Week 7: Gout, Osteoarthritis, Rheumatoid Arthritis, SLE Flashcards
Gout
most common form of inflammatory arthritis
“disease of kings
Gout epidemiology
increased age=increased risk
3-4:1 male: female
(female risk increases w. age w. estrogen loss
linked to:
comorbid conditions
diet
medication use
renal erate transporter gentotype (SLC2A9, ABCG2, SLC17A3, SLC22A12)
Patho of gout
purines (diet, tissue breakdown)-> uric acid (metabolized by uricase in most mammals, not humans)->metabolized to allantoin and excreted from body
UA soluble at conc <6.7 mg/dL
saturation causes crystallization into joints
phagocytosed triggering an immune respone
excess serum uric acis caused by
*overperoduction of urate
or underexcretion of urate
gout and disease states
DM
HLD
obseity
renal insufficiency/CKD
HTN
organ transplantation
CHF
FOOD AND GOUT
hyperuricemic
*meat
seafood
beer and liquor
soft drinks
fructose
Uricosuric (increase uric acid excretion in urine)
*coffee
dair
vitamin C
meds and gout
hyperuricemic meds
*THIAZIDES
LOOP DIURETICS
NICOTONIC ACID
ASPIRIN (<1G/DAY)
others..
cyclosporine
tacrolimus
pyrazinamide
levadopa
ethambutol
uricosuric meds
LOSARTAN
FENOFIBRATE
classic GOUT PRESENTATION
overall characteristic of flares:
common areas affected:
can be precipitated by:
presentation waxes and wanes . periods of asymptomatic until pt experiences acute gout attack
gout flare: (attack): onset within 24 of severe pain, erythema and swelling in a single or multiple joints
Podagro: first metacarsopholangeal joint (big toe) joint involvement most common
may calso effect ankles, fingers, wrists and elbows
can be precipitated by
alcohol ingestion
high purine ingestine
stress
meds (including UA lowering agents
other clinical presentations of gout
classic gout: monarticular arthritis, frquently attacks first metatarsalpholangeal join, although other joints of lower extremeitie are also frquently involved. affected joint i swollen, erythamatous, and tender
interval gout: asymptomatic period inbetween attacks
tophaceous gout: deposit of urate crystalls in soft tissues, . complications include soft tissue damage, deformity, joiint destruction, and nerve compression syndromes such as carpal tunnel syndrome
atypical gout: polyarthritis affecting any join upper or lower extremity. may be confused with rheumatoid or osteoarthritis
gout nephropathy: nephrolithiasis . acut and CKD
what is a tophi
mass of urate deposits in bone, cartilage, joints or tissues
gout dx
dx by synovial fluid aspiration and identification of monosodium urate crystals
* not routinely performed
!!Flare/ attack presentation along w. serum acid>6.8 mg/dL indicated treatment for gout!!
**note. elevated serum uric acid levels alone w. no presentation of gout symptoms does not warrant gout treatment
Goals of therapy for acute gout
reduce pain and duration of attacks
geenral anti-inflammatory agents for acute gout treatment
NSAIDS
colchcine
corticosteroids (oral or intrarticular)
General Acute Gout pharmacotherapy
NSAIDS
moa:
examples:
dosage:
General Acute Gout pharmacotherapy
moa:cox INHIBITION
examples: Indomethacin, naproxen, and sulindac have fda approved indications for gout (but any nsaid will do for the most part)
dosage: –
nsaid considerations for use in acute gout
timing:
when to avoid use:
timing of admin (<24 hrs) more important to treatment success than choice of agent
resolution of symptoms usually within 5-8 days
(may require treatment beyond 7 days)
AVOIDE USE IN:
*renal insufficiency/ failure
*bleeding disorder/anticoagulated pts
*peptic ulcer disease
*CHF
*older adult (>75)
General Acute Gout pharmacotherapy
Colchicine
moa:
examples:
dosage:
General Acute Gout pharmacotherapy
moa: inhibitoin og b-tubulin polymerization into microtubules, causing downregulation of inflammatory patways (also prevents activayion, degranulation and migration of neutrophils
examples:–
dosage:
1.2 mg (2 tabs) po x 1 then 0.6 mg 1 hr later
*may have to continue beyond this dosage w. colchicine or additional therapy
Considerations/pearls for colchicine
often causes GI symptoms
can cause:
*hematologic abnormalities
*rhabdomylisys
a) renal dysfunction and elderly patients are at increased risk
b)concaminant use of 3a4 inhibitors, pgp inhibitors, fibrates, and statin may increase risk of myopathy
Dose adjustment for..
*Crcl< 30mL/min
*severe hepatic impairment (no recommendations. if being used, reduce dose)
DDI: concaminant cyp3a4 and pgp inhibitor users
*dose adjustments necessary (for prophylactic users too)
do not dose colchicine for flare therapy if using prophylaxis
*concurrent use of colchicine and pgp or strong cyp3a4 inhibitors is CI in renal or hepatic impairment (fatal toxicities reported)
Colchicine DDI
DDI mechanism: Strong CYP3A4 inhibitors
examples:
dose adjustments:
*acute gout flare:
*ppx gout flare:
Colchicine DDI
DDI mechanism: Strong CYP3A4 inhibitors
examples: CLARITHROMYCIN, ITROCONAZOLE, KETOCONAZOLE, DARUNAVIR/RITONAVIR, atazanavir, nefazodone, lopinavir/ritonavir
dose adjustments:
*acute gout flare: single 0.6 mg dose followed by 0.3 mg 1 hr later dose to be repeated no earlier than 3 days
*ppx gout flare: 0.3 mg once qod to 0.3 mg once daily
Colchicine DDI
DDI mechanism: Moderate CYP3A4 inhibitors
examples:
dose adjustments:
*acute gout flare:
*ppx gout flare:
Colchicine DDI
DDI mechanism: Moderate CYP3A4 inhibitors
examples: VERAPAMIL, DILTIAZEM, ERYTHROMYCIN, FLUCONAZOLE, aprepitant, amprenavir
dose adjustments:
*acute gout flare: 1.2 mg dose; dose to be repeated no earlier than 3 days
*ppx gout flare: 0.3-0.6 mg daily (0.6 mg dose may be given as 0.3 mg twice daily)
Colchicine DDI
DDI mechanism: PGP inhibitors
examples:
dose adjustments:
*acute gout flare:
*ppx gout flare:
Colchicine DDI
DDI mechanism: PGP inhibitors
examples: CYCLOSPORINE, AMIODARONE, RANAZOLINE
dose adjustments:
*acute gout flare: single 0.6 mg dose; dose to be repeated no earlier than 3 days
*ppx gout flare: 0.3 mg once qod to 0.3 mg once daily
General Acute Gout pharmacotherapy
Coticosteroids
moa:
examples:
dosage:
General Acute Gout pharmacotherapy
Coticosteroids
moa: reduces polymorphnuclear leukocyte migration, supress the lymph system
*immune supression and anti-inflammatory effects
examples:prednisolone, prednisone, methylprednisolone, intra-articular triamcinolone
dosage:
*prednisolone 30-35 mg po x5days
*prednisone 30-60 mg po qd for 2 days with taper over 10 days
*intrarticualar triamcinolone:
a) large joint (knee):40 mg as a single dose
b)medium joint (eg wrist, ankle, elbow): 30 mg as a single dose
c) small joint (eg toe, finger): 10 mg as a single dose
corticosteroids considerations for acute gout flare
*if only one or two joints are involved, either IA or oral are recommended
if ana attack i polyarticular, systemic therapy is indicated
consider alternaive if dm, chf OR SEVERE gerd OR pud
Safe for use in renal impairment
AE (with short term use): leukocytosis, increases appetite, modd changes, elevated BG
Chronic therapy of gout goal
prevent future attacks and hyperuricemic sequelae by maintainging SUA <6.0
*prevent arthropathy, tophus frmation, nephrolithiasis, joint damage
General Chronic Gout pharmacotherapy classes and examples
Xanthine Oxidase Inhibitors
*Allopurnol
*Febuxistat
Uricosurics
*probenacid
Pegloticase
General Chronic Gout pharmacotherapy
Allopurinol
moa:
dosage:
AE:
DDI:
Considerations:
General Chronic Gout pharmacotherapy
moa: Xanthine oxidase inhibitor. blocks conversion of hypoxanthine to xanthine to uric acide
dosage:
starting: 50-100 mg qday
*100 mg po qd starting for normal renal function
*50 mg po qd in CKD stage 4 or worse
*increase q2-5 weeks to target <6 mg/dL
*may have to increase up to 800 mg to achieve target SUA
*can go above 300 mg po qday even in renal impairment depsite renal dosage adjustment PI recommendations
ae:
*rash:~2%. increased with coad w. amoxacillin, ampicillin, thiazides, ace-i. Prob best to d/c drug. mild rash can progress to SJS
*DRESS
*occurs in 0.1 pts
IMMEDIATELY d/c
DDI:
*warfarin (increases risk of bleeding)
*6-MP, azathioprine, theophylline (allopurinol can icnrease levels of these
*amaxaillin, ampicillin, thiazides, ace-i increase risk of rash
considerations:
*1st line therapy
*can be used overproducers or underexcreters of uric acid
General Chronic Gout pharmacotherapy
Febuxistat (Urolic)
moa:
dosage:
AE:
CI:
DDI:
Considerations:
General Chronic Gout pharmacotherapy
moa: chemically engineered selective xanthine oxidase inhibitor
dosage:
starting: 40 mg once daily;
may increase to 80 mg qd in pts who do not achieve serum uric acid level <6 mg/dL after 2 weeks
AE: headahce, arthtalgias, abd. pain, NV, abnormal lft, FLUSHING AND DIZZINESS
CI: 6-MP, azathiopurine, theophylline
DDI: 6-MP, azathiopurine, theophylline (febuxistat inc levels of these)
Considerations:
BBW: inc. cv death in pts with cv disease
*theoretically can be used in ppl with allopurinol hypersensitivity, not sturcturally related.
*no dose adjustments required for mild-mod renal or hepatic impairment. use caution in severe hepatic impairment or crcl<30
*concam nsaid or colchicine ppx may take up to 6 mo. to help prevent gout flares per package insert
*if gout flare occurs, febuxistat doesnt need ot be d/c
General Chronic Gout pharmacotherapy
Probenacid
moa:
dosage:
AE:–
CI:
DDI:
Considerations:–
General Chronic Gout pharmacotherapy
Probenacid
moa: inhibits reabsoprtion of uric acid at proximal conviluted tubule, increasing excretion
dosage:
250 mg bid for 1 wek, may incr to 500 mg bid if needed, may increase to a mac od 2g/day (increase in 500 mf increments q4w)
AE:–
CI:
*Crcl<50 mL/min,
*hx of nephrolithiasis
* use of pcn, methotrexate, carbapenems (doripenem, meropenem) (inc conc due to decreased renal secretion
*salicylates, decreased efficacy of probenecid
DDI:use of pcn, methotrexate, carbapenems (doripenem, meropenem) (inc conc due to decreased renal secretion
*salicylates, decreased efficacy of probenecid
Considerations:–
General Chronic Gout pharmacotherapy
Pegloticase
moa:
dosage:
AE:
CI:–
DDI:–
Considerations:
General Chronic Gout pharmacotherapy
Pegloticase
moa: pegilated recombinant uricae: converts uric acid to allantolin so it can be excreeted
dosage:
*IV: 8mg q2w over atleast 2 hrs
AE:infusion rections, anaphylaxis
CI:–
DDI:–
Considerations:
BBW: can cause anaphylaxis and infusion reactions
*occurs within 2 hrs
*premed w. antihistamines or corticosteroids
*ppx w. low dose colchicine or nsaid x 6 mo
Mgt of acute gout attack
General principles
acute gouty arthritis attaks should be treates w. pharm therapy
pharm treatment should be initiated ithin 24hrs of acute gout attack onset
ongoing pharm urate lowering therapy (ULT) should not be interrupted during an acute gout attack
guidelines for acute gout attack
- assess severity
A) if pt has mild(0-4)-mod(5-6) pain, and an attack effecting 1 or few small joints, or 1-2 Large joints->can consider monotherapy
B) if pt has severe (7+) pain, and polyarticular attack or an attack affecting multiple large joints-> can consider initial combo therapy (will discuss in another card)
2) Selecting Monotherapy
a)NSAID
b)Systemic corticosteroid
c) colchicine
***supplementation w. topical Ice for any gout attack
3) Assess treatment outcome
A) if inadequate response->
*consider switching to alternate monotherapy
*consider combo therapy
B) if successful outcome
*pt education: including diet and lifestyle, role of uric acid excess in gout and as key treatment target; prompt self trt of subsequent acute gout attacks
*consider indications for ULT or adjustment of ongoing ult
Guideline acute flare dosing for colchicine therapy
If pt has not been on ppx colchicine or not treated w. colchicine for an acute attack in the last 14 days..
can use oral colchicine:
*1.2 mg, then 0.6 mg 1 hr later
* then gout attack ppx can be started(0.6 mg po qd or bid), beginning 12 hrs or later, and continued until the acute gout resolves
if pt is on ppx colchicine or has recieved colchicine for an acute attack w.in the past 14 days..
*choose alternative therapy (NSAID or coricosteroid)
guideline flare dosing for nsaid or selective cox2
full fda or ema approved dose of nsaid or a cox2 inhibitor…
*continue intitial trt at full dose until gout attack has completely resolved
guideline fare dosing
corticosteroids
1) assess extent of joint involvement
A) if 1-2 large joints: can consider IA CCS
B) all cases of gout:
ORAL:
a)prednisone 0.5 mg/kg/day
*duration: 5-10 dys then stop OR 2-5 days at full dose then taper for 7-10 days then stop
b) methylprednisolone dose pack (6 day course)
IA:
dose dpeends on joint size (w. or w.o oral trt)
IM:
traiamcinolone acetonide 60 mg, then oral prednison as above (WONT BE TESTED ON THIS)
combo therapy for acute gout attack
when to consider:
recommendations:
consider if
*severe attack (polyarticular)
*pts not responding to initial monotherapy
recommended combos
*nsaid +colchicine
*PO CCS+ colchicine
*IA CCS+ NSAID+/- colchicine
*IA CCS+ PO CCS_/- colchicine
NOTE: DO NOT USE PO NSAID AND PO CCS AS COMBO THERAPY
Gout chronic therapy gprinciples
not all pts require chronic therapy
lifestyle modification recommended for all pts, regardless of disease activity
chronic therapy=UA lowering therapy +Flare prophylaxis
*UA lowering therapy can illicit flares because remodeling of crystal deposits can dislodge? and trvael illiciting a flare elsewhere
*ppx flare therapy should be given concaminanly w. Uric acid lowering therapy (ULT)
chornic therapy shuold not be stopped during flare
Nonpharm recommendations for gout treatment
Stay hydrated
Exercise
Encourage smoking cessation
Healthy overall diet
*Limit alcohol intake
*limit purine intake (sweetbreads, liver, kidney, sardine, shellfish)
*limit high fructose corn syrup
*encourage lowfat or non fat dair products, vegetables
weightloss program if overweight or obese
indications for chronic ULT for gout
> 1 sq tophi, radiographic evidence of dmaage attributable to gout OR frequent flares (>/2 /years)
may consider trt if…
hx of >1 attack, but <2 attacks per year
those w. first gout flare w. following characteristics
AND any of these
CKD stage 3
UA> 9 mg/dL
urolithiasis (kidney stones)
if decision is made tht pt needs ult duraing a flare, it shouldbe initiated during a flare
chronic Therapy of gout goals
goal ua level:
what is 1st line trt:
when to montor ua levels:
if therapy not appropriate, what to do ?
how long is therapy and at what dose?
goal serum urate level: <6 mg/dL
allopurinol is 1st line gaent
UA levels should be monitored q 2-5 weeks w. increases in ULT intensity until goal is reached
*increase dose of XOI, add probenecid if appropriate
therapy required to reach goal of <6mg/dL shoul dbe continued indefinately
indication for swtch to pegloticase as chronic ULT
XOI trt, uricosurics, and other interventions failed to achieve goal UA levels, and pt continues to have >/2 flare/yr OR non reslovng tophi
Flare ppx
pps w. antiinflammatory meds should be intiated when ULT is intiated
same agents as for flare trt at diff dose
shold be continued for 3-6 mo.
based on resolution of symptoms and absence of tophi
serum UA lowering therapy PPX
when to initiate:
algorithm (including choices and doses)
when to initiate:
*w. or just prior to initiating ULT
CHOICES:
a)first line
*low dose colchicine 0.6 mg qd or bid OR
*low dose nsaids (ex naproxen 250mg)
b) second line
*low dose prednisone or prednisolone (</10mg/day)+PPI if indicated
*only used if colchicine and NSAIDS both not tolerated, CI, or ineffective
monitor and evaluate gout symptoms while on ULT
*if no signs and symptoms
a) continue ppx for atleast 6 mo!! OR
3mo after achieving target serum urate appropriate for pt (no tophi on physical examination)
*6 mo after acgieving target serum urate appropriate for pt (one or more tophi detected on physical examination)
NOTE: TREAT FOR WHICHEVER DURATION IS GREATER
*if SS of gout (flare in last 3 mo palpable tophi present)
a)continue ppx therapy
epidemiology of Osteoarthritis (OA)
disease of elderly as ppulations age
common: 1/5 ppl have OA
by 2040, 25.9% will have OA expected
reletavily expensive condition
$9233 per person
risk factors for OA
obesity
sex: men at oyungr, female at older
occupations (jobs that ave regular mechanical stress)
participation in certain sportss
joint injury or surgery
genetic predisposition
what is the #1 modifiable risk factor for OA
obesity
OA patho
Under normal conditions, cartilage matrix is subjected to a dynamic remodeling process in which low levels of degradative and synthetic enzyme activities are balanced, such that the volume of cartilage is maintained. In OA cartilage, however, matrix degrading enzymes are overexpressed, shifting this balance in favor of net degradation, with resultant loss of collagen and proteoglycans from the matrix
OA classifications
Idiopathic (primary): no known cause
Secondary (classified by cause)
*note: can also be classified by joint involvement
secondary causes of OA
traumatic (accidents)
gongenital/genetic:
metabolic: pagets disease, wilsons disease, nutritional defficiencies
neuropathic: Charcot arthropathy
HEmatologic: Hemophilia, sicklecell disease
Other: Gout, RA
ACR criteria for Hand OA
hand pain, aching or stifness and 3 or 4 of following treatments
1)hard tissue enlargement of 2 or more of 10 selected joints
2)hard tissue enlargement of 2 or more DIP joints
3)fewer han 3 swollen MCP points
4)deformity of atleast 1 of 10 selected joints
clinical features of hand OA
Signs
signs
bony enlargement of affected joints of affected joints
*heberdens nodes (develop slowly, non painful, lateral and medial aspects of the joint)
*bouchards nodes: same as heberdens nodes, at diff locations
limitation of range of motion
crepitus w. motion
pain w. motion
malalignment and/or joint deformity
Knee OA epidemiology
most common cause of arthritis and chronic disability among older ppl in US
radiographic abnormalities present in >30% persons>65 y.o
symptomatic kknee OA occurs in ~10% of ppl >65 yo
leading indication for >250k total knee arthroplasties in US / year
clnicnal features of knee OA
JOINT PAIN
MORNING STIFFNESS
JOINT INSTABILITY
LOSS OF FUNCTION
OCCASIONAL SYNOVITIS
bowleggednes (vargus)
knock knees (valgus)
ACR criteria for knee OA
clinical classification
knee pain and atleast 3 of following 6 criteria
1. >50 yo
2.stiffness lasting <30 min
3. crepitus (grating sound produced by friction of bone
4.bony tenderness
5.bony enlargement
6. no warmth to touch
*not most sensitive, least
clinical and lab classification if knee OA
clinical and lab classification
knee pain and atleast 5 of following 9 criteria
1. >50 yo
2.stiffness lasting <30 min
3. crepitus (grating sound produced by friction of bone
4.bony tenderness
5.bony enlargement
6. no warmth to touch
- esr <40 MM/HR
- rf<1:40
- Synnovial fluid: clear, viscous, or wbc <2000/mm^3
acr radiographic criteria fro knee OA
atleast 1 of following of 3
*age>50 y,o
*stiffness <30 min
*crepitus
AND osteophytes (detected by radiography)
least sensitivity, most specific (negatives are true negatives)
ACR criteria: HIP OA
HIP PAINand atleast 2 of folowing 3 features
*esr<20 mm/hr
*radiographic femoral or acetabular osteophytes
*radiographic joint space narrowing (superior, axial and/or medial)
89% sensitivity and 91 percent specitivity
clinical featurs of hip OA
hip pain: gradual onset, increases with joint use, relieved (incompletely) with reset
as the disease becomes more severe:
*morning stiffness and pain (up to 30 min)
*pain at rest or at night are common
STRONFEST clinical indicator is pain exacerbated by intern or external rotation of the hip while the knee is in full extension
non pharm treatment of OA considerations
can use more than one modality
consider pt comfort
exercise, braces, etc.
*un
non pharm management of hand OA
storngly recommended
*exercise
*self efficacy and self management programs
*first carpometacarpal (CMC) orthosis
conditionally recommended:
*heat or tpx cooling
*cbt
*acupuncture
*kinesiotaping
*hand orthosis other than CMC
*paraffin
non phar knee OA
storngly recommended
exercise
self efficacy and self management programs
weight loss(if overweight)
Tai-Chi
Cane
Tibiofemoral (TF) brace for TF OA
conditionally ecommended
*heat, tpx cooling
cbt
acupuncture
kinseotaping
balancetraining
yoga
patellofemoral (PF) knee brace for PF OA
radiofrequency ablation
non pharm treatment for hip OA
strongly recommended
exercise
self efficacy and self management programs
weightloss (if overweight)
tai chi
cane
conditonaly recommended
heat tpx cooling
cbt
acupuncutre
balance training
yoga
exercise considerations for OA
duration, intensity, frequency
*unknown
*driven by what pt is comfortable with
pt preference
patient access
possible options
*walking
*stationary bike
*isokinetic(dynamic contraction, speed control), isometric (static tension, maintains strength)
*rsistance training w. or w.o props
*aquatic exercise
Self efficacy and self management programs for OA
multi disciplinary group based on skill building and education
skill building
*goal setting
*problem solving
*positiv thinking
education
*fitness goals
*joint protection
*medication
other therapies for non pharmt trt of OA
Hand orthosis: goes over cmc joint: supporting joint
kinesiotaping: functions similarly to a brace but more flexible in terms of movement. tape supports hand and muscle of hands or knees
parrafin: wax that heats up
braces:
tibiofemoral (TF)
*patellofemoral (PF)
conditionally and strongly recommended against non pharm treatments for OA
knee OA:
TTENS(transcutaneous electrical nerve stimulation (TENS)
conditionally recommened against:
manual therapy (w. or w.o exercise)
massage therapy
modified shoes
wedged shoes
pulsed virbation therapy
hand OA
conditionally recommended against
*iontophoresis
hip OA:
strong recommended against
TENS
conditionally recommended against
manual therapy (w. or w.o exercise)
massage therapy
modified shoes
wedged insoles
pharm therapy for OA considerations
no disease modifying agents for OA
meds are for pain relief
pharm treatment for hand OA
(strongly recommended therapy)SRT:
oral NSAIDS
lowest possible dose thats effective for shortest duration as possible
conditionally recommended therapy (CRT)
topical NSAIDS
IA CCS
APAP
TRamadol
duloxetine
chondroitin
types of non selective nsaids
A)proprionic derived nsaids
*ibuprofen
naproxen
ketoprofen
fenoprofen
oxaprozin
b)acetic acid derived nsaid
indomethacin
diclofenac
ketorolac
etodolac
sulindac
tolmetin
c)fenmates derivatives
*meclofenamate
mefenamic acid
enolic acid derivatives
peroxicam
meloxicam
alkanone derivatives
*nabumetone
pharm trt for knee OA
SRT:
oral NSAIDS
topical NSAIDs
IA CCS
CRT:
APAP
tramadol
duloxetine
topical capsaicin
pharm trt for hip OA
srt:
oral NSAIDS
IA CCS (guided by imaging)
crt:
APAP
tramadol
duloxetine
pharm mgt recommended AGAINSt for hand OA
sra:
biphosphonates
glucosamine
hydrochloROQUINE
methotrexate
tnf inhibitors
il-1 receptor antagonists
cra:
IA hyaluranoic acid
colchicine
non-tramadol opioids
fish oil
vit d
topical capsaicin
pharm mgt recommended AGAINSt for knee OA
sra:
biphosphonates
glucosamine
hydrochloROQUINE
methotrexate
tnf inhibitors
il-1 receptor antagonists
platelet rich plasma
stem cell injection
chondroitin
cra:
IA hyaluranoic acid
IA botulinum toxin
prolotherapy: injection of hypertoinc dextrose
colchicine
non-tramadol opioids
fish oil
vit d
topical capsaicin
pham mgt recommended against forhip OA
sra:
biphosphonates
glucosamine
hydrochloROQUINE
methotrexate
tnf inhibitors
il-1 receptor antagonists
platelet rich plasma
stem cell injection
chondroitin
IA Hyaluronic acid
cra:
IA botulinum toxin
prolotherapy: injection of hypertoinc dextrose
colchicine
non-tramadol opioids
fish oil
vit d
topical capsaicin
overall considerations for trt of OA
consider pt factors
*what has worked in the past?
*what is the pt comfortable doing
*what other conditions does the pt have?
ex: HTN, cv disease, HF, CKD, GI bleeding risk etc.
clinical prsentation of RA
symptoms present for >6 weeks
warmth and swelling over affected joints with or w.o pain
prolonged morning stiffness>30 min
fatigue weakness, decreasedmood, low-grade fever
positive rheumatoid nodules
joint deformity in late disease
joint involvement in RA
MOST COMMONLY EFFECTS small joints (hands wrist, ankles and feet bilaterally
larger weight beighring joint sless commonly effected
lab findings for pts with RA
ANTI-CITRULLINATED PROTEIN ANTIBODIED (acpa): 96% in ra
rheumatoid factor (RF):70-80% in ra
antinuclear antibodies (ANA): ~20% in ra
also…
elevated nonspecific inflammatory markers such as ESR, CRP
synovial fluid analysis wbc1500-25000m//^3
dx of ra
CHALENEGES:
no single tet or physical finding
*early detection is difficult
acr/eular criteria:
*serology/acute phase reactants
*duration of SS
*joint involvement
disease severity evaluation in RA
Disease activity Score
scale 0 to 9.4
high disease activity :>5.1
mod diseasy activity: >/3.2 to </5.1
low disease actiity : >/2.6 to <3.2
remission: <2.6
RA vs OA
age:
onset:
development:
SS:
joint involvement:
joint stiffness duration:
joint pain:
symmetry:
auto antibodies:
age:
*RA: varibale
*OA:>50 y.o
onset:
*RA:VRIABLE
*OA:gradual
development:
*RA: autoimmune
*OA: wear and tear
SS;
*RA: constitutional and joint
*OA: localized to joint
Joint involvement:
*RA:small joints of hands, wrists and feet
*OA: large weight bearing joints
joint stiffness:
*RA:>30 min
*OA:<30 min
joint pain:
*RA:w. use and at rest
*OA:w. use
symmetry
*RA: bilateral
*OA:unilateral
auto antibodies
*RA: present
*OA:none
GOALS OF therapy of RA
treat to target approach w. low disease activity as an acceptabletarget
improve SS of joint pain and stiffness by reducing inflammation
slow disease progressionand prevent joint damage
Non pharm therapy for RA
REST
weight loss
physical and occupational therapy
*assistive devices
*exercise
*physiotheraoy
patient education
*surgery-severe ra
*tendon repair, arhtroplasty, tenosynovecotomy
non disease modifying therapy for RA
NSAIDS
*decrease joint pain and inflammation
*acute ysmptom relief
*adjunct to disease modifying agents
CCS:
*decrease joint pain and inflammation
bridge to disease modifier
*short term high doses or flares
*long term low doses for refractory diseasse
**prefer to ass or switch disease modifier
disease modifying therapy for RA
categories
Conventional synthetic csDMARDS:
*mathotrexate, hydroxychloroquine, sulfasalzine, leflunomide
*others: gold salts, minocycline, CsA, cyclophosphamide, D-penicillamine
biologic dmard
*TNF inhibitors (etanercept, infliximan, adalimumab, golimumab, certolizumab
*non tnf inhibitors (abatacept, rituximab, tocilizumab, anakinra, sarilumab)
targeted synthetic (tsDMARD; JAK inhibitors)
*tofacitinib, baricitinib, upadacitinib
treatment prinicples for RA
INITIATE CSdmards within 3 mo of onset of persistent symptoms
short term CCS for bridging to dmard onset
*guidelines recommendavoind CCS theraoy if possible, however many pts require a short course for symptm relief
step up strategy
*additional dmards when disease burden not adequately controlled
treat to target approach
*remission may not be achievable in all pts
dmard THERAPY algorithm for RA
1)assess disease activity
if pt is dmard naive:
a) low disease activity:
*csdmard monotherapy: HYDROXYCHLOROQUINE (HCQ)
*alternative (selfasalazine>mtx>leflunomide
b)mod-high disease activity
*csmard monotherapy:
MTX
2) is pt at target of low disease activity or remission?
YES:
continue regimen
*must be at traget for atleast 6mo before dose reduction/dmard d/c
continue >/1 dmard due to risk of disease progression
*if d/c, d/c gradually
*if symptoms return, reinitiate dmard
NO:
*if non mtx csdmard monotherapy.. switch to mtx
*if oral mtx not at target-> switch ot sq mtx over addition to another dmard
*if absence of poor prognostic factors-> add csdmard
*if poor prognostic factors-> add bdmard or tsdmard
3) is pt at low disease acivity or remission
YES:
continue regimen
NO:
*optimize above therapy, then: add/switch to bdmard or tsdmard or a diff class
asssess DMARD use for efficacy q3 mo
poor prognostic factors for RA
persistent mod-high disease activity score despite csdmard
high acute phase reactant levels
high swollen joint count
presence of rf and/or ACPA, especially at high levels
presence of early erosion
failure of 2 or more csdmards
csDMARDS
MTX
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
csDMARDS
MTX
indication: 1st line csdmard of choice except in dmard naive pt w. mod-severe disease activity
moa: folate antagonist
dosing: 7.5 mg PO qw titrated to >/15 mg weekly w.in 4-6 weeks
*if unable to tolerate weekly oral dose, split oral doseover 24 hr orswitch to sq
AE:
*NV
*stomatitis
*dizziness/faituge/headache
*pneumonitis/pulmonary fibrosis
*myelosupression
*immunosupression
*hepatotoxicity/inc. lfts
*alopecia
*rash
CI: pregnancy and breastfeeding, liver or renal impairment, immunodeficiency, myelosupression
onset of effect: 1-2 months
considerations:
*folatesupplementation decreases ADR w.o reducing efficacy
csDMARDS
HCQ
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
csDMARDS
HCQ
indication: usually used in combo w. other dmards or as monotherapy for low disease activity
moa: unkown, but inhibits cytokine production
dosing:
*initial: 400-600 mg po daily
*maintenance: 200-400 mg po daily or divided doses
AE:NVD, qtc prolongation, irreversible retinal damage, photosensitivity
CI: ocular disease-dose dependent retinopathy
liver disease
onset of effect:2-4 months
considerations:
*may be used in pregancy
8preferable risk profie compared to other dmards
csDMARDS
sulfasalazine (SSZ)
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
csDMARDS
sulfasalazine (SSZ)
indication: monotherapy or in combo w.other dmards
moa:unkown: acive metabolites (sulfapyridine and 5-asa) responsible for anti inflammatory properties
dosing: 500-1000 mg po daily (up to 3g has been used)
AE: nv abdominalpain, anorexia
headache
reversible oligospermia
rash, puritis, urticaria, blood dyscrasias
CI: sulfa allergy, intestinal or urinary obstruction, renal and caution in hepatic impairment
onset of effect: 1-3 mo
considerations:
*preffered dmard in pregnancy
csDMARDS
Leflunomide (LEF)
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
csDMARDS
LEF
indication: mono or ocmbo w. other dmards
moa:inhibits pyrimidine synthesis->decrease lymphocyte proliferation
dosing:
loading dose: 100 mg PO once daily for 3 days
maintenance dose: 10-20 mg po daily
AE:
NVD
reversible alopecia
rash
peripheral neuroathy
htn
CI: pregnancy and breastfeedings (teratogenicity across genders)-> levels may take months to decrease
*liver disease
onset of effect:1-3 months
considerations:
long t1/2, may be detectable for up to 2 years
*cholestyramine rmoves drugs and its active metabolites
monitoring for csdmards
monitor cbc lfts and scr based on duration of therapy
MTX, LEF, SSZ
<3mo: q2-4w
3-6 mo:q8-12w
>6 mo:q12w
HCQ: none after baseline
additoinal specific drug monitoring:
MTX: r/o pregnancy, chest xray at baseline
HCQ: opthalmologic exam at baseline and q3mo
SSZ: r/o G6PD deficiency at baseline
LEF: r/o pregnancy at baseline
general bdmard considerations for use in RA
geenrally well tolerated but costly
target pro inflammatory cytokines
*TNF-a, IL-1, IL-6, B cells, T cells
when to use based on algorithm: mod-high disease activity despite dmard monotherapy
unable to tolerate / ci TO CSDMARD
adequate trial
:tnfI biologics: 3 mo
non tnfI biologics: 6 mo
TNF-inhibitor subq options
etanercept (Enbrel)
adalimumab (humira)
golimmumab (simponi)
Certolizumab (Cimzia)
TNF-a biologics-sub q options
drug: etanercept (enbrel)
dosing:
use w. mtx:
common ADR:
TNF-a biologics-sub q options
drug:
etanercept (enbrel)
dosing: 50 mg weekly OR 25 mg twice weekly
use w. mtx: w. or w.o
common ADR:pancytpenia, injection site rxn, diarrhea, rash
TNF-a biologics-sub q options
drug: adalimmumab
dosing:
use w. mtx:
common ADR:
TNF-a biologics-sub q options
drug:
dosing:40 mg q2w. if no mtx, 40mg weekly
use w. mtx: w. or w.o
common ADR: sinusitis, urti, antiboy formation, injection site reaction, hadache, rash
TNF-a biologics-sub q options
drug: golimumab (simponi)
dosing:
use w. mtx:
common ADR:
TNF-a biologics-sub q options
drug:
dosing: 50 mg once monthly
use w. mtx: must be w. methotrexate
common ADR: URTIE, nasopharyhgitis, antibody formation, injection site reaction
TNF-a biologics-sub q options
drug: certolizumab
dosing:
use w. mtx:
common ADR:
TNF-a biologics-sub q options
drug:
dosing: 400 mg at 0,2,4 weeks then 200 mg q 2 weeks
use w. mtx: with or without
common ADR: URTI, UTI, antibody formation, dizziness, htn, rash
TNF-inhibitor iv options
Inflixumab (Remicade)
Golimumab (Simponi Aria)
TNF-a biologics- IV options
drug: INFLIXIMAB (Remicade)
dosing:
use w. mtx:
common ADR:
TNF-a biologics- IV options
drug:
dosing: 3mg/kg over /> 2 hrs at 0, 2, and 6 weeks then 3-10 mg/kg q4-8weeks
use w. mtx: must be used with methotrexate
common ADR: URTI, infusion related reactions (premedicate w. antihistamine, APAP, CCS), headache, abdominal pain, antibod formation
TNF-a biologics- IV options
drug: golimumab (Simponi Aria)
dosing:
use w. mtx:
common ADR:
TNF-a biologics- IV options
drug:
dosing: 2mg/kg over 30 min at weeks 0, 4, then 2 mg/kg q8weeks
use w. mtx: preffered w. methotrexate
common ADR: URTI, ALT/AST elevation, HTN, rash, neutropenia, antibody formation
TNF-I Safety concerns
BBW
*risk of malignancy-> lymphoma and other malignancies
*serious infections leading to hospitaliztion or death-> opportunistic fungal viral, and bacterial functions
May lead to exacerbations of
*MS/MS like symptoms
*SLE/ SLE like symptoms
*HF-> avoic in NYHA class III or IV of LVEF<50%
Latent TB and HepB infections-> screen all pts for tb and hepatitis b before intiaition
non TNF-I biologics- list of subq options
abatacpt (orencia)
sarilumab (kevzara)
toclizumab (Actemra)
Anakinra (Kinret)
non -TNF-a biologics- sq options
drug: abatacept (Orencia)
dosing:
cell target:
common ADR:
non -TNF-a biologics- sq options
drug:
dosing: 125 mg once weekly
cell target: t cells
common ADR: URTI, headache, nasopharyngitis, nausea
non -TNF-a biologics- sq options
drug: sarilumab
dosing:
cell target:
common ADR:
non -TNF-a biologics- sq options
drug: sarilumab
dosing: 200 mg q2w
cell target: IL-6 inhibitor
common ADR: URTI, UTI, injection site erythema, neutropenia, increased LFTs, antibody formation
non -TNF-a biologics- sq options
drug: toclizumab
dosing:
cell target:
common ADR:
non -TNF-a biologics- sq options
drug:
dosing: <100 kg: 162 mg qow (increase to weekly as tolerated)
>/100 kg: 162 mg
cell target: IL-6
common ADR: URTI, nasopharyngitis, headache, HTN, increased LFTs, increased lipids
non -TNF-a biologics- sq options
drug: ANAKinra (kineret)
dosing:
cell target:
common ADR:
note:
non -TNF-a biologics- sq options
drug:
dosing: 100 mg once daily
cell target: IL-1
common ADR: URTI, rash, pyrexia, influenza like illness, gastroenteritis, vomiting, antibody formation
note: limited use given reduced efficacy compared to other bdmardS
considertionf for non tnf-i
all used as monotherapy or w. non biologic dmard
non -TNF-a biologics- IV options
drug: abatacept (oriencia)
dosing:
cell target:
common ADR:
note:–
non -TNF-a biologics- IV options
drug:
dosing: wieight based dosing at 0,2, and 4 weeks, then q4 weeks
cell target: t cells
common ADR: URTI, nasopharyngitis, nausea, htn, infusion reaction
note:–
non -TNF-a biologics- IV options
drug: rituximab
dosing:
cell target:
common ADR:
note:
non -TNF-a biologics- IV options
drug:
dosing: 1g at 0, 2, weeks (one cycle); may repeat cycle q16-24 weeks based on response
cell target: anti-cd20 antibody
common ADR: URTI, UTI, nasopharyngitis, PML, infusion reactions (premedicatew. antihistamine, apap, ccs)
note:
*served for those who fail other bdmard or w. hx of lymphoproliferative disorder
*should be used w. mtx, other options may be monotherapy or be used w. other NONBIOLOGIC dmards
Monitoring for bDMARDS
All patients should be screened for latent tb AND hep B prior to initiation
Baseline:
*TNF-I: CBC, LFTs(infliximab)
*Abatacept: CBC and done periodically thorughout treatment
*Rituximamb: CBC and done w. each dose
*IL-1 I: CBC
*il-6: CBC, ANC, LFTs, flp
after 4-8 weeks
*TNF-I: LFTs(infliximab)
*Abatacept: –
*Rituximamb–
*IL-1 I–
*il-6: cbc, lftS, flp
Q3mo
*TNF-I: –
*Abatacept: –
*Rituximamb: CBC
*IL-1 I: CBC
*il-6: cbc, lftS,
*TNF-I: –
*Abatacept: –
*Rituximamb–
*IL-1 I–
*il-6: flp
JAK inhibitors
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
indication:
*mod-high disease asctivity depsired dmard monotherapy
*unable to tolerate/ ci TO CS DMARDS
moa: inhibit janus kinase (jak( ENZYMES WHICH BLOCKS TRANcription of inflammatory genes
dosing:
AE:
CI:
onset of effect:
considerations:
*BBW: risk of opportunistic infections, lymphoma and malignancies, thrombosis, including dvt, PE, arterial thrombosis
*daily oral administration
*used alone or in combo w. mtx or NONbiologic therapY
JAK inhibitor examples
Tofacitinib (Xeljanz)
dose: IR: 5 mg BID, XR 11 mg daily
ADR: increased hdl and ldl, headahce, UTI, URTI, GI perforation, anemia, neutropenia, skin cancer, PE, infections
Baricitinib (olumiant)
dose: 2mg daily
ADR: inc ast/alt, nausea, herpes zoster and othr infections, gi perforation, thormbosis, infections
upadacitinib (Rinvoq)
dose: 15mg daily
ADR: inc hdl/ldl, tc, and a/alt, nausea, urti, skin cancer, gi perforation, thormbosis, anemia, neutropenia, infections
treatment considerations foR RA
what is 1st line?
when to add when mono therapy not working?
1ST LINE: MTX MONOTHERAPY DMARD-NAIVE PT W. MOD-SEVERE DISEASE ACTIVITY
*recommended over lef, bdmard, tsdmard, or trippletherapy for dmard naive pts
addition of csdmard, bdmard, or ts dmard is preffered over tripple therapy
swithcing to a bdamrd or tsdmard of a diff class if recommneded over switching to an agent in same class
reaching trt target for RA
continue treatment for >/6 mo before dose reduction or dmard d/c
continue atleast 1 dmard at therepeutic dose lifeling to prevent relapse or disease progression
if d/c dmard, taper slowly to avoid a flareup
if symptoms return, re-initiate dmard
comorbities to ocnsider in RA
active tb: aboiv biologics or jaki
latent tb: may use biologics after one month of starting tb trt
hep b: use caution w. biologics and jaki, screen first
pregnancy: avoid mtx and lef
HF: avoid tnfi in nyha III-Iv
*non tnf-i are preffered
liver disease: avoid mtx or lef
*use cuaition w. hcq and ssz
kymphoproliferative disordr: prefer rituxumab
vaccinations in pts w. RA
2 weeks Before dmard therapy, pneumococcal, influenza (inactive) hep b, hpv, and live herpez zoster virus
for biologic agents, live vaccines (such as live herpes zoster) should not be given
two forms of Lupus
SLE: systemic: can affect all organ systems
*malar rash (butterfly rash)
Discoid: primarily effects skin
*discoid rash: can lead to permamanent scarring and alopecia , can also occur inside he mouth
SLE epidemiology
women 9x more likely during child bearing years
most common age child bearing age: 16-55 y.o
black and hispanic 4x mor likely
etiology of sle
unkown
genetics: risks for offspring w. mothers having sle
environment: UV light #1 environmental factor, stess, smoking, medications like hydralazine and procainamide
Viruses: e.g EBV
Hormones: high levels of estrogen (higher sle risk in oral contraceptive users , and inc in post menopausal women given estrogen
Prolactin:
decreased sle risk associated w. breastfeeding
phases of sle
Preclinical Phase
preclinical:
*asymptomatic
dysregulation of cellular apoptosis
increass in apaoptosis
clearance deficiencies due to macrophages:
a
*nuclea autoantigens presnt to:
*dendritic cells: IFN a factories
*b cells autoantibodies
*something triggers this to
causing impaired tolerance:
*precipitting facrots/initial insult
*activated dendritic cells present auto antibodies to communicate w. b cells
SLE patho
clinical phase aka SLE specific phase
ab self bind to form antibody immune complexes
these immune complexes deposit in vasculatrue and suceptible tissues (skin, kidney etc.
it is a type III hypersensitivity reaction
8neutrophils complement activta rto destroy immune complexes, IFN, TNF , immune reaction leads to tissue damage, inability to clear complexes efficiently, causing …
INFLAMMATION
basic picture of patho sle
suceptibility(geentics, complement levels, hormone levels) +environmental insult causes..
autoimmune proliferation
leads to…autoantibody production
SLE timeline
extremely variable
SLE presentation
variable manifestations due to effects on any organ system
ACR DX CRITERIA
most common presentation, woman of child bearing rage presenting w. rash, fever, arthralgias
acr DX CRITERIA FOR sle
only need 4/11
*has 85% sensitivity
*95% specificity
SOAP
BRAIN
MD
SOAP :SLE
S: SEROSITIS:
*pericarditis or pleuritis (pain rub/effusion
O: oral ulceration
*typically painless
Arthritis:
non erosive, usually case 2+ peripheral joints
Photosensitivity
*malar rash but any rash
BRAIN: SLE
BLOOD DIsorders
*meolytic anemia, or leukopenia, or lymphopenia, or thrombocytopenia
Renal involement
*proteinuria or cellular casts
Antinuclar antibodies (ANA)
*hallmark serological signs of sle
immunologic disorder
*anti smith nuclear antigen
*anti phospholipids
*anti-dna ab
Neurologic disorder
*seizure
*psychosis
MD sle
malar rash
discoid rash
serological testing for sle dx
1.ANA testing
low positive predictive value
high neg predictive value (helpful for excluding lupus, but now 1000% especially if clniical featurs are present
2.rim immunofluroessence
3.anti-dsDNA ab
4.anti-sm ab
antiphospholipid syndrome and sle (APS)
hypercoagulable sate , autoimmunity
~50% of sle pt are aPL+
aPl(+) PLUS thrombotic event=APS
*anticardiolipin and lupus anticoagulant( blood thinning effects in vitro, coagulating effects in vivo)
important because: greatly increases risk fo rclotting event, inc morbidity and mortality. must lower a risk ofevent, including dvt, stroke, and neurologic manifestations
aps associated w. premature births, eclampsia, and stillbirths
Lupus nephritis
epidemiology
patho
dx
SS
was most common cause of death in sle pts
(now its infection)
in ~35% of ppl at time of dx
formation of immune complexes and lodging into glomeruli or forming in flomeruli, causing inflammation
*6 classes
dx:
persisent proteinuria and or cellular catss
renal biopsy and histology to confirm
SS: fomay urine
*peripheral edema
*concamiant htn
*class III-VI are more severe and require immunosupression or preparation for transplant
considerations for MEDS USED TO TREAT sle
TOPICALS
dose more important than drug
choose appropriate drugs for where rash i s located
cousel an dproper use and handeling
steroid ocncerns , use topical cni (TACROLIMUS)
MEDS USED TO TREAT sle
NSAIDS
for pain and inflammation caused by various sle symptoms
acute or chronic
GI, cardiac, renal, concerns
monitor: kidney function, cbc
aspirin may be used to prevent clots in sle pts. counsel pt aspirin must be taken atleast 1 hr before nsaid
considerations for topical steroi duse for rashes in sle
location of rash
sseverity of rash
potency os steroid
CYCLIC application
medium (cream vs lotion v gel)
pharm treatment forSLE
HCQ
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
indication: long term management of SLE and DLE
8most utuilized in lupus
moa:
dosing:
*supress: 400 mg QD-BID
maintenance: 200-400 mg QD
AE: flu like symptoms, ocular toxicity (inc risk include incr doses, length of therapy, ckd,) allergic skin reactions refractory to antihistamines, skin an dhair pigmintation changes, hematologic changed (agranulocytosis, aplastic anemia, thrombocytopenia, pancyotpenia), gi upset, myopathies/palsies/cns effects,
rare: cardiomyopathy and hearing loss
CI:
onset of effect: 2-4 months to work. nsaids and steroids can be used to control ymptoms. adequate trial period 6 months
considerations:
*rudces skin rashes, major organ involvement, mortality over time, good in pregnant women
*adequate trial atleast 6 months
HCQ monitoring
CBC, liver function, kidney function at baseline and periodically throughout therapy
Ocular toxicity mointoring: at baseline, then at 5 years, then annually therafter
if pt a increased risk for qtc prolongation, do ekg at baseline and if clinically indicated
Systemic Glucocorticoids in sle treatment
rapid symptom relief
can even use pulse iv stroids for false relief
adjunctive trt reserved for
*mod-sev initial presentation
*organ threatening or life threatening sle
inadequate response to hcq/nsaid
poor qol w.o it
dose:
A)supressive dose: prednisone 20-60 mg/d
IV pulse:
B)TAPER 10-20%Q5-7 DAYS until its minimized to a daily dose of </7.5 mg/d or equiv
c)ideally, taper off ocpletely
AE: hpa supression, osteoporosis, hyperlipidemia, moon faces, amenorrhea, immosupression, obesity, echymosis etc.
belimumab (benlysta)
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
indication:
* adjunctive therapyused in non-active cns, ANA+ SLE
*first mAb fda approved for sle
*adjuncive therapy for incomplete response to HCQ/NSAID/STEROID
*fda approved as adjunctive therapy for lupus nephritis
moa: b lymphocyte stimulator antagonist ( blymphocyte stimulator activates, stimulates and prevents normal apoptosis of b cells)
dosing:
AE: allergic rxn, infusion rxn, DEPRESSION/suicidality, PML(brain infection tht is rare)
CI: psychosis or dementia, not tested for safety or efficacy in these ppl,
onset of effect: 2-4 months
considerations:
given IV or SQ
do not use live vaccines
Anifrolumab (Saphnelo)
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
indication: adjunct to standard therapies in SLE
moa: interferon antagonist (reduce immune cell recruitment and allowsymptomatic improvements, stbializes organ disease
dosing: IV infusionq4w
AE:
CI:
onset of effect:
considerations:
not indicated in active LN or cns DISEASE
immunosupressants indications in sle trt
poor symptom control after hcq/steroids
indicated for organ threataning sle, mainly lupus nephirtis (often used in combo w. steroids
ex: azothioprine, cyclophosphamid, cyclosporine, methotrexate, mycophenolate
immunosupressants use in sle trt
mTX
indication: CONCAMINANT ra or main problem of arthritis
more effective than AZA
ae: bone marrow supession, gi toxicity, hepatotoxicity, nephortoxicity
immunosupressants use in sle trt
azathioprine (AZA)
indication: second line after steroids for a more moderate disease course
safest for pregnancy
ae: bone marrow supression, n/v
immunosupressants use in sle trt
micophenolate mofetil/sodium (mmf)
indication: proliferative LN, second line for membranous ln
also usful in non renal disease
ae: gi side effects
risks of hematological, cv, teraogenicity
immunosupressants use in sle trt
cyclophosphamide
was LN gold standard
incrediby toxic
ex: organ threatening dardiopulmonary, renal, or neuro disease
can cause permament infertility
immunosupressants use in sle trt
cyclosporine
useful in membranous LN.
can cause HTN
immunosupressants use in sle trt
rituximab
not formally indicated for sle, but can be used in pts who are refractory to everything else
immunosupressants use in sle trt
calcineurin inhibitors
most commonly tacrolimus, for proliferative LN alone or in combo w. MMF
Voclosporin
HCQ
indication:
moa:
dosing:
AE:
CI:
onset of effect:
considerations:
indication: adjunct to immunosupressants to LN
moa:
po calcineurin inhibitor (decrease cytokine production, lymphocyte proliferation.
dosing: PO
AE: nephrotoxicity if eGFR<45
CI: do not use w. cyclophosphamide
onset of effect:
considerations:
BBW for infections and malignancies
3a4 interactions, including grapefruit
pharm treatment for sle condierations
treat to target
shared decision making btw pt and md
non pharm management for sle
trigger avoidance
*sunscreens(broad spectrum)
*avoid photosensitizing agents
prevent/eradicate infection
*treat agressively
*immunizations/vaccines
EULAR sle pharm algorithm
mild sle
1s line: HCQ or GC PO/IM
refractory: HCQ or/+ GC PO/IM/, MTX/AZA
moderate
1st line: HCQ or GC PO/IM, MTX/AZA, CNI, MMF
refracory: HCQ or GC PO/IM, Bel, CNI, MMF
Severe:
1st line: HCQ or GC PO/IM, MMF, CYc
REFRACORY: HCQ or GC PO/IM, cyc, rtx
eular target goals for sle
low disease activity
SLEDA<=4; HCQ-PREDNISONE <=7.5 MG/D
immunosupressives (in stable doses-well tolerated)
adjunct therapy to sle harm treatment
sun protection
vaccinations
exercise
no smoking
body weight
blood presure
lipids
glucose
anti platelets
anticoags (in aPL+ pts)
guideline recommendations fo rskin disease in sle
refactory/severe sle agents
methotrexate
mycophenolate
AZA
*pregnant pts
Cyclophosphamide
*rserve for organ threatening
*rescue therapy in non responds
adjunctive therapy
belimumamb
adjuntive to immunosupressants
useful in adjunct to help lower steroid doses
frequent relapses despite hcq/steroid
in addition to steroind therapy (not inplace of it
iv or sc available (sc adults only
not indicated in active cns disease
basic lupus nephritis care
induction: immunosupressant (MMF or CYC) PLUS steroid
remissoin: taper doses and switch immunosupressants if needed
Class III-IV LN trt
A)intial:
GC+MMF or
GC +lowdose IV CY or
GC+MMF+TAC
**severe: all above optoins and GC+high dose IV CY
B) assess response in 3-12mo.
(target goal is reductio in proteinureia <=25% of stable gfr at first 3 mo., <=50% reduc by 6 mo, and < 0.5-0.7 g/24hr of proteinuria at 12 mo.
*Yes: add MMF or AZA w. no or low dose GS
*if non responding disease or relapses: switch to alternative inductio therapy or add TAC to MMF or rituximab. consider repeat kidney biopsy
class V lupus nephritis treatment
Upr<3 gr/24hr
*RAAS blockade
*consider GC+MMF
Upr >3gr/24hr
*RAAS blockade
*GC+MMF
B) assess response in 3-12mo.
(target goal is reductio in proteinureia <=25% of stable gfr at first 3 mo., <=50% reduc by 6 mo, and < 0.5-0.7 g/24hr of proteinuria at 12 mo.
Yes: continue same trt w. gradual tapering
no: GC+MMF (alternative: IV CY or cni)
RESPONCE AT 3-12 MONTHS?
yes: continue
no: CNI monotherapy or add MMF or high done iv cy or rituximab
other LN care points
use ace/arb in pt who have glomerular disease and
*persistant proteinuria (>/ 0.5g/24hr and or
*htn (target <130/80 mmg
use statin therapy in ldl>100
Pregnancy and sle
pregnancy risk stratification should occur ealy after dx of sle
*HCQ
not associated w. congenital malformations.
inc risk of flair if dc during pregnancy
nsaids
*unsafe in 3rd smeester shbut should avoid anyway
*manage pain with apap
topical steroids
LN in pregnancy trt
mild: hcq/aza
clinicaly active ln:
non fluronated oral steorid can be used
*aza *max dose 2mg/kg/day) if necesary to control ln
PRETERM DELIVERY CONSIDERED (AFTER 28 WEEKS) IF LN highly active
trt of APS (+) or APS
aPL+ w. no event
not pregnant:
daily low dose aspirin(LDA) (81mg)
*reserve for pt w. cv risk
pregnant:
*LDA +/- lmwh
APS
not pregnant
a)arterial: warfarin INR 3-4
b)venous: warfarin INR 2-3
monitoring for sle and followup
SS: q3-6 mo at office visits
adverse drug events
q6mo or less often
UA
BMP
CBC
lipid panel
serologic disease markers
