SCPS Specialty Pharmacy Protocols (CDTM Services Module)

Transcription

1 SCPS Specialty Pharmacy Protocols (CDTM Services Module) Overview and Pharmacy s Role UAN: H01-P Launch: Expires:

2 Disclosure AnhMinh (Mindy) Ta, PharmD, BCPS, Staffing Resource Network Pharmacist and Albert Rizos, PharmD, BCPS, Manager, System Clinical Pharmacy Services have no relevant financial disclosures.

3 Disclaimer Medications Managed by SHC Specialty Pharmacy This presentation is mainly focused on injectable medications administered by the clinic or self administered by clinic s patients for treatment of the listed diseases per protocol. Please refer to the protocols and practice guidelines for more detail. A copy of all protocols and other related resources can be found on the SharpNet P&P website. Rheumatoid Arthritis Osteoporosis Psoriasis/Psoriatic Arthritis Inflammatory Bowel Disease Multiple Sclerosis Ankylosing Spondylitis Hepatitis C

4 Objectives Upon completion of this course, you will be able to successfully: List the Specialty Pharmacy disease state protocols and where they are found and maintained State the basis for the disease state protocols, i.e., major guidelines as relevant Describe the overall approach to the use of biologics managed by Specialty Pharmacy, e.g., find and apply biologic selection, dosing guidance, special population considerations, and prevention of serious potential adverse events Describe one key pharmacotherapy practice pearl specific to each disease state Explain two key patient education pearls specific to each disease state (this may not be unique to a disease, i.e., may be common to several) Explain the SCPS Specialty Pharmacy CDTM workflow, e.g., location and use of the Initial Assessment Form for each disease or drug, documentation, communication to other clinicians, patient education, ordering

5 Pharmacist Comprehensive Drug Therapy Management Protocols Medications Managed by Specialty Pharmacy Collaborative Drug Therapy Management through Medication Therapy Protocols TNFi FDA Preg FDA REMS Actemra tocilizumab C Y Y RA Ankylosin g Spondyliti s Psoriasis, Psoriatic Arthritis Avonex Interferon beta 1a C Y Betaseron Interferon beta 1b C Y Cimzia certolizumab Y B** Y Y Y Y Copaxone glatiramer acetate Cosentyx secukinumab B Y Enbrel etanercept Y B Y Y Y B Extavia Interferon beta 1b C Y IBD MS Osteoporosis Forteo teriparatide C Y Y Humira adilimumab Y B Y Y Y Y Orencia abatecpt C Y Prolia denosumab X Y Y Rebif Interferon beta 1a C Y Simponi golimumab Y B Y + MTX Y Y Y Stelara ustekinumab B Y Y *Combo therapy with Ribavirin (Copegus, Rebetol) ** Y

6 Pharmacist Comprehensive Drug Therapy Management Protocols RHEUMATOID ARTHRITIS Medications Managed by Specialty Pharmacy Collaborative Drug Therapy Management through Medication Therapy Protocols TNFi FDA Preg FDA REMS RA Ankylosing Spondylitis Psoriasis, Psoriatic Arthritis Actemra tocilizumab C Y Y Avonex Interferon beta 1a C Y Betaseron Interferon beta 1b C Y Cimzia certolizumab Y B** Y Y Y Y Copaxone glatiramer acetate B Y IBD MS HCV Osteoporosis Cosentyx secukinumab B Y Enbrel etanercept Y B Y Y Y Extavia Interferon beta 1b C Y Forteo teriparatide C Y Y Humira adilimumab Y B Y Y Y Y Orencia abatecpt C Y Pegasys Peg-interferon alfa-2a* X Y Peg-Intron Peg-interferon alfa-2b* X Y Prolia denosumab X Y Y Rebif Interferon beta 1a C Y Simponi golimumab Y B Y + MTX Y Y Y Stelara ustekinumab B Y Y *Combo therapy with Ribavirin (Copegus, Rebetol) **

7 Assessment Process for Rheumatoid Arthritis The specialty pharmacist will review the following with the patients*: 1. Medication profile (both Rx, OTC, supplements) 2. Significant drug-drug interactions (DDI) Rule out significant DDI: Abatacept (Orencia), anakinra (Kineret), rituximab (Rituxan), Natalizumab (Tysabri), Cyclophosphamide 3. Allergy profile (drug and non-drug) and document reaction Caution for latex allergy: golimumab (Simponi) 4. Medical History (contraindication or concerning to given intended therapy) History of TB: inquire about any history of positive PPD or any type of exposure (even with recent negative PPD) History of fungal infection: Cocci test Hepatitis, multiple sclerosis, Guillain-Barre syndrome, heart failure, pregnancy or planning to become pregnant 5. Physical or functional limitations that would impact self- injection of therapy If limitation is present, ascertain whether there will be a caregiver and train that person when necessary 6. Train for administration technique (Pre-filled Syringe or Pen) 7. Educate patients of side effect profile Medication guide provided to patients as applicable 8. Disease state history & symptom assessment 9. Discuss medication storage and disposal (i.e. provision of Sharps Containers) 10. Refill process: Including follow up assessments and delivery of subsequent medication *See protocol assessment form for more detail

8 Rheumatoid Arthritis (RA) Pathophysiology and Clinical Presentation Pathophysiology Clinical Presentation Rheumatoid factor (RF) + Chronic inflammation of the synovium Elevated sedimentation rate (ESR) + Joint pain, morning stiffness, involve multiple joints C-Reactive protein + Normally symmetrical Anti-cyclic citrullinated peptide antibodies +

9 Rheumatoid Arthritis (RA) Non-biologic DMARDs to Treat RA Medication Dose Adverse Effects Comments Methotrexate (MTX) Hydroxychroroquine (HCQ) Leflunomide (LEF) mg PO ONCE WEEKLY (up to 20-30mg weekly); may divide weekly dose into 2 doses every 12 hours ONE DAY of the week mg weekly IM or SC *caution in hepatic & renal impairment. - CrCl < 50ml/min: dose 50% mg PO BID *Adjust for renal dysfunction 100mg PO daily x 3 days, THEN 20mg daily *Not recommended for pre-existing liver disease N/V, stomatitis, thrombocytopenia, increase LFTs, chronic hepatotoxicity, photosensitivity GI complaints, skin reaction, headaches, retinal damage (rare) GI complains, reversible alopecia, rash, elevated transaminases, peripheral neuropathy Non-biologic DMARD of choice! Bioavailability with oral doses exceeding 7.5mg Monitor myelosuppression, liver dysfunction, pulmonary fibrosis *teratogenic AVOID in Pregnancy Low toxicity but moderate clinical effect. *Routinely monitor for ocular toxicity Equivalent to MTX: can alternate with MTX if patient can t tolerate MTX *teratogenic AVOID in Pregnancy Minocycline 100mg PO BID - CrCL< 80ml/min: max 200mg daily *caution in hepatic & renal impairment N/V, anorexia, hepatotoxicity Moderate reduction in RA progression compared with other non-biologics Sulfasalazine mg PO daily, titrate to 1000mg PO BID Headache, rash, gastric distress, myelosuppression, increase LFTs May be used monotherapy or as part of combination Adapted from Burke RA, White ND, DMARDs Disease Modifying Anti-Rheumatic Drug; LFT liver function test; GI gastrointestinal; IM intramuscular; SC - subcutaneous

10 Rheumatoid Arthritis (RA) Biologic DMARDs to Treat RA: Medications Managed by SHC Specialty Pharmacy CLASS MEDICATION DOSE FREQUENCY Comments Common Side Effect TNF-α Inhibitor - AVOID in pts with NYHA class III-IV heart failure - Vaccination and TB screening MUST be done prior to therapy initiation - Monitor for infection Adalimumab (Humira) Certolizumab (Cimzia) Etanercept (Enbrel) 40mg SC 400mg SC, THEN 200mg SC 50mg SC, 25mg SC Every 14 days, may to 40mg weekly in pts not taking MTX 400mg SC week 0, 2 and 4 THEN 200mg SC every 2 weeks Weekly or twice weekly *better response when combine with MTX *better response when combine with MTX *better response when combine with MTX *Recommended for patients with treated Hepatitis C (Child-Pugh class A) Headache, sinus infections, rash, nausea Upper respiratory infections (flu, cold), rash, urinary tract infections (bladder infections) Headache, sinus infections. T-Cell co-stimulation modulator IL-6 Receptor antagonist - Monitor for infection Golimumab (Simponi) Abatacept (Orencia) Tocilizumab (Actemra) 50mg SC Monthly with MTX CI: Latex allergy Sinus infections, rash 125mg SC Weekly May be useful in those who are not responsive to TNFi 162mg SC >100kg SC weekly <100mg SC every other week, may per response Indicated for patients who have not responded to TNFi Headache, sinus infections, sore throat, nausea Increased cholesterol possibly requiring treatment DMARDs Disease Modifying Anti-Rheumatic Drug; TNFi (TNF-α Inhibitor) anti-tumor necrosis factor

11 Rheumatoid Arthritis (RA) Recommendation on the Treatment of Early RA 2 EARLY RA (Disease duration 6 months) SHC Specialty pharmacy DMARD monotherapy Target: Low disease activity or remission Combination DMARD* or Biologics +/- MTX* Moderate or high Disease Activity *consider low-dose glucocorticoids (<10mg/d) in patients with moderate or high disease activity and short term glucocorticoid (<3 month) for disease flare Moderate or high Disease Activity See ESTABLISHED RA algorithm Adapted from ACR: RA treatment guideline 2 Biologics = TNFi or non-tnfi; TNFi anti-tumor necrosis factor; *NOTE: highlight area(s) indicates Specialty Pharmacy involvement.

12 Rheumatoid Arthritis (RA) Recommendation on the Treatment of Established RA 2 ESTABLISHED RA (Disease duration 6 months) *consider low-dose glucocorticoids (<10mg/d) in patients with moderate or high disease activity and short term glucocorticoid (<3 month) for disease flare Target: Low disease activity or remission DMARD monotherapy Moderate or high Disease Activity* Combination DMARD* or Biologics +/- MTX* or Tofacitinib +/- MTX Moderate or high Disease Activity* Single TNFi failure Single non-tnfi failure Non-TNF Biologic +/- MTX or TNFi +/- MTX Another non-tnf Biologic +/- MTX Moderate or high Disease Activity* Low Disease activity, but not remission, continue treatment In remission, consider tapering treatment Do NOT discontinue all RA treatment Dual failure: TNFi & non TNFi failure Moderate or high Disease Activity* Multiple TNFi failure Multiple non-tnfi failure Another non-tnf Biologic +/- MTX or Tofacitinib +/- MTX Non-TNF Biologic +/- MTX or Tofacitinib +/- MTX TNF Biologic +/- MTX (in TNFi naïve) or Tofacitinib +/- MTX Adapted from ACR: RA treatment guideline 2 *NOTE: highlight area(s) indicates Specialty Pharmacy involvement. TNFi anti-tumor necrosis factor

13 Rheumatoid Arthritis (RA) Step Down vs. Traditional Step Up Approach to Treatment STEP DOWN APPROACH Use of combination therapy (double/triple) or biologic DMARD as initial treatment 3,6 Aggressively control disease progress, low disease activity or remission is achieved quickly Once goal achieve, gradually reduce/stop most toxic/expensive medications TRADITIONAL APPROACH Starting treatment with monotherapy and add subsequent DMARDs if adequate efficacy is not achieved Risk of irreversible joint damage Lower change of achieving remission later on Therapy goal: patient can remain in remission without TNFi

14 Rheumatoid Arthritis (RA) Patient case R.A. has been doing well with MTX and sulfasalazine therapy until 2 months ago; she started to experience pain and warmth in the joints and stiffness in the morning. Today, pharmacy got a referral from a physician to monitor the patient on Simponi. Medications profile: Pantoprazole 40 mg daily Metformin 850 mg twice daily Levothyroxine 100 mcg daily Naproxen 500 mg twice daily Golimumab (Simponi) 50mg SC monthly Labs: Reumatoid factor (-) Anti cyclic citrullinated peptides (-) Bone erosion by radiography (+) Which would be the most appropriate action at this time? A. Recommend to change Simponi to 50mg SC weekly B. Discontinue Naproxen C. Change previous MTX dose to 25mg weekly D. Referral to rheumatology to add MTX to medication regimen

15 Rheumatoid Arthritis (RA) Key Points Treatment should be started early Methotrexate dosing (see table slide 8) Dosing is ONCE WEEKLY (NOT daily) or every 12 hour ONE DAY a week Traditional Step Up treatment therapy Non-biologic DMARDs as initial therapy NEWER Step Down treatment therapy, a more aggressive approach Usually TNF-α Inhibitor is selected before other biologics 3 months to evaluate response Biologic DMARDS as initial treatment 6 months to evaluate adequate disease activity response if patient is on a non-tnfi agent Consider dose reduction or tapering after satisfactory response 2,3,6 More effective when used in combination with MTX 1 Adalimumab (Humira), Certolizumab (Cimzia), Etanercept (Enbrel) Must be used in combination with MTX for treatment of RA Golimumab (Simponi) Also Infliximab (Remicade) & Rituximab (Rituxan) not managed by Specialty Pharmacy 17 Latex allergy warning Golimumab (Simponi) - the needle cover on the prefilled syringe and needle cover within auto-injector cap contain dry natural rubber (latex derivative) 17 TNFi (TNF-α Inhibitor) anti-tumor necrosis factor

16 Osteoporosis Treatment Guideline: Initiation of Therapy 4 Hip or Spin fracture BMD T-Score <-2.5 at spine, hip, femoral neck BMD T-Score between -1.0 and -2.5 at spine and femoral neck AND 10 year probably of hip fracture is 3% OR 10 year probability of major osteoporosis-related fracture is 20% based on FRAX* system *Due to inclusion criteria used in the study, FRAX tool is not used in this protocol designed for patients on drug therapy

17 Assessment Process for Osteoporosis The specialty pharmacist will review the following with the patients*: 1. Medication profile(both Rx, OTC, supplements) 2. Significant drug-drug interactions (DDI) Prolia (denosumab): confirm patient is not currently taking Xgena (denosumab) Forteo (Teriparatide): rule out DDI with digoxin (risk of toxicity) 3. Allergy profile (drug and non-drug) and document reaction Confirm patient is NOT allergic to sorbitol (injection ingredient) Prolia contains 4.7% sorbitol Caution for latex allergy: grey needle cap for Prolia pre-filled syringe contains latex derivative & outside of rubber septum for Forteo 4. Medical History (recommendation, precaution and contraindication to given intended therapy) Prolia (denosumab) therapy: Ensure patient is taking recommended Calcium (1000mg) and Vitamin D (400 units) daily History hypoparathyroidism, thyroid surgery or parathyroid surgery (requires clinical monitoring of Ca, Mag, Phos) Contact MD if calcium/mineral abnormalities are unlikely to be corrected orally, i.e., patient is on TPN Pregnancy or planning to become pregnant (contraindicated in patient taking Prolia) Encourage patient to enroll in Amgen s Pregnancy Surveillance Program if become pregnant Poor oral hygiene and invasive dental procedure can contribute to risk of osteonecrosis of the jaw (ONJ) Severe renal impairment risk of hypocalcemia Forteo (Teriparatide) therapy: Lifetime max treatment duration is 2 years History of bone or skeletal cancer 5. Physical or functional limitations that would impact self-injection of therapy (provide training to caregiver when necessary if patient is unable to self-inject) 6. Train for administration technique (Pre-filled Syringe or Pen) 7. Educate patients of side effect profile: medication guide provided to patients as applicable 8. Disease state history, symptom assessment and follow up 9. Discuss medication storage and disposal (i.e. provision of Sharps Containers) & refill process *See protocol assessment form for more detail

18 Pharmacist Comprehensive Drug Therapy Management Protocols OSTEOPOROSIS Medications Managed by Specialty Pharmacy Collaborative Drug Therapy Management through Medication Therapy Protocols TNFi FDA Preg FDA REMS RA Ankylosing Spondylitis Psoriasis, Psoriatic Arthritis Actemra tocilizumab C Y Y Avonex Interferon beta 1a C Y Betaseron Interferon beta 1b C Y Cimzia certolizumab Y B** Y Y Y Y Copaxone glatiramer acetate B Y IBD MS HCV Osteoporosis Cosentyx secukinumab B Y Enbrel etanercept Y B Y Y Y Extavia Interferon beta 1b C Y Forteo teriparatide C Y Y Humira adilimumab Y B Y Y Y Y Orencia abatecpt C Y Pegasys Peg-interferon alfa-2a* X Y Peg-Intron Peg-interferon alfa-2b* X Y Prolia denosumab X Y Y Rebif Interferon beta 1a C Y Simponi golimumab Y B Y Y Y Y Stelara ustekinumab B Y Y *Combo therapy with Ribavirin (Copegus, Rebetol) **

19 Osteoporosis Monitoring Criteria 4 BMD - DXA at baseline Repeat BMD- DXA every 2 years Some patients may require follow-up sooner Accurate height measurement annually Patients who lose 2 cm should have vertebral imaging Medication specific Ca, BUN, Cr before each dose If CrCl <30ml/min, repeat at 7-12 days post dose Use free Ca if available (or Corrected Ca) DXA Image from Blausen gallery 2014

20 Osteoporosis Available Treatment Therapy Therapy Dose Prevention Calcium (carbonate or citrate) mg of elemental Ca Vitamin D I.U daily Treatment: Alendronate (Fosamax) 70mg PO weekly Bisphosphonates Ibandronate (Boniva) 150mg PO monthly; 3mg IV q 3 mon Risedronate (Actonel) Zoledronate acid (Reclast) 35mg PO weekly or 150mg PO monthly 5mg IV yearly rdna origin Teriparatide (Forteo) 20mcg SC daily Hormones (postmenopause) Denosumab (Prolia) Raloxifene (Evista) 60mg SC q 6 mon 60mg PO daily Estradiol, Estropipate, Conj estrogens, Transdermal estradiol, combination of estrogen & progestin Calcitonin Nasal Spray (Miacalcin, Fortical) 200 IU daily, alternate nostrils *See Protocol Appendix for more detail

21 Osteoporosis Medications Managed by Specialty Pharmacy Agent Denosumab (PROLIA) Anti-RANKL IgG2 monoclonal antibody, prevents osteoclast formation Teriparatide (FORTEO) Recombinant parathyroid hormone, increases osteoblast activity Osteoporosis Treatment Indications Postmenopausal with high fracture risk Men with high fracture risk Men with androgen deprivation for nonmetastatic prostate cancer Women with aromatase inhibitors for breast cancer Postmenopausal with high fracture risk Men with high fracture risk Glucocorticoid-induced Dose Frequency 60 mg SC Every 6 months NOTE: grey needle cap on the single-use prefilled syringe contains dry natural rubber (a derivative of latex). 20 mcg SC Daily MAX Life time treatment duration = 2 years Note: Initial administration should be administered when the patient is sitting or lying down, in the event of orthostasis. Dose Adjustment Renal Monitor patients with severe impairment (CrCl <30 ml/minute or on dialysis) due to increased risk of hypocalcemia No dosage adjustment is necessary Hepatic There are no dosage adjustments provided in the manufacturer's labeling (has not been studied) Renal No dosage adjustment necessary Use in severe renal impairment is contraindicated in the Canadian labeling. Hepatic There is no dosage adjustment provided in the manufacturer s labeling (has not been studied) Notes Contraindicated (CI) in hypocalcemia Can exacerbate hypocalcemia Check SrCa before each biannual injection and 7-12 days post-injection in those with a CrCl < 30 ml/minute Must be administered in the clinic or physician s office CI: in pregnancy (inform patient about pregnancy registry) See REMS Medication Guide Osteosarcoma risk. Avoid if a history or active bone cancer, bone metastases, radiation therapy involving the skeleton, hypercalcemia, recent or current urolithiasis Patient self administer injection See REMS Medication Guide regarding osteocarcinoma risk. CI contraindicated * See Protocol Appendix for More Detail

22 Osteoporosis Patient case You got a referral to monitor a patient, who is 60 year old female, on denosumab (Prolia). She has history of T2DM, HTN, CKD. Ht: 60 in Wt: 154 lb (70 kg) Cr: 1.5 (data from medical record 1month ago) Current medications: Lisinopril 5mg daily Furosemide 20mg twice daily Glipizide 5mg twice daily What is the appropriate information the pharmacist must obtain prior to initiating therapy? A. Repeat Serum Cr B. Pregnancy test C. Hgb A1C D. Serum Ca level

23 Osteoporosis Key Points Teraparatide (Forteo) REMS 17 Lifetime therapy 2 years is NOT recommended Denusomab (Prolia) REMS 17 Must correct HYPOcalcemia prior to treatment initiation Especially in patient with CrCl < 30ml/min Pregnancy category X Encourage patient to enroll in Amgen s Pregnancy Surveillance Program if become pregnant Sequential treatment 4 Anabolic (teraparatide) followed by an anti-resorptive (denusomab or bisphosphonate) agent is generally preferred Combined therapy 4 Could be considered in very severe cases (spine & hip fractures)

24 Psoriasis/Psoriatic Arthritis Disease Presentation 5 Affects skin & joint Psoriasis Chronic immune-mediated disease Causes red scaly patches (common) Areas of inflammation and excessive skin production Silvery-white appearance Psoriasis vulgaris (PsV) Most common (80%) Well defined plaque or red raised skin Flaky silvery white buildup of dead skin cell sheds Pain, itching, and cracking Psoriatic Arthritis (PsA) Inflammatory arthropathy associated with psoriasis Correlation with nail involvement Different diagnosis from RA Inflammation and stiffness of soft tissue around the joints Psoriasis skin image from American Academy of Dermatology 5

25 Assessment Process for Psoriasis/Psoriatic Arthritis The specialty pharmacist will review the following with the patients*: 1. Medication profile(both Rx, OTC, supplements) 2. Significant drug-drug interactions 3. Allergy profile (drug and non-drug) and document reaction Caution for latex allergy: golimumab (Simponi), secukinumab (Cosentyx) 4. Medical History (contraindication or concerning to given intended therapy) History of TB: inquire about any history of positive PPD or any type of exposure (even with recent negative PPD) History of fungal infection: Cocci test Hepatitis, multiple sclerosis, Guillain-Barre syndrome, heart failure, pregnancy or planning to become pregnant 5. Physical or functional limitations that would impact self- injection of therapy If limitation is present, ascertain whether there will be a caregiver and train that person when necessary 6. Train for administration technique (Pre-filled Syringe or Pen) 7. Educate patients of side effect profile Medication guide provided to patients as applicable 8. Disease state history & symptom assessment 9. Discuss medication storage and disposal (i.e. provision of Sharps Containers) 10. Refill process: Including follow up assessments and delivery of subsequent medication *See protocol assessment form for more detail

26 Pharmacist Comprehensive Drug Therapy Management Protocols PSORIASIS/PSORIATIC ARTHRITIS Medications Managed by Specialty Pharmacy Collaborative Drug Therapy Management through Medication Therapy Protocols TNFi FDA Preg FDA REMS RA Ankylosing Spondylitis Psoriasis, Psoriatic Arthritis Actemra tocilizumab C Y Y Avonex Interferon beta 1a C Y Betaseron Interferon beta 1b C Y Cimzia certolizumab Y B** Y Y Y Y Copaxone glatiramer acetate B Y IBD MS HCV Osteoporosis Cosentyx secukinumab B Y Enbrel etanercept Y B Y Y Y Extavia Interferon beta 1b C Y Forteo teriparatide C Y Y Humira adilimumab Y B Y Y Y Y Orencia abatecpt C Y Pegasys Peg-interferon alfa-2a* X Y Peg-Intron Peg-interferon alfa-2b* X Y Prolia denosumab X Y Y Rebif Interferon beta 1a C Y Simponi golimumab Y B Y Y Y Y Stelara ustekinumab B Y Y *Combo therapy with Ribavirin (Copegus, Rebetol) **

27 Psoriasis/Psoriatic Arthritis Available Treatments 5 Topical Cream & ointments Phototherapy Systemic Traditional (DMARDs) Methotrexate Cyclosporine Acitretine Leflunomide Sulfasalazine Tacrolimus Azathioprine Mycophenolate Biologics (DMARDs) Adalimumab *Certolizumab **Etanercept *Golimumab Infliximab **Secukinumab Ustekinumab *approved for PsA only **approved for plaque psoriasis only Treatments: Psoriatic Arthritis Mild NSAIDs Intra-articular injections Moderate DMARDs TNFi Severe DMARDs + Biologic DMARDs: Disease Modifying Anti-Rheumatic Drugs; PsA: Psoriatic Arthritis *See protocol appendix for more detail

28 Psoriasis/Psoriatic Arthritis Treatment Algorithm 5 Psoriasis +/- psoriatic arthritis Patient without limited skin disease Should NOT be treated with systemic treatment due to potential risk > benefit 5 YES No *Extensive disease TNFi +/- MTX *Limited disease Topicals/targeted photography UVB Systemic Biologic Lack of effect? Adapted from American Academy of Dermatology 5 *Disease severity is usually measured by the Psoriasis Area and Severity Index (PASI) score NOTE: highlight area(s) indicates Specialty Pharmacy involvement.

29 (I): initial, (M): Maintenanc; Wk: week; PsV: Psorisis vulgaris (plaque); TNFi: TNF-α inhibitor; *See protocol appendix for more detail and APPENDIX for transitioning from one biologic therapy to another Psoriasis/Psoriatic Arthritis Biologic Treatment Agent Indication Dosage Comments Adverse Effects & Dose Adjustment Adalimumab (Humira) (TNFi) Certolizumab (Cimzia) (TNFi)) Etanercept (Enbrel) (TNFi) Golimumab (Simponi) (TNFi) Secukinumab (Cosentyx) IL-17A inhibitor Ustekinumab (Stelara) IL-12/23 Inhibitor Plaque psoriasis: Psoriatic arthritis: Psoriatic arthritis: Plaque psoriasis: Psoriatic arthritis: Plaque psoriasis: Plaque psoriasis Psoriatic arthritis: Adults: (I): 80 mg SC as a single dose (M): 40 mg SC every other week - 1 wk after initial dose 40 mg SC every other week 400 mg SC weeks 0, 2, and 4, followed by 200 mg SC every 2 weeks May consider (M) of 400 mg SC q4wk (2 inj of 200 mg) (I): 50 mg SC twice weekly x 3 months *starting doses of 25 or 50 mg once weekly have also been used successfully (M): 50 mg SC once weekly 50 mg SC once weekly Note: with or without methotrexate. Adults: 300 mg SC once weekly at weeks 0, 1, 2, 3, and 4 followed by 300 mg SC every 4 weeks. *Some patients may only require 150 mg per dose. (I) & (M): 100 kg: 45 mg SC (>100 kg: 90 mg SC) at 0 and 4 wks, and then q 12 wks thereafter. (I) & (M): 45 mg at 0- and 4 weeks, and then every 12 weeks thereafter. Coexistent (Psoriasis & PsA) >100 kg: 90 mg at 0 and 4 weeks, and then every 12 weeks. Note: with or without methotrexate. dose to 40mg every week if in adequate response dose to 2 x 50mg/wk if inadequate response Newer agents - was not included in 2014 consensus recommendation Note: Re-initiation at induction dose if therapy is interrupted. Consider discontinue if still no response after 12 weeks of therapy More effective for PsV Better efficacy in BMI < 25 Dose can to 90mg q 12wk and further to 90mg q 8 wk *TNFi agents are more effective in treating PsA than anti-il *TNFi agents carry a risk of cardiovascular events in severe psoriasis, they might be preferable for treating patients with high BMI and moderate psoriasis. **Infliximab may have increased efficacy against severe cases than do other TNFs or anti-il: - Inadequate respond (loss of 50% initial response): can recommend interval from q8wk to q6wk with 5mg/kg - Special cases: dose 5mg/kg can be considered Injection site reaction Infections: TB and opportunistic infections, autoantibody onset Bone marrow suppression Demyelinating disease (except for ustekinumab) Possible increased risk of malignancies FDA pregnancy category B Renal or Hepatic Impairment There are no dosage adjustments provided in the manufacturer s labeling (has not been studied).

30 Psoriasis/Psoriatic Arthritis Patient case A 54-year-old woman with a 3-year history of psoriasis complains of worsening skin disease and new-onset of joint pain, which makes it a little more difficult for her to walk. Her psoriasis had successfully been managed with topical clobetasol cream. Physical Examination and assessment: Forearms, the trunk with affected body surface area approximately 20% with plaque-type psoriasis Joint evaluation: Inflammation, redness and pain at the fingers of both hands as well as swelling and tenderness at both of her heels. Laboratory studies find rheumatoid factor WNL and ESR 2x ULN. Other findings are WNL. What might be an appropriate treatment to add at this time? A) NSAIDs B) Golimumab C) Methotrexate D) NSAIDs plus oral corticosteroids

31 Psoriasis/Psoriatic Arthritis Key Points Early recognition and treatment 6 Important to prevent irreversible structural damage (esp. patients with psoriatic arthritis) Conventional systemic treatment (DMARDs) 5 Taper once adequate disease control is achieved Biologics: Can be used in combination with other systemic treatments Consider dose reduction or interruption after satisfactory response 3,6 Evaluate risk vs. benefit and appropriateness of patient candidate as long-term efficacy and safety data has only been generated for the approved dosage Therapy interruption Induction dosing should be used for re-induction Can be used with or without MTX for treatment of Psoriatic Arthritis 17 Golimumab (Simponi) & Ustekinumab (Stelara) Note: golimumab is only approved with MTX for the treatment of RA TNF-α Inhibitor (TNFi) Infliximab may have efficacy against severe cases than do other TNFis or anti-ils 7 Effectiveness Psoriatic arthritis: TNFi agents anti-il & Psoriasis vulgaris: anti-il TNFi agents 7 IL-12/23 Inhibitor Ustekinumab (Stelara) shows higher efficacy in BMI 25 7

32 Inflammatory Bowel Disease (IBD) Crohn s Disease vs Ulcerative Colitis General Presentation: 9 Fever, abdominal pain, diarrhea (may have presence of blood, water, or mucus) Rectal bleeding, weight loss. Symptoms vary depends on location Crohn s Disease (CD) Affect the entire GI tract but majority in the ileum May extend to submucosa or deeper Possibly involving fistula Often result in malabsorption Ulcerative Colitis (UC) Limited to rectum and colon Superficial May develop toxic megacolon CD UC

33 Assessment Process for Inflammatory Bowel Disease The specialty pharmacist will review the following with the patients*: 1. Medication profile(both Rx, OTC, supplements) 2. Significant drug-drug interactions Rule out significant DDI: Abatacept (Orencia), anakinra (Kineret), rituximab (Rituxin), Natalizumab (Tysabri) 3. Allergy profile (drug and non-drug) and document reaction Caution for latex allergy: golimumab (Simponi) 4. Medical History (contraindication or concerning to given intended therapy) History of TB: inquire about any history of positive PPD or any type of exposure (even with recent negative PPD) History of fungal infection: Cocci test Hepatitis, multiple sclerosis, Guillain-Barre syndrome, heart failure, pregnancy or planning to become pregnant 5. Physical or functional limitations that would impact self- injection of therapy If limitation is present, ascertain whether there will be a caregiver and train that person when necessary 6. Train for administration technique (Pre-filled Syringe or Pen) 7. Educate patients of side effect profile Medication guide provided to patients as applicable 8. Disease state history & symptom assessment 9. Discuss medication storage and disposal (i.e. provision of Sharps Containers) 10. Refill process: Including follow up assessments and delivery of subsequent medication *See protocol assessment form for more detail

34 Pharmacist Comprehensive Drug Therapy Management Protocols INFLAMMATORY BOWEL DISEASE Medications Managed by Specialty Pharmacy Collaborative Drug Therapy Management through Medication Therapy Protocols TNFi FDA Preg FDA REMS RA Ankylosing Spondylitis Psoriasis, Psoriatic Arthritis Actemra tocilizumab C Y Y Avonex Interferon beta 1a C Y Betaseron Interferon beta 1b C Y Cimzia certolizumab Y B** Y Y Y Y Copaxone glatiramer acetate B Y IBD MS HCV Osteoporosis Cosentyx secukinumab B Y Enbrel etanercept Y B Y Y Y Extavia Interferon beta 1b C Y Forteo teriparatide C Y Y Humira adilimumab Y B Y Y Y Y Orencia abatecpt C Y Pegasys Peg-interferon alfa-2a* X Y Peg-Intron Peg-interferon alfa-2b* X Y Prolia denosumab X Y Y Rebif Interferon beta 1a C Y Simponi golimumab Y B Y Y Y Y Stelara ustekinumab B Y Y *Combo therapy with Ribavirin (Copegus, Rebetol) **

35 Inflammatory Bowel Disease (IBD) Available Treatments Corticosteroid Suppress inflammation during acute flare Not for long term management of IBD DMARDs Non-biologic Induction & maintain remission Aminosalicylates Sulfasalazine, mesalamine Immunomodulators *commonly used with TNFi for IBD Azathiorprine, methotrexate, mercapto purine DMARDs Biologic Infliximab (Remicade) Natalizumab (Tysabri), Vedolizumab (Entyvio) TNFi Adalimumab (Humira), Certilizumab (Cimzia), Golimumab (Simponi) DMARDs: Disease Modifying Anti-Rheumatic Drugs *see protocol appendix for detail. Also see Appendix A, non-biologic immunomodulators commonly used concurrently with TNFi for IBD

36 Inflammatory Bowel Disease (IBD) Stepwise Approach to Treatment Therapy 8 If fail infliximab - Consider testing for antibodies and serum infliximab levels before switching to another biologic. 9,11 - A trial of two TNFis may be warranted before switching to non-tnfi therapy. Induction for mild to moderate CD/UC 5-aminosalicylate or sulfasalazine yes Remission maintenance 5-aminosalicylate or sulfasalazine no Induction for moderate to severe CD (severe UC) corticosteroids If severe or fulminant disease, use IV corticosteroids (CD only) yes Remission maintenance 5-aminosalicylate + steroid taper no If fistulizing, consider induction vs. IV corticosteroids (CD only) Biologic +/- azathioprine or 6- mercaptopurine CD: - Biologic best used in steroidresistant disease - Immunomodulators best used in steroid-dependent disease Surgical evaluation Remission yes no no maintenance azathioprine or 6- mercaptopurine +/- biologic + steroid taper CD: Natalizumab vs. surgery vs. experimental UC: Colecteomy vs. dose adjustment vs. IV cyclosporine Adapted from Mohammad R, Smith MA *see protocol appendix for detail. *NOTE: highlight area(s) indicates Specialty Pharmacy involvement.

37 Inflammatory Bowel Disease (IBD) Step Up vs Traditional Step Down Approach to Treatment STEP DOWN APPROACH Like other auto-immune disease that affects structural damage, new approach is to prevent irreversible damage at early stage 1,10 Use of combined immunosupressants at diagnose to achieve remission Then gradually stepping down therapy 9 TRADITIONAL APPROACH Corticosteroids at initiation Risk: Resistance Dependence Side effects Potential irreversible structural damaged Future therapy model - Early aggressive approach - Early use of immunomodulator - Disease prevention

38 Inflammatory Bowel Disease (IBD) Biologic Treatments Agent (Pharmacology) CD/UC Indication(s) Dosing Comments Adverse Effects and Monitoring Adalimumab (Humira) Fully human, recombinant IgG1 monoclonal antibody Certolizumab pegol (Cimzia) Pegylated, recombinant humanized antibody Fab fragment Golimumab (Simponi) Fully human, recombinant IgG1 monoclonal antibody CD UC CD UC (I) and (M) of remission in patients with moderate to severe disease after conventional therapies fail signs and symptoms of CD and induce remission after infliximab fails (I) and (M) of remission in patients with moderate to severe disease with inadequate response to conventional therapies. of signs and symptoms of disease and (I) and (M) for patients with moderate to severe disease refractory to conventional therapies Patients with moderate to severe disease that failed conventional therapies or requires chronic corticosteroids. (I) and (M) of response and remission, and improvement of endoscopic appearance of mucosa. (I): 160 mg SC on day 1, 80 mg on day 15 (M): 40 mg every other week (I): 400 mg SC at weeks 0, 2, and 4 (M): 400 mg SC every 4 weeks if patient responds to the initial 3 doses. (I): 200 mg SC at week 0, 100 mg SC at week 2 (M): 100 mg SC every 4 weeks Patients older than 40 may have lower clearance. Pharmacokinetics not affected by age or body weight 400-mg doses should be given as two 200 mg injections administered at separate sites. Nasopharyngitis No difference in clearance between older (65 years or more) and younger patients (less than 65 years). ADE: URI, sinusitis, headache, rash, injection site reactions Half-life is about 2 weeks. FDA pregnancy category B Transfer to fetus is maximal in third trimester Potentially immunosuppressing the neonate till six months of age. (I): Induction; (M): Maintenance; URI: upper respiratory tract infection *see protocol appendix for detail. Also see Appendix, Biologic agents SCPS monitoring parameters

39 Inflammatory Bowel Disease Patient case A 30 year old man with history of CD experiences disease worsening and has recent disease exacerbation Examination: moderate size enterocutaneous fistula at the right upper abdominal quadrant Medications: mesalamine (Pentasa) 1g (250mg 4 capsules) 3 times daily and mercaptopurine 100mg/day. The physician would like your recommendations on screening the patient prior to initiating TNFi therapy The following would be appropriate recommendation EXCEPT: A. Rule out tuberculosis B. Admit to the hospital for the administration of all doses C. If patient has history of heart failure NYHA class III-IV, TNFi therapy is contraindicated D. If the patient has treated Hep C infection, you would recommend etanercept

40 Inflammatory Bowel Disease (IBD) Key Points Infliximab (Remicade) 9,11,14 Most studied agent for the treatment of IBD, every attempt should be made to maximize and extend its efficacy before switching to another agent Example: frequency interval or dose Consider antibodies testing as well. See Appendix E for detail Start treatment early in UC Certolizumab (Cimzia) Re-induction may be necessary in patients who relapse while on this medication Step down, more aggressive, earlier treatment with TNFi agents 9 Becoming treatment standard for moderate-severe IBD (more current treatment guideline)

41 Multiple Sclerosis (MS) Diagnosis Diagnosis usually involves clinical and/or radiographic evidence of damage and/or duration of symptoms depending on the type of MS*. MRI scans are used to diagnose and evaluate MS outcomes Certain labs evaluation such as CSF helps rule out other disease Disease Types Progressive Relapsing MS (PRMS): Steady decline since onset with superimposed attacks Secondary Progressive MS (SPMS): Initial relapsing-remitting MS that suddenly begins to have decline without periods of remission Primary Progressive MS (PPMS): Steady increase in disability without attacks Relapsing Remitting MS ( RRMS): Unpredictable attacks, which may or may not leave permanent deficits, followed by periods of remission *Please refer to protocols for details and definitions

42 Assessment Process for Multiple Sclerosis The specialty pharmacist will review the following with the patients*: 1. Medication profile(both Rx, OTC, supplements) 2. Significant drug-drug interactions 3. Allergy profile (drug and non-drug) and document reaction 4. Medical History (contraindication or concerning to given intended therapy) Pregnant or planning to become pregnant (both partners) History of liver disease, mental illness, anemia, thyroid gland disease Others: history of cardiovascular disease, serious infection, seizures 5. Physical or functional limitations that would impact self- injection of therapy If limitation is present, ascertain whether there will be a caregiver and train that person when necessary 6. Train for administration technique (Pre-filled Syringe or Pen) 7. Educate patients of side effect profile Medication guide provided to patients as applicable 8. Disease state history & symptom assessment 9. Discuss medication storage and disposal (i.e. provision of Sharps Containers) 10. Refill process: Including follow up assessments and delivery of subsequent medication *See protocol assessment form for more detail

43 Pharmacist Comprehensive Drug Therapy Management Protocols MULTIPLE SCLEROSIS Medications Managed by Specialty Pharmacy Collaborative Drug Therapy Management through Medication Therapy Protocols TNFi FDA Preg FDA REMS Actemra tocilizumab C Y Y RA Ankylosing Spondylitis Psoriasis, Psoriatic Arthritis Avonex Interferon beta 1a C Y Betaseron Interferon beta 1b C Y Cimzia certolizumab Y B** Y Y Y Y Copaxone glatiramer acetate B Y Cosentyx secukinumab B Y Enbrel etanercept Y B Y Y Y Extavia Interferon beta 1b C Y IBD MS HCV Osteoporosis Forteo teriparatide C Y Y Humira adilimumab Y B Y Y Y Y Orencia abatecpt C Y Pegasys Peg-interferon alfa-2a* X Y Peg-Intron Peg-interferon alfa-2b* X Y Prolia denosumab X Y Y Rebif Interferon beta 1a C Y Simponi golimumab Y B Y Y Y Y Stelara ustekinumab B Y Y *Combo therapy with Ribavirin (Copegus, Rebetol) **

44 Multiple Sclerosis (MS) Available Treatment Corticosteroid Acute treatment with corticosteroids - HIGH dose: Methylprednisolone: IV - 1gram per day x 1 dose OR divided doses for 3-5 days Prednisone: Oral 1250mg per day every other day x 5 doses Disease Modifying Therapy Injection Beta interferons (Avonex, Betaseron, Extavia, Plegridy, Rebif) Glatiramer (Copaxone), Mitoxantrone (Novantrone), Natalizumab (Tysabri) Disease Modifying Therapy Oral Dimethyl fumarate (Tecfidera), Fingolimod (Gilenya), Teriflunomide (Aubagio)

45 Multiple Sclerosis (MS) Medications Managed by Specialty Pharmacy Generic Name (class) Brand name MS Indication Dose & Frequency Common Side Effects Monitor Interferon beta-1a Interferon beta-1b Interferon beta-1a Avonex Betaseron & Extavia Relapsing and single MS Relapsing forms of MS and SPMS with relapses 30mcg IM weekly *First injection must be monitored *Can titrate from 7.5mcg dose up to recommended dose 0.25mg SC every other day Rebif RRMS only 22mcg or 44 mcg SC 3 times weekly Flu-like symptoms: Most people who take AVONEX have flu-like symptoms early during therapy. For many, these symptoms lessen or go away over time and may include: muscle aches fever tiredness chills rash problem sleeping stomach pain Use caution in patients with active liver disease, alcohol abuse, ALT > 2.52 x ULN ALT > 5x ULN OR Leukopenia: Temporarily discontinue therapy or dose until ALT normalizes Thyroid function test if preexisting thyroid disease Consider DISCONTINUATION: If symptomatic liver disease (eg, jaundice) Severe depression or other psychiatric symptoms *same time of the day on same 3 days each week Pregnancy Category C Glatiramer acetate Copaxone RRMS only 20mg SC daily or 40mg SC 3 times weekly *20mg & 40mg dosings are NOT interchangeable *Safest DMD Injection site reactions Flu-like symptoms Headache tiredness nausea and stomach pain urinary tract infection (bladder infection) Pregnancy Category B *see protocol appendix for detail. Also see Appendix A, MS DMDs managed by SHC specialty pharmacy

46 Multiple Sclerosis Treatment Algorithm 15 Relapsing Multiple Sclerosis Teriflunomide are detectable in plasma level for up to 2 years after discontinuation. Wash out period is required if patient becomes pregnant or intends to be pregnant. See Protocol and Appendix B Current therapy 17 : Cholestyramine or Charcoal Escalation approach by Neurologist: Glatiramer acetate OR Interferon (IFN)β-1a OR IFNβ-1b Specialty Pharmacy trial of second 1st line IM/SC Specialty Pharmacy to recommend: Varicella Zoster Vaccine (VZV) at least one month before fingolimid. Accelerated teriflunomide washout if possibly pregnant while on teriflunomide (FDA category X) Medication failure at 3-6 month, or adverse side effects Neurologist trial of 2nd line agents after failed trial of both 1 st line agents: - teriflunomide OR fingolimod OR dimethyl fumarate Neurologist trial of oral medication Induction approach by Neurologist or failed Natalizumab (Tysabri) OR Alemtuzumab (Campath) Medication failure at 3-6 months, or intolerable side effects. *see protocol appendix for detail. Also see Appendix B: Specialty Pharmacy MS medications recommended basic management NOTE: highlight area(s) indicates Specialty Pharmacy involvement.

47 Multiple Sclerosis Patient case The neurologist would like to ask the specialty pharmacist for a recommendation on medication to prevent exacerbations for a newly diagnosed multiple sclerosis female patient who is planning to have a baby with her husband in the upcoming years. What would be the best choice? A. Glatiramer acetate 40mg SC 3 times weekly B. Mitoxantrone 12mg/m 2 IV every 3 month C. Teriflunomide 7mg orally daily D. Interferon beta-1a 30mg IM monthly

48 Multiple Sclerosis Key Points Treatments for MS Current available disease modifying drugs (DMDs) should ONLY be used for patients with relapsing MS Progressive disease without relapse should NOT be treated due to risk of adverse effects without solid evidence of efficacy DMDs should NOT be used in combination due to increase adverse effects without increase efficacy Pregnancy 14 Treatment should be stopped consult neurologist MS is typically 50% less active during pregnancy (presumably due to immunosuppression) Restart treatment early after delivery Teriflunomide (Aubagio) PO pregnancy category X Detectable in plasma up to 2 years after discontinuation See protocol appendix for detail on enhancing medication elimination if patient becomes pregnant or plans to be pregnant Interferon therapy 17 Require close monitor *see protocol and appendix for more detail Consider therapy discontinuation if experience severe adverse effects such as symptomatic liver disease, and/or psychotic episodes.

49 Pharmacist Comprehensive Drug Therapy Management Protocols ANKYLOSING SPONDYLITIS Medications Managed by Specialty Pharmacy Collaborative Drug Therapy Management through Medication Therapy Protocols TNFi FDA Preg FDA REMS RA Ankylosing Spondylitis Psoriasis, Psoriatic Arthritis Actemra tocilizumab C Y Y Avonex Interferon beta 1a C Y Betaseron Interferon beta 1b C Y Cimzia certolizumab Y B** Y Y Y Y Copaxone glatiramer acetate B Y IBD MS HCV Osteoporosis Cosentyx secukinumab B Y Enbrel etanercept Y B Y Y Y Extavia Interferon beta 1b C Y Forteo teriparatide C Y Y Humira adilimumab Y B Y Y Y Y Orencia abatecpt C Y Pegasys Peg-interferon alfa-2a* X Y Peg-Intron Peg-interferon alfa-2b* X Y Prolia denosumab X Y Y Rebif Interferon beta 1a C Y Simponi golimumab Y B Y Y Y Y Stelara ustekinumab B Y Y *Combo therapy with Ribavirin (Copegus, Rebetol) **

50 Assessment Process for Ankylosing spondylitis The specialty pharmacist will review the following with the patients*: 1. Medication profile(both Rx, OTC, supplements) 2. Significant drug-drug interactions Rule out significant DDI: Abatacept (Orencia), anakinra (Kineret), rituximab (Rituxin), Natalizumab (Tysabri) 3. Allergy profile (drug and non-drug) and document reaction Caution for latex allergy: golimumab (Simponi) 4. Medical History (contraindication or concerning to given intended therapy) History of TB: inquire about any history of positive PPD or any type of exposure (even with recent negative PPD) History of fungal infection: Cocci test Hepatitis, multiple sclerosis, Guillain-Barre syndrome, heart failure, pregnancy or planning to become pregnant 5. Physical or functional limitations that would impact self- injection of therapy If limitation is present, ascertain whether there will be a caregiver and train that person when necessary 6. Train for administration technique (Pre-filled Syringe or Pen) 7. Educate patients of side effect profile Medication guide provided to patients as applicable 8. Disease state history & symptom assessment 9. Discuss medication storage and disposal (i.e. provision of Sharps Containers) 10. Refill process: Including follow up assessments and delivery of subsequent medication *See protocol assessment form for more detail

51 Ankylosing Spondylitis (AS) Treatment Algorithm 16 Active AS NSAIDs: -Use continuously, not on demand -No preferred NSAID in general -Adequate trial: intolerance or no response to > 2 different NSAIDs over 1 month, or incomplete response over 2 months. AS remains active TNFi contraindicated TNFi indicated - Sulfasalazine (SSZ) or pamidronate - Avoid non-tnfi biologics No IBD and no iritis: - No single preferred TNFi - Recommended: adalimumab or certolizumab or etanercept or golimumab or infliximab (IV) Systemic Glucocorticoids: -NOT recommended -Possible exceptions: consider if peripheral flare, pregnancy, or IBD flare, with rapid tapering. + IBD or + iritis: - preferred TNFi: adalimumab or infliximab (IV) - avoid etanercept - at home topical glucocorticoids for recurrent iritis - ophthalmologist for acute iritis Stable AS SHC Specialty pharmacy Isolated sacroiliitis or peripheral arthritis or enthesitis -Try an alternative TNFi Local glucocorticoids by MD AS remains active SHC Specialty pharmacy NSAIDs: -Use on demand; No preferred NSAID Adapted from ACR/SAA: AS Treatment Guideline 16 -TNFi alone (monotherapy) -Avoid TNFi & NSAIDs; avoid TNFi & SAARDs; possible exception is for the use of low dose MTX with TNFi to decrease potential development of antidrug antibodies *see protocol appendix for detail. Also see Appendix C: Recommended AS Medication Management. *NOTE: highlight area(s) indicates Specialty Pharmacy involvement.

52 Ankylosing Spondylitis Biologic Treatment CLASS MEDICATION DOSE FREQUENCY Comments Common Side Effect TNF-α Inhibitor - AVOID in pts with NYHA class III-IV heart failure - Vaccination and TB screening MUST be done prior to therapy initiation - Monitor for infection Adalimumab (Humira) Certolizumab (Cimzia) Etanercept (Enbrel) 40mg SC 400mg SC THEN 200mg SC 50mg SC, 25mg SC Every 14 days, may to 40mg weekly in pts not taking MTX 400mg SC week 0, 2 and 4 THEN 200mg SC every 2 weeks Weekly or twice weekly Less antigentic than other TNFis *Best response when in combination with MTX *Recommended in patients with Hepatitis C (Child-Pugh class A) Headache, sinus infections, rash, nausea Upper respiratory infections (flu, cold), rash, urinary tract infections (bladder infections) Headache, sinus infections. Golimumab (Simponi) 50mg SC Monthly with or without MTX CI: Latex allergy Sinus infections, rash *See protocol appendix for more detail

53 Ankylosing Spondylitis Patient case A 35-year-old man was previously empirically treated with indomethacin for arthritis with some improvement. Today he presented with acute pain and swelling of one knee and had developed an iritis in his left eye, low back pain and stiffness. He has pan in both sacroiliac joints. On examination, the joint was tender and restricted in movement. X-ray Periarticular osteoporosis of the knee Changes of ankylosing spondylitis shows bony ankyloses between lambar vertabrae Lab: Erythrocyte sedimentation rate (ESR) 102mm/h Hb 10.6g/dL Rheumatoid factor (-) Polymorphonuclear leucocytosis from knee effusion aspiration: no organisms (-), rheumatoid factor (-) HLA-B27 (+) from tissue typing Which medication would you recommend to initiate for this patient? A. Etanercept 50mg SC weekly B. Golimumab 50mg SC weekly C. Adalimumab 40mg SC every 14 days D. Certolizumab 400mg SC monthly

54 Pharmacist Comprehensive Drug Therapy Management Protocols Summary of Safety Profiles for Medication Managed by Specialty Pharmacy Do NOT use biologics in combination due to risk of serious infection TNF-α Inhibitor (TNFi) AVOID in patients with NYHA class III-IV heart failure Do NOT use in Multiple Sclerosis patients due to worsening of demyelination Vaccination and TB screening MUST be done prior to therapy initiation NO live vaccine during treatment Monitor for infection Can switch to another TNFi biologic if significant disease activities still present after 3 months 6 months if patient is taking non-tnfi biologic Infliximab (Remicade) Prefer in patients treated for (solid or non-melanoma) malignancy within 5 years Etanercept (Enbrel) Prefer in patients with treated Hepatitis C (Child-Pugh class A) *See protocol appendix for more detail

55 Pharmacist Comprehensive Drug Therapy Management Protocols Summary of Safety Profiles for Biologics Continued Switching therapy 7 Due to treatment failure? Advise switching without washout period at time of next dose (standard induction follow by maintenance dose) Due to adverse effects? Consider a treatment-free interval (washout) until safety parameters are stable Newer treatment approach to therapy 14 Starting treatment as EARLY as possible Stratify therapy based on severity of disease and risk of adverse effects New approach to therapy: Step Down Approach Start with more aggressive therapy (eg.,biologics, combined therapy) Prevent irreversible structural damage Avoid corticosteroids dependence and adverse effects where appropriate Medications to AVOID in pregnancy 17 Denosumab (Prolia) Leflunomide (Arava) Methotrexate (Trexall, Rheumatrex) Ribavirin (Copegus, Rebetol) - alone or in combination with other drugs BOTH partners must use 2 forms of contraception Teriflunamide (Aubagio) (detectable in plasma for up to 2 years after medication discontinuation) *See protocol appendix for more detail

56 Sharp Specialty Pharmacy Monitoring Guidelines Biologic agents used for various indications: Monitoring Guidelines See protocol appendix for more detail at SharpNet Policy & Procedure Website

57 Pharmacist Comprehensive Drug Therapy Management Protocols Which medication has MAX life time duration is 2 years? Which medication is still detectable in the plasma level even 2 years after discontinuati on? Which biologic agent is recommended for patient with MS? Which agent is recommended to be used for treatment of progressive MS? Which Medication must be AVOID for couples who plan to have a child? Which medications must be used with MTX for the treatment of RA? What medication is the most studied agent for the treatment for IBD? Which biologic is preferred for patient with history of treated Hepatitis C? What is the dosing range and frequency for MTX for the treatment of RA?

58 References Patient Cases answer keys: D (RA), D (Osteoporosis), C (Psoriasis), B (IBD), A (Multiple Sclerosis), C (Ankylosing Spondylitis) 1. Tanaka Y. Next stage of RA treatment: is TNF inhibitor-free remission a possible treatment goal? Ann Rheum Dis. 2013:72(suppl 2):ii124-ii127. doi: /annrheumdis A - Singh JA et al: 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care & Research; Special article: Assessed November 25, B - Singh JA, Furst DE, Bharat A, et al update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012:64(5): doi: /acr Burke RA, White ND. Biologic Disease-Modifying Antirheumatic Drugs. In: Murphy JE, Lee MW, eds. Pharmacotherapy Self-Assessment Program, 2014 Book 2. Chronic Illnesses. Lenexa, KS: American College of Clinical Pharmacy, 2014: National Osteoporosis Foundation. Clinician s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; ( 5. Menter a et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol 2008;58: IBD 6. Mrowietz U et al. A consensus report on appropriate treatment optimization and transitioning in the management of moderate-to-severe plaque psoriasis. Journal of the European Academy of Dermatology and Venereology. 2014, 28, Umezawa et al. Algorithm for Selecting Ideal Biologic Treatment for Psoriasis. J Clin Exp Dermatol Res 2015, 6:5 8. Afif W et al. Clinical Utility of Measuring Infliximab and Human Anti-Chimeric Antibody Concentrations in Patients With Inflammatory Bowel Disease. The American Journal of Gastroenterolog. May 2010;105: Mohammad R, Smith MA. Biologic Therapies for Gastrointestinal Diseases. In: Murphy JE, Lee MW, eds. Pharmacotherapy Self-Assessment Program, 2014 Book 2. Chronic Illnesses. Lenexa, KS: American College of Clinical Pharmacy, 2014: D Haens et al. Early Combined Immunosupression or Conventional Management in Patients with Newly Diagnosed Crohn s Disease; an open randomised trial. Lancet 2008; 371: Restarting or switching from infliximab: ( ARUP Lab Infliximab Activity and Neutralizing Antibody ( 12. Talley N et al. An Evidence-Based Systematic Review on Medical Therapies for Infl ammatory Bowel Disease. Am J Gastroenterol 2011; 106:S2 S Scolding N, Barnes D, Cader S, et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol 2015;15: Kinikar SA. Multiple Sclerosis. In: Murphy JE, Lee MW, eds. Pharmacotherapy Self-Assessment Program, 2015 Book 2. CNS/Pharmacy Practice. Lenexa, KS: American College of Clinical Pharmacy, 2015: Treatment Algorithm. University Hospital System Algorithm for Treatment of Relapsing Multiple Sclerosis. Assessed November, 10, Ward MM, Deodhar A, Akl EA et al: ACR/SAA/SPARTAN TREATMENT RECOMMENDATIONS IN AS. Arthritis Rheumatol Sep 24. doi: /art [Epub ahead of print] 17. Lexicomp Online, Hudson, Ohio: Lexi-Comp, Inc.; November, Patient Cases answer keys: D, D, C, B, A C