum Dse tacrlimus (Prgraf ) Systemic crticsterids (e.g., prednisne, prednislne, methylprednislne) Dermatmysitis/Plymysitis* 0.075mg/kg/day PO BID OR begin at 1 mg PO BID, increase t reach trugh f 5-10 ng/ml An equivalent dse f prednisne 1 mg/kg/day (with r withut tapering) 2 mg/kg/day Disease-mdifying therapies fr relapsing remitting MS Aubagi (teriflunmide) 7 r 14 mg PO QD 14 mg/day Avnex, Rebif (interfern beta-1a) Avnex: 30 mcg IM Q week Rebif: 22 mcg r 44 mcg SC TIW Avnex: 30 mcg/week Betasern, Extavia (interfern beta-1b) glatiramer acetate (Cpaxne, Glatpa ) Rebif: 44 mcg TIW 250 mcg SC QOD 250 mg QOD Cpaxne: 20 mg SC QD r 40 mg SC TIW Glatpa: 20 mg SC QD Cpaxne: 20 mg/day r 40 mg TIW Glatpa: 20 mg/day Gilenya (finglimd) 0.5 mg PO QD 0.5 mg/day Lemtrada See regimen (alemtuzumab) Nvantrne (mitxantrne) Ocrevus TM (creliuzmab) IV infusin fr 2 treatment curses: First curse: 12 mg/day n 5 cnsecutive days Secnd curse: 12 mg/day n 3 cnsecutive days 12 mnths after first curse 12 mg/m 2 given as a shrt (apprximately 5 t 15 minutes) IV every 3 mnths Initial: 300 mg IV, then 300 mg IV 2 weeks later Maintenance: 600 mg IV every 6 mnths Cumulative lifetime dse f 140 mg/m mg/6 mnths Plegridy (peginterfern 125 mcg SC Q2 weeks 125 mcg/2 weeks beta-1a) Tecfidera (dimethyl 120 mg PO BID fr 7 days, fllwed by mg/day fumarate) mg PO BID Tysabri (natalizumab) 300 mg IV every 4 weeks 300 mg/4 weeks Zinbryta (daclizumab) 150 mg SC nce mnthly 150 mg/mnth Therapeutic alternatives are listed as Brand name (generic) when the drug is available by brand name nly and generic (Brand name ) when the drug is available by bth brand and generic. *Off-label Appendix C: Cntraindicatins Appendix D: General Infrmatin CLL: These patients have a pattern f infectin caused by encapsulated bacteria (Haemphilus influenzae, pneumccci, streptccci) which tends t be chrnic and/r recurrent and des nt demnstrate imprvement with an adequate curse f PO antibitics and/r prphylactic antibitics. Recurrent infectins may include sinus infectins, titis media, brnchiectasis and pygenic pneumnias. Dermatmysitis, plymysitis: IVIG may be medically necessary after less than 4 mnths trial f prednisne r prednisne cmbinatin therapies if the patient has prfund, rapidly prgressive and/r ptentially life threatening muscular weakness (e.g., life-threatening aggressive disease with invlvement f Page 12 f 28

13 respiratry musculature, pssibly requiring hspitalizatin, elective intubatin and mechanical ventilatry supprt) and is refractry t r intlerant f previus therapy. Failure r clinically significant adverse effects t cntinual high dse sterids in cmbinatin with ther immunsuppressive agents is defined as the patient being unrespnsive r prly respnsive t therapy (persistently elevated serum creatine kinase (CK) levels and/r lack f imprvement n muscle strength imprvement scales) r intlerant f therapy (i.e., sterid mypathy r severe steprsis). Inclusin bdy mysitis (IBM) is classified as ne f the idipathic inflammatry mypathies. Hwever, despite sme histlgic similarities, the clinical manifestatins, treatment and prgnsis are different frm DM and PM. IBM is relatively resistant t standard immunsuppressive therapy. In tw clinical studies, IVIG was unable demnstrate bjective imprvement in the treatment f IBM. ITP: Definitins f acute vs. chrnic ITP: Per an Internatinal Wrking Grup cnsensus panel f ITP experts, ITP is defined as newly diagnsed (diagnsis t 3 mnths), persistent (3 t 12 mnths frm diagnsis), r chrnic (lasting fr mre than 12 mnths). Althugh nt frmally validated, these definitins are supprted and used by the American Sciety f Hematlgy (ASH). In clinical trials evaluating the efficacy and safety f IVIG in ITP, acute ITP was defined as cnditin duratin f up t 6 mnths while chrnic ITP was defined as cnditin duratin f greater than 12 mnths. Per the 2011 ASH guidelines, respnse t treatment was defined by the fllwing: A respnse wuld be defined as a platelet cunt 30,000/µL and a greater than 2-fld increase in platelet cunt frm baseline measured n 2 ccasins > 7 days apart and the absence f bleeding. A failure wuld be defined as a platelet cunt < 30,000/µL r a less than 2-fld increase in platelet cunt frm baseline r the presence f bleeding. Platelet cunt must be measured n 2 ccasins mre than a day apart. There have been reprts f fatal intravascular hemlysis with Rh(D) immune glbulin and specific mnitring is required. This therapy is nt necessarily recmmended ver IVIG but can be used instead in patients wh are Rh psitive, have a negative direct antiglbulin test (DAT), and have nt had a splenectmy. Fr acute ITP, a single dse f IVIG is used as first line treatment. Fr adults, a secnd dse may be given if necessary. (Acute) inflammatry demyelinating plyneurpathy r GBS: GBS subtypes include the fllwing: acute inflammatry demyelinating plyneurpathy (AIDP), acute mtr axnal neurpathy (AMAN), acute mtr-sensry axnal neurpathy (AMSAN), and Miller Fisher syndrme (MFS). Miller Fisher syndrme is a rare, acute plyneurpathy characterized by ataxia (abnrmal muscle crdinatin), phthalmplegia (paralysis f the eye muscles), and areflexia (absence f the reflexes). Elevated CSF prtein, with a nrmal CSF white bld cell cunt, is ften present; fifty t 66 percent the first week f symptms and 75 percent the third week. GBS and AIDP typically prgresses ver 2 weeks, and the majrity f patients achieve nadir f the disease by fur weeks. Initiatin f IVIG within 2 weeks f symptm nset appears t be as effective as plasma exchange (PE). The cmbinatin f IVIG and plasmaphresis used tgether is nt better than either treatment used alne. The cmbinatin f IVIG and IV methylprednislne was nt mre effective than IVIG alne. Immunabsrptin is an alternative technique t PE that remves immunglbulins. There is insufficient evidence t recmmend the use f immunabsrptin fr GBS. CSF filtratin is as effective as PE fr treatment f GBS. Pulmnary functin risk factrs include ne r mre f the fllwing: Frced vital capacity < 20 ml/kg Page 13 f 28

14 Maximal inspiratry pressure < 30 cm H2O Maximal inspiratry pressure < 40 cm H2O 30% reductin in vital capacity frm baseline (Chrnic) inflammatry demyelinating plyneurpathy r CIDP: The definitin f CIDP includes multifcal acquired demyelinating sensry and mtr neurpathy (MADSAM) variant r when sensry CIDP exists with ther causes f neurpathy such as diabetes and Charct-Marie-Tth (CMT), as evidenced by superimpsed features f CIDP. IVIG, crticsterids, and plasmapheresis are all cnsidered first-line treatments fr patients with mderate t severe disability. Patient-specific factrs may determine the apprpriate chice f therapy. As evidence f prgressin is mre significant than the level f disability, mild cases f CIDP may nt need t be treated aggressively if they are stable, but any signs f prgressin warrants effective treatment with IVIG t begin immediately. Plasmapheresis has nt been shwn t be mre effective than IVIG, hwever, it may be used in patients wh are unrespnsive t bth IVIG and crticsterid therapy. Kawasaki: The efficacy f intravenus immunglbulin (IVIG) administered in the acute phase f Kawasaki disease in reducing the prevalence f crnary artery abnrmalities is wellestablished. The mechanism f actin f IVIG in treating Kawasaki disease is unknwn; hwever IVIG appears t have a generalized anti-inflammatry effect. Fr patients with persistent r recurrent fever after initial IVIG infusin, IVIG retreatment may be useful. Failure t respnd usually is defined as persistent r recrudescent fever 36 hurs after cmpletin f the initial IVIG infusin. Mst experts recmmend retreatment with IVIG, 2 g/kg. The putative dse-respnse effect f IVIG frms the theretical basis fr this apprach. Kidney transplant: MMN: MM: The cmbinatin f intravenus immunglbulin (IVIG) and Rituxan (rituximab) fr desensitizatin prir t renal transplantatin is cnsidered investigatinal at this time. Larger, prspective, randmized cntrlled trials are needed t evaluate the lng-term efficacy and safety f this treatment and t cmpare this prtcl with the current treatment f IVIG alne. In a retrspective analysis f 50 kidney transplant patients at Jhns Hpkins Hspital, all patients were live dnr HLA incmpatible recipients. Desensitizatin included plasmapheresis with lw dse IVIG, mycphenlate and tacrlimus, and intraperative inductin therapy with anti-il2 receptr antibdies. Twenty five f the higher risk patients als received rituximab (375 mg/m 2 ) the day prir t transplant. There was n significant difference in the incidence f acute rejectin within the first 3 mnths f transplant between the tw grups. Further randmized, cntrlled trials are still needed. Althugh nt required fr diagnsis, the presence f a high titer (> 1:1000) f serum Immunglbulin M (IgM) antibdy directed against gangliside-mndialic acid (IgM Anti- GM1 antibdies) prvides independent supprt fr MMN (> 80% f patients). Althugh n reprts exist f cntrlled trials f immunsuppressive drugs in patients with multifcal mtr neurpathy, there are a series f anecdtal reprts f patients wh transiently respnded t ral r pulsed dses f cyclphsphamide, hwever, this treatment was assciated with significant side effects, related in part t the cumulative dse f cyclphsphamide. Plateau phase is defined as the time when ther causative rganisms that may be present due t dysfunctin in ther immunlgic cells besides the B-cell lines f defense are less likely t be present. IVIG in any ther phase is cnsidered nt medically necessary. These patients have a pattern f infectin caused by encapsulated bacteria (Haemphilus influenzae, pneumccci, streptccci) which tends t be chrnic and/r recurrent and des nt demnstrate imprvement with an adequate curse f PO antibitics and/r prphylactic antibitics. Recurrent infectins may include sinus infectins, titis media, brnchiectasis and pygenic pneumnias. Page 14 f 28

15 MS: The clinical curse f MS usually falls within ne f the fllwing categries, with the ptential fr prgressin frm ne pattern t a mre serius ne: Relapsing-remitting MS: This frm f MS is characterized by clearly defined acute attacks with full recvery r with sme remaining neurlgical signs/symptms and residual deficit upn recvery. The perids between disease relapses are characterized by a lack f disease prgressin. Secndary prgressive MS: The disease begins with an initial relapsing-remitting curse, fllwed by prgressin at a variable rate that may als include ccasinal relapses and minr remissins. Prgressive-relapsing MS: Persns with prgressive-relapsing MS experience prgressive disease frm nset, with clear, acute relapses that may r may nt reslve with full recvery. Unlike relapsing-remitting MS, the perids between relapses are characterized by cntinuing disease prgressin. Primary prgressive MS: The disease shws gradual prgressin f disability frm its nset, withut plateaus r remissins r with ccasinal plateaus and temprary minr imprvements. MG: Myasthenia gravis (MG) is a disrder f neurmuscular functin that is characterized by fatigue and weakness f the muscular system withut atrphy r sensry deficits. Myasthenia crisis refers t exacerbatin sufficient t endanger life, and usually invlves respiratry failure in MG, therefre wuld nt include disabled patients wh are able t walk with r withut assistance. Intravenus Immunglbulin (IVIG) has nt been shwn t be superir t plasmapheresis in the treatment f life-threatening myasthenia gravis. High-dse IVIG may temprarily mdify the immune system and suppress autantibdy prductin t imprve severe myasthenia gravis symptms. The effect f IVIG is seen typically in less than a week, and the benefit can last fr three t six weeks. IVIG is used t quickly reverse an exacerbatin f myasthenia. Accrding t the Eurpean Federatin f Neurlgical Studies (EFNS) guidelines n the use f intravenus immunglbulin in treatment f neurlgical diseases, the efficacy f IVIG has been prven acute exacerbatins f myasthenia gravis and shrt-term treatment f severe MG (level A recmmendatin). A small clinical trial cnducted by Wegner and Ahmed shwed that lng-term IVIG was effective. This trial included six patients wh were anti-achr-ab-psitive. These patients received IVIG at a dsage f 400 mg/kg/day fr 5 days then a maintenance therapy f 400 mg/kg fr 1 day every 3 t 4 mnths. After a 2 year fllw up, all patients maintained a gd functinal status and side effects frm IVIG did nt increase. NAIT: NAIT is caused by maternal allantibdies directed against fetal (paternally inherited) platelet antigens as a result f fet-maternal transplacental passage f incmpatible platelets during pregnancy. HPA-1a is the platelet-specific antigen implicated in mst cases f nenatal allimmune thrmbcytpenia. Administering IVIG t the mther during pregnancy is the mst successful strategy fr increasing the fetal platelet cunt and has becme the recmmended standard treatment f knwn fetal allimmune thrmbcytpenia. Studies have shwn that weekly infusins (1 g/kg maternal bdy weight) beginning at 20 t 24 weeks' gestatin stabilize r increase the fetal platelet cunt in fetuses with dcumented allimmune thrmbcytpenia. In very high-risk pregnancies (intracranial hemrrhage in a previus sibling befre 30 weeks' gestatin), sme investigatrs recmmend starting IVIG therapy as early as 12 t 14 weeks' gestatin. Page 15 f 28

16 Althugh the mechanism f actin f IVIG in FAIT is nt clearly defined, it is pstulated that IVIG decreases maternal allantibdies and may als blck transplacental transprt f maternal antiplatelet antibdies. There is still n cnsensus n the ptimal prtcl fr managing IVIG after it is begun. Paraneplastic syndrmes: Paraneplastic syndrmes are the remte effects f a cancer unrelated t the effects f the tumr r its metastasis. Smetimes they are assciated with lw immune glbulin values and smetimes they are assciated with autantibdies. The cmbinatin f IVIG, cyclphsphamide, and methylprednislne in patients with paraneplastic cerebellar degeneratin and antineurnal antibdies in is nt effective. Anti-NMDA encephalitis Althugh n standard f care fr anti-nmda encephalitis exists, n the basis f data frm the reviews cmpleted, cncurrent IVIG (0.4 g/kg per day fr 5 days) and methylprednislne (1 g/day fr 5 days) is preferred ver plasma exchange. If n respnse is seen after 10 days, a secnd-line therapy is started. Althugh there is a paucity f randmized cntrlled and cmparative trials regarding the use f IVIG fr this disrder, because f the severity f anti-nmda encephalitis and n the basis f data frm the cmpleted reviews and case series, it has been nted that individuals wh received early tumr treatment (usually with immuntherapy) had better utcme and fewer neurlgical relapses than the rest f the patients, IVIG given cncurrently with crticsterids has been determined t assist with full r substantial recvery in apprximately 75% f the individuals with anti-nmda encephalitis. Opsclnus-myclnus-syndrme r "dancing eyes-dancing feet" syndrme is a rare neurlgical disrder that affects infants and yung children and has been described in adult patients with cancer The current therapeutic strategies fr OMS prvide a brad spectrum f nnselective immuntherapies, including nncyttxic and cyttxic drugs, intravenus immunglbulins, ACTH and plasma exchange Intravenus immunglbulin G is ccasinally used as an alternative t ACTH. Altgether, the available evidence suggests that IVIG may be an effective treatment in parainfectius and idipathic OMS. Treatment with IVIG has been reprted in a few idipathic adult-nset OMS cases in literature and they have cncluded that idipathic OMS presents an age dependent prgnsis and immuntherapy. IVIG seems t be assciated with a faster recvery. Trends in the standard f care f OMS reprt that ACTH, prednisne, and intravenus immunglbulin were used with equal frequency, but ACTH was assciated with the best early respnse Parvvirus B19 infectin: Human parvvirus B19 infectin can give rise t the lss f mature red bld cells, severe anemia and the frmatin f immune cmplexes. A rbust antibdy respnse is necessary fr virus clearance and cntrl f the infectin. IVIG has been shwn t be effective in recurrent infectin in augmenting the inadequate humral immune respnse. Based n the evidence available, IVIG therapy has becme the standard f care if the aplastic crisis becmes prlnged, even thugh there are n definitive clinical trials demnstrating the efficacy f HPV B19-induced anemia. Use f IVIG fr treatment in parvvirus B19 infectin is a categry 2A NCCN recmmendatin IVIG dse adjustments: Adjustment f the IVIG dse and time interval between dses shuld be based n trugh levels measured every mnth fr the first three mnths f therapy and again at six mnths Adjustments t infusin rates and measuring f serum IgG levels may be needed during infectins r in persns wh have a high catablism f infused IgG Page 16 f 28

17 T reduce infectin frequency in immundeficient patients, serum trugh levels shuld be maintained at mg/dl, a value clse t the lwer limit f nrmal. All IgG trugh levels utside f the lw nrmal range f mg/dl require dsage adjustment. Pemphigus vulgaris and related cnditins: IVIG therapy fr pemphigus vulgaris must be used nly fr shrt-term therapy and nt as a maintenance therapy. IVIG dse adjustments: Adjustment f the IVIG dse and time interval between dses shuld be based n trugh levels measured every mnth fr the first three mnths f therapy and again at six mnths Adjustments t infusin rates and measuring f serum (immunglbulin G) IgG levels may be needed during infectins r in persns wh have a high catablism f infused IgG T reduce infectin frequency in immundeficient patients, serum trugh levels shuld be maintained at mg/dl, a value clse t the lwer limit f nrmal. All IgG trugh levels utside f the lw nrmal range f mg/dl require dsage adjustment. Fr pemphigus vulgaris, pemphigus fliaceus, bullus pemphigid, mucus membrane pemphigid (a.k.a. cicatricial pemphigid), epidermlysis bullsa acquisita: the treatment is cnsidered cmplete when the patient is free f disease after a 16-week interval between the last tw infusin cycles; Examples f clinically significant adverse effects t crticsterids, immunsuppressive agents (e.g., cyclphsphamide, azathiprine, mycphenlate mfetil) are diabetes r fractures frm chrnic sterid use. PI: Black bx warning: Thrmbsis, renal dysfunctin, acute renal failure, smtic nephrsis, and death may ccur. Cmmn variable immundeficiency (CVID), the mst frequently diagnsed primary immundeficiency, is characterized by a lw serum IgG level antibdy deficiency at least 2 SDs belw the mean fr age, with mst patients having cncurrent deficiencies f IgA and IgM. Many Patients with CVID have IgG levels belw 639 that require IVIG. Hwever, there are rare instances when a patient will have nrmal IgG levels. The serum immunglbulin measurement alne des nt establish a diagnsis f CVID. A definitive diagnsis f CVID is established when a patient des nt demnstrate a prlnged antibdy respnse t immunizatin with prtein antigens (e.g., tetanus) r carbhydrate antigens (e.g., pneumcccal capsular plysaccharides such as pneumvax). The gamma glbulin band cnsists f 5 immunglbulins: abut 80% immunglbulin G (IgG), 15% immunglbulin A (IgA), 5% immunglbulin M (IgM), 0.2% immunglbulin D (IgD), and a trace f immunglbulin E (IgE). The use f intravenus immune glbulin shuld be reserved fr patients with serius defects f antibdy functin. All immune deficiency cnditins require nging mnitring f the patient s clinical cnditin with measurement f pre-infusin (trugh) serum IgG levels. Fr lifelng treatment serum trugh IgG levels shuld be measured befre the infusin, and then mnitred every 3 mnths t maintain lw nrmal level (usually mg/dl). See Appendix E: Reference Ranges fr Immune Glbulin Levels. Stiff persn syndrme: Paraneplastic stiff-man syndrme (als knwn as Mersch-Wltmann syndrme) is a rare prgressive neurlgical disrder characterized by prgressive rigidity and stiffness f the axial musculature, assciated with painful spasms, primarily in the lwer limbs, neck and trunk. Symptms are related t autantibdies directed against glutamic acid decarbxylase in the nervus system called anti-gad antibdies. This antibdy marker, which is an antibdy t an enzyme fund bth in the pancreas and in nerve tissue, is fund in high cncentratins in classical Stiff-man syndrme. In mst cases, imprvement in symptms ccurs with cmbinatins f diazepam and baclfen, ften in reasnably high dsage. Where all drug treatments fail t give sufficient Page 17 f 28

18 relief frm spasms and pain, treatment is directed against the underlying immunlgic cnditin with drug chices cnsisting f sterids (either intravenus r rally), plasma exchange r pled IVIG. Current treatments d nt ffer r lead t a cure. Hwever, they are able t cntrl symptms in the majrity f patients. Appendix E: Reference Ranges fr Immune Glbulin Levels The May Clinic suggests the fllwing reference ranges f immune glbulins: Age IgG IgA IgM 0 t < 5 mnths mg/dl 7-37 mg/dl mg/dl 5 t < 9 mnths mg/dl mg/dl mg/dl 9 t < 15 mnths mg/dl mg/dl mg/dl 15 t < 24 mnths 313-1,170 mg/dl mg/dl mg/dl 2 t < 4 years 295-1,156 mg/dl mg/dl mg/dl 4 t < 7 years 386-1,470 mg/dl mg/dl mg/dl 7 t < 10 years 462-1,682 mg/dl mg/dl mg/dl 10 t < 13 years 503-1,719 mg/dl mg/dl mg/dl 13 t < 16 years 509-1,580 mg/dl mg/dl mg/dl 16 t < 18 years 487-1,327 mg/dl mg/dl mg/dl 18 years 767-1,590 mg/dl mg/dl mg/dl V. Dsage and Administratin Refer t full prescribing infrmatin fr specific dsage instructins. Dsage must be individualized and is highly variable depending n the nature and severity f the disease and n the individual patient respnse (e.g., serum IgG trugh levels). There is n abslute maximum dsage f immune glbulin r hyalurnidase. Drug Name Indicatin Dsing Regimen Maximum Dse Bivigam PI Initial: 300 t 800 mg/kg IV every 3 t 4 weeks Maintenance: IV: given every 3 t 4 weeks with dse adjusted per serum IgG level and clinical respnse Carimune NF ITP Initial: 0.4 g/kg IV QD cnsecutively n days 2 t 5 PI Initial: 0.4 t 0.8 g/kg IV every 3 t 4 weeks Maintenance: IV: given every 3 t 4 weeks with dse adjusted per serum IgG level and clinical respnse Cuvitru PI Initial: Previus IGIV/HyQvia dse in grams divided by number f weeks between IV dses and multiplied by Give SC at regular intervals QD t every 2 weeks beginning 1 week after last IV r HyQvia dse Flebgamma 5% PI Initial: 300 t 600 mg/kg IV every 3 t 4 weeks Maintenance: Page 18 f 28

19 Drug Name Indicatin Dsing Regimen Maximum Dse IV: given every 3 t 4 weeks with dse adjusted per serum IgG level and clinical respnse Flebgamma 10% ITP 1 g/kg IV QD fr 2 cnsecutive days PI Initial: 300 t 600 mg/kg IV every 3 t 4 weeks Gamastan S/D Gammagard Liquid Hepatitis A prphylaxis Measles pstexpsure prphylaxis Rubella pstexpsure prphylaxis Varicella pstexpsure prphylaxis Maintenance: IV: given every 3 t 4 weeks with dse adjusted per serum IgG level and clinical respnse Husehld and institutinal case cntacts: 0.1 ml/kg IM nce Travel t Hepatitis A-endemic areas: Up t 1 mnth stay: 0.1 ml/kg IM nce Up t 2 mnths stay: 0.2 ml/kg IM nce 2 mnths r lnger stay: 0.2 ml/kg IM every 2 mnths 0.1 ml/kg as a single dse r 0.2 ml/kg every 2 mnths 0.25 ml/kg IM nce 0.25 ml/kg 0.55 ml/kg IM nce 0.55 ml/kg 0.6 t 1.2 ml/kg IM nce 1.2 ml/kg MMN 0.5 t 2.4 g/kg/mnth IV PI Initial: IV: 300 t 600 mg/kg every 3 t 4 weeks SC: Previus IGIV dse in grams divided by number f weeks between IV dses and multiplied by 1.37 Maintenance: IV: given every 3 t 4 weeks with dse adjusted per serum IgG level and clinical respnse Gammagard S/D Less IgA SC: given nce weekly with dse adjusted per PI CLL 400 mg/kg IV every 3 t 4 weeks ITP KS PI 1 g/kg IV, up t 3 dses n alternate days 1 g/kg IV single dse r 400 mg/kg IV QD fr fur cnsecutive days Initial: IV: 300 t 600 mg/kg every 3 t 4 weeks Page 19 f 28