Rheumatologic therapies

Question 1

What are some risks/disadvantages of disease modifying antirheumatic drugs?

Answer 1

dose creep- you may have to raise doses over time
lymphoma risk of treatment
infection risk
risk of progressive multifocal leukoencephalopathy
biologics can’t be combined safely
avoid live vaccines

Question 2

Methotrexate: dosing considerations, mechanism

Answer 2

weekly dosing safer than daily
works by inhbiting DHFR (dihydrofolate reductase): inhibits purine synthesis
inhibits AICART: incr. relase of anti-inflammatory adenosine (but can be bad for asthma- adenosine is a bronchoconstrictor)

Question 3

Risks of methotrexate

Answer 3

cirrhosis (very rare)
pneumonitis (rare)
oral sores and scalp hair loss
lymphoma
psoriasis
(does not interact with NSAIDs)

Question 4

limitations of methotrexate, onset of action

Answer 4

takes 4-6 wks to see effect
does not control nodules in RA
does not control central arthritis, so less useful for pts with seronegative spondylarthropathies
requires monitoring of CBC, creatinine, and liver function tests

Question 5

Advantages of methotrexate

Answer 5

reduces mortality in RA
good for SLE
good for maintenance for vasculitis but not for induction treatment

Question 6

hydroxychlorquine: usage considerations (what monitoring is required, interactions, onset of action)

Answer 6

weak, but safe
often used in combo with other drugs
requires annual eye exam to look for retinal damage- mostly medico-legal
4-6 months for onset of action

Question 7

hydroxychloroquine MOA

Answer 7

interferes with antigen progcessing (TLR9)

Question 8

uses of hydroxychloroquine

Answer 8

malaria, RA, SLE (helps keep a lid on the disease- first line)

Question 9

sulfasalazine MOA

Answer 9

AICART inhib leads to release of adenosine (anti-inflammatory)

Question 10

sulfasalazine: usage considerations (what monitoring, interactions, onset of action)

Answer 10

must do G6PD screen before use
then monitor CBC every quarter
6-8 wks before you see a good effect

Question 11

risks of sulfasalazine

Answer 11

rashes, pancytopenia, bloating

Question 12

uses of sulfasalazine

Answer 12

RA, colitis in IBD, peripheral arthritis of seronegative spondies

Question 13

Azathioprine: MOA

Answer 13

prodrug for 6-mercaptopurine that is a purine analog that inhibits purine metab

Question 14

Azathioprine usage considerations (what monitoring, interactions, onset of action)

Answer 14

several weeks to take effect
requires monthly CBC
metabolism inhibited by allopurinol

Question 15

azathiprine risks

Answer 15

allergic hepatitis (rare, more likely with nausea/vomiting and/or dehydration), lymphomas, autoimmunity/allergy

Question 16

uses of azathioprine

Answer 16

transplant recipients, RA, SLE, myositis, vasculitis maintenance,

Question 17

cyclosporine MOA

Answer 17

calcineurin inhbitor. prevents NFKB activity in nucleus

MOSTLY anti-Tcell effects

Question 18

side effects of cyclosporine

Answer 18

dose related

may cause HTN, then renal insuffiency- must stop once renal insufficiency develops (only useful for a few yrs)

Question 19

cyclosporine usage considerations: interactions, onset, uses

Answer 19

6-8 wks
usually used with methotrexate
RA, SLE, chronic urticaria

Question 20

TNF alpha inhibitors: uses and onset of benefit

Answer 20

takes a few weeks
used for RA and seronegative spondies (single best treatments)
reduces RA mortality
not useful for CT disease or vasculitides
most effective in combo with methotrexate

Question 21

TNF-alpha inhibitors: monitoring and risks

Answer 21

incr. TB risk- check PPD

histoplasmosis risk increased

Question 22

TNF-alpha inhibitors contraindications

Answer 22

CHF, MS, active infection

Question 23

TNF-alpha inhibitor types

Answer 23

enbrel: fixed dose and can up-regulate T cell cytokine response
infliximab. remicade: indicated for use with methotrexate

Question 24

rituximab: MOA, monitoring/considerations, time to response, risks

Answer 24

anti-CD20. ppl usually ok with low b cells
plasma cells survive
response seen within days
must premedicate with steroids and acetaminophen to prevent severe infusion reactions
risk of PML (progressive multifocal leukoecephalopathy

Question 25

rituximab uses

Answer 25

RA, Wegener’s, possibly SLE/sjogrens