Rituximab PROTOCOL FOR PAEDIATRIC RHEUMATOLOGY

Transcription

1 Rituximab PROTOCOL FOR PAEDIATRIC RHEUMATOLOGY 1. Backgrund and indicatins Rituximab is a mnclnal antibdy that wrks by remving B-cells (a type f white bld cell that prduce antibdies). The aim f the B cell depletin is t reduce aut-antibdies (such as rheumatid factr) and thereby disease activity. These B-cells reappear after 4-12 mnths after therapy. CD27 + B-cells representing memry B-cells can remain suppressed fr 2 years after depletin. The use f Rituximab is cnsidered in patients with active Juvenile nset Systemic Lupus Erythematsus (JSLE), dermatmysitis, vasculitis, RF psitive Plyarticular JIA and widespread sclerderma wh have nt respnded t standard treatments, such as Azathiprine, Mycphenlate Mfetil, Methtrexate, sterids and apprpriate bilgics. Rituximab can be used in cmbinatin with Prednislne, Hydrxychlrquine, Methtrexate r Cyclphsphamide. Other immunsuppressants are usually temprarily stpped during rituximab treatment, but may be recmmenced afterwards. Rituximab is nt currently licensed fr use in children, but has been extensively used in adult rheumatic diseases with a gd safety prfile. 2. Dse and frequency Prir t prescribing, ensure that: Ratinale and funding fr Rituximab treatment established & Pharmacy infrmed paedncpharmacists@uh.nhs.uk Patient and parents have received and understand infrmatin n Rituximab Recent weight recrded n EPR Rituximab 750mg / m 2 (runded up t the nearest 100mg, max dse 1 gram) 2 dses given days apart. This can be repeated after 6 mnths if needed. 3. Prcedures 3.1. Pre-treatment tests Prir t the first infusin, all patients shuld have had the fllwing (unless reasn fr deviatin recrded by Cnsultant in the medical ntes): Screen fr hepatitis A, B and C CXR shuld be dne within last year The paediatric rheumatlgy team may advise patients stp anti-hypertensives 12 hurs prir t administratin (t reduce risk f hyptensin) 3.2. Cannulatin and blds n the day Baseline FBC, ESR, U&E s, LFT s, CRP, Lymphcyte subsets CD19 r CD20 & Immunglbulins (G, A & M). Rheumatid factr titre if requested by paediatric rheumatlgy team

2 These shuld all be repeated n day 7-10 after the 1 st dse f Rituximab. Repeat Lymphcyte subsets (CD19 r CD20) & Immunglbulins (G, A & M) after 2 mnths, then 3 mnthly until B cells are nrmal. If patient desn t have an appintment t have these dne, please infrm paediatric rheumatlgy CNS Clerking Rituximab SHOULD NOT BE GIVEN if: Patient has had a severe allergic reactin t Rituximab r any ther prduct that was made with murine prteins. There is evidence f current, active infectin The patient has had TB (tuberculsis), unless suitable antibitics are being given t treat TB, r if there has been recent cntact with smene wh might have TB. A CXR must have been perfrmed in all patients (+/- mantux/elispt if cnsidered high risk). Patient is pregnant. Sexually active patients must use effective birth cntrl while taking rituximab and fr 12 mnths after treatment has ended. In the fllwing circumstances please discuss with the paediatric rheumatlgy team as it may be necessary t withhld the Rituximab. Recent infectin r cntact with an infectius disease. The infectin culd be an pen cut r sre, a chest infectin r an infectin that affects the whle bdy (such as the flu r chicken px). The patient has heart failure r ther heart cnditins, multiple sclersis, r Guillain-Barré syndrme, r if the patient has experienced numbness, tingling, r had a seizure. Lived in r visited an area f the cuntry where an infectin called histplasmsis r cccidiidmycsis (an infectin caused by a fungus that affects the lungs) is cmmn. Abnrmal bld results Lw bld cell cunt (Hb less than 100, platelets less than 150), symptms and signs f which may include bruising, bleeding, pallr, r if patient has a temperature abve 37.5 c. Neutrphils less than 1.5 Liver Functin - If ALT mre than 120 Vaccinatins Live vaccines such as ral pli, rubella, MMR, chicken px, BCG and yellw fever shuld nt be given whilst patient is n Rituximab. Shuld nn-live vaccinatins be required, these shuld be cmpleted at least 4 weeks prir t cmmencing the next curse f Rituximab. Annual flu vaccines are recmmended and shuld be given.

3 It is nt knwn whether patients may need re-immunisatin f previus nn-live vaccines fllwing rituximab. Once immunglbulins back t nrmal, check specific antibdies (Tetanus, Hib, Pli etc) frm previus immunisatins and if lw, re-immunise and recheck levels. If patient has a cntaminated wund (has received rituximab within the last 6 mnths) and there is any dubt abut the patient s tetanus status, then a tetanus immunglbulin shuld be administered Pre-medicatin IV Methylprednislne:100mg (Dilute in mls 0.9% sdium chlride) IV Chlrphenamine: 1 5 years = 2.5 mg 6 12 Years = 5 mg Over 12 years = 10mg PO Paracetaml: 15mg/kg (max 1g) 3.5. Drug preparatin & strage Stre vials in a refrigeratr (2 C 8 C). D nt freeze. Keep the vial(s) in the uter cartn in rder t prtect frm light. Each Rituximab vial cntains 10mg/ml slutin in the fllwing sizes: 100mg/10ml 500mg/50ml ANTT shuld be used thrughut. Calculate dse f Rituximab and fluid vlume t be withdrawn Dilute the required dse f Rituximab with 0.9% Sdium Chlride t make a final cncentratin f 2mg/ml. Gently invert t mix, t avid faming. Prir t administratin slutin shuld be inspected fr particulate matter r discluratin. If this is present discard the slutin and infrm pharmacy. After preparatin slutin must be administered immediately, r within 4 hurs if stred in fridge Administratin rate and mnitring A PHYSICIAN MUST BE CLOSE BY FOR ALL INFUSIONS Mnitr fr cytkine release syndrme with fevers and rigrs. Premedicatin and slw infusin rates might help t avid this. Give Pre Medicatins First give the IV Chlrphenamine and PO Paracetaml Give IV Methylprednislne ver 30mins. Put up flush ver 30mins (This shuld ensure a 30min gap between the Methylprednislne and the Rituximab.

4 Observatins Baseline TPR and BP prir t infusin TRP and BP every 15mins fr 1 hur Cntinue TPR and BP every 30 minutes thrughut infusin and until 1 hur pst infusin Infusing Rituximab Fr the initial infusin (Day 0) start at 25mg/hur, which can be increased by increments f 25mg/hur every 30mins t a maximum f 200mg/hur as tlerated. Fr the 2 nd (Day 14) infusin start at 100 mg/hur, if tlerated the rate can be increased by 100 mg/hur every 30 minutes, t a maximum rate f 400 mg/hur. Time (minutes) Infusin rate (mg/hur) Infusin rate (ml/hur) Set vlume t be infused (ml) T cmplete infusin Ttal time t cmplete this infusin is apprximately 5 hurs Upn cmpletin flush with 20ml 0.9% sdium chlride at same infusin rate. Keep cannula insitu fr this hur, then it can be remved. In the event f an infusin related reactin the infusin rate shuld be reduced t half the current rate and cntinue t mnitr clsely. In the event f a mderate t severe reactin the infusin shuld be interrupted immediately, symptmatic treatment administered and the infusin rate restarted at half the previus rate when symptms have reslved. Please discuss with rheumatlgy team if cncerned. Incidence f infusin-related adverse effects decreases with subsequent infusins. 4. Side effects and infusin reactins Mst patients d nt experience side effects and pre medicatin is given t reduce this. Pssible side effects include: 1) Infusin Reactins: Can ccur in 10% f patients treated with rituximab, including hyptensin, brnchspasm. These are usually reversible by stpping the infusin, administering anti-pyretics & antihistamines. The infusin can nrmally be recmmenced at a slwer rate. Occasinally xygen, IV brnchdilatrs & gluccrticids are required. The patient shuld be encuraged t reprt any adverse feelings.

5 2) Skin rashes: Itchy skin rashes have ccurred in a few peple usually arund hurs after the secnd r third infusin and can last fr several days. Anti-histamine can be prescribed t reduce this. N-ne has stpped the drug due t itching, the rashes usually g away after a few mre dses. 3) Increased risk f infectin: As with all arthritis treatment there is an increased risk f infectin. Bld test shuld be mnitred regularly t check fr immune suppressin. 4) Other side effects can include cnjunctivitis, abdminal pain and mre nn-specific symptms such as headaches r temprary changes t bld results including WCC and ALT. If these symptms r any ther unusual symptms ccur please cntact the n-call paediatric rheumatlgy cnsultant via switchbard Allergic Reactin If the fllwing shuld ccur STOP THE INFUSION AND INFORM A DOCTOR n the ward and the paediatric rheumatlgy team (see cntact details at end f prtcl): Swelling f the lips Hives (red, raised, itchy patches f skin) Difficulty breathing Chest pain The presence f high r lw bld pressure (change by mre than 20mmHg). Symptms f lightheadedness, dizziness r headache may alert t the presence f a marked change in bld pressure. Cntacts fr Paediatric Rheumatlgy Team 1. Paediatric Rheumatlgy Nurse Specialists (7)37341 cnspaedrheum@uh.nhs.uk 2. Paediatric Rheumatlgy cnsultant n-call via switchbard 3. Out f hurs cntact can be made with the n-call Paediatric Rheumatlgy cnsultant via switchbard References SPC fr Rituximab fund at BSPAR Guidelines n Rituximab use in Paediatric Rheumatlgy. Marks,S, et al (2005) B Lymphcyte depletin therapy in children with refractry systemic erthematsus. Arthritis & Rheumatism.V52(10) p Nwbi, O et al (2008) Rituximab therapy fr juvenile-nset systemic lupus erythematsus. Pediatric Nephrlgy. 23, P A retrspective seven-year analysis f the use f B cell depletin therapy in systemic lupus erythematsus at University Cllege Lndn Hspital: the first fifty patients. Lu TY, Ng KP, Cambridge G, Leandr MJ, Edwards JC, Ehrenstein M, Isenberg DA. Arthritis Rheum Apr 15;61(4): Kendall,E, Inness, E, Parsns, E, Wilkinsn, N (2012) Audit f Bld Mnitring fr Patients receiving Bilgic Therapies. Oxfrd Paediatric and Adlescent Rheumatlgy Centre. Nuffield Orthpaedic Centre. BSR BHPR guidelines n the use f Rituximab in RA, Dec 2011 Mdified frm GOSH Infusin Guideline fr Rituximab (2013)