4. Patient’s story:
• My knee hurt me so much last night, I woke
up from sleep. It was fine when I went to bed.
Now it’s swollen. It’s the worst pain I’ve ever
had. I’ve had problems like this before in the
same knee, once 9 months ago and once 2
years ago. It doesn’t bother me between
times.
5. Novice resident’s presentation:
• My next patient is a 54-
year-old white man with
knee pain. It started last
night. He does not report
any trauma. On
examination, his vital signs
are normal. His knee is
swollen, red, and tender to
touch. It hurts him a lot
when I test his range of
motion. He’s had this
problem twice before
Expert resident’s presentation:
• My next patient is a 54-
year-old white man with a
sudden onset of pain in his
right knee that awakened
him from sleep. He does not
report any trauma and was
essentially asymptomatic
when he went to bed. His
history is remarkable for
two episodes of similar,
severe pain 9 months and 2
years ago. He is pain-free
between episodes. He is
afebrile today
7. Novice resident’s response:
• It could be an infection. It
could be a new onset of
rheumatoid arthritis. It
could be Lyme disease.
Since he doesn’t recall
falling, I doubt it’s an injury.
I don’t know whether
osteoarthritis ever presents
like this, but he does have a
history of knee pain
Expert resident’s response:
• The patient has acute gout. He has
had multiple discrete episodes with
abrupt onset of extremely severe pain
involving a single joint with evidence
of inflammation on examination.
Before all his episodes, he is
asymptomatic. I would have expected
gout to affect the first
metatarsophalangeal joint, but it can
present in the knee. Nothing suggests
any ongoing, chronic problem in the
knee. I don’t see any portal of entry to
suggest acute infectious arthritis and
he looks quite well for that. His other
joints are normal on examination. I
doubt that he has a flare-up of
osteoarthritis with pseudogout or a
systemic, inflammatory arthritis such
as rheumatoid arthritis
10. The rationale for early management
• Several studies have shown that a delay in
treatment commencement is associated with
poorer outcomes.
• First assessment of patients with symptom
duration ≥12 weeks was associated with a 1.3-
times higher rate of joint destruction
• Hazard ratio of 1.87 for not achieving
DMARD-free remission.
11. Window of opportunity
The concept of a ‘window-of-opportunity’
suggests that there is a limited period early in
the course of the disease when the disease
process can be altered or maybe even
reversed with a complete return to normality.
The start of treatment with DMARDs during
this period may have a much greater effect in
halting disease progression and make a real
difference in the outcome of the patient than
treatment at a later stage
14. Why is it important to measure?
• Currently, treatments are available that can
bring about complete disease remission.
• To be able to provide optimal treatment to a
patient it is important to know about the
actual disease activity.
• Regular disease activity assessments are
necessary to judge if this goal has been
reached or whether adjustments to treatment
need to be made.
19. Frequency of monitoring
• The minimum frequency of monitoring for
implementing effective treatment during the
active phases of the disease is 3-monthly.
When a patient is in persistent remission, this
can be reduced to 6-monthly follow-ups.
25. Pre-treatment screening
• Clinical examination: exclude
infections, malignancy < 5
years, congestive heart failure
• Patient education
• Exclude pregnancy
• Check for compliance with
vaccination plan. Vaccination
according to
recommendations
• Laboratory tests for CBC, liver
function, creatinine, fasting
glucose and lipid profile
• Serology for HIV, HBV and HVC
(for some countries only if risk
factors)
• Serum protein electrophoresis
• Antinuclear antibodies, and if
positive, anti-DNA antibodies
• Exclude active or latent
tuberculosis and treat
according to local guidelines
• Chest X-ray examination
• Oral hygiene/stomatology
assessment (for some centres)
26. Contraindications
• Active and/or chronic
infections.
• Past history of severe or
bad/untreated infection
(tuberculosis +++)
• Hypersensibility to the
active substance
• Demyelinating diseases
and/or retroorbital
optic disease
• Neoplasia* or
hemopathia < 5 years
• Congestive heart failure
(NYHA class III/IV and
ejection fraction ≤ 50 %)
• Pregnancy and/or
breast feeding
• Live attenuated
vaccines
27. Therapeutic response evaluation
• MTX, LEF 3 months
• SSZ 3-4 months
• HCQ 2-4 months
• 3 months for etenercept, adlimumab,
golimumab and certolizumab.
• 4th infusion of infliximab.
• 3 to 6 months for rituximab, abatacept,
tocilizumab and anakinra.
28. Interruption before scheduled surgery
required (medium-high septic risk)
• Infliximab 4-8 weeks
• Etenercept 2-4 weeks
• Adlimumab, Golimumab
and Certolizumab 8-10
weeks .
• Rituxizumab 20-24 weeks
• Abatacept 8-12 weeks
• Tocilizumab 10-12 weeks
• Anakinra 1-2 weeks
• MTX not needed in
routine orthopedic
surgeries, 15 days
• LEF needs washout before
septic sugeries
• SSZ not needed 1-2 days
in case of interference
with drugs or
hepatotoxicity
• HCQ not nesessary
29. Targeted synthetic DMARDs
(tsDMARDs)
• tsDMARDs currently available in the treatment
of RA are Janus-kinas (JAK) inhibitors.
• JAKs are a family of non-receptor protein
tyrosine kinase that affect intracellular
signalling through their association with
transcription factors known as signal
transducer and activator of transcriptions
(STATs)
• Tofacitinib (Xeljanz®) is a pan-JAK inhibitor
34. Use of antirheumatic drugs before pregnancy
and during pregnancy and lactation
• csDMARDs‡ proven compatible with
pregnancy are hydroxychloroquine,
chloroquine, sulfasalazine, azathioprine,
cyclosporine, tacrolimus and colchicine.
• csDMARDs‡ methotrexate, mycophenolate
mofetil and cyclophosphamide are teratogenic
and should be withdrawn before pregnancy.
35. Use of antirheumatic drugs before pregnancy
and during pregnancy and lactation
• bDMARDs¶ continuation of tumour necrosis
factor (TNF) inhibitors during the first part of
pregnancy should be considered. Etanercept and
certolizumab may be considered for use
throughout pregnancy due to low rate of
transplacental passage.
• bDMARDs¶ rituximab, anakinra, tocilizumab,
abatacept, belimumab and ustekinumab have
limited documentation on safe use in pregnancy
and should be replaced before conception by
other medication.
36. Vaccination for patients with RA
• Patients with RA are at higher risk of developing
infections.
• Humoral response to vaccination can be
decreased by DMARDs, mainly by biological
agents.
• Considering rituximab as an example, vaccination
should be performed at least 6 months after the
previous course and 4 weeks before the next one.
• The administration of live attenuated vaccines in
immunosuppressed patients has a potential risk
of severe infection
37. Systemic consequences of the
inflammatory process
• Amyloidosis
• Atherosclerotic disease in patients with
inflammatory arthritis and systemic lupus
erythematosus.
• Anemia of Chronic Disease
39. Conclusion
• What mind doesn’t know eyes don’t see.
• Increase your horrizon.
• Keep up with the changing trends in your
field, CRISPR, Target Specific Medicines and
Monoclonal Antibodies will be the future of
medical sciences.
was a quotation that my teachers used to often recall during my medical student days, to emphasize the fact that without study and acquisition of knowledge one would miss many clinical signs and clues
M
Danish study: the overall, fully adjusted incidence rate ratio of MI in patients with RA was 1.7 (95% CI 1.5 to 1.9), the same as that found in patients with diabetes 1.7 ( 95% CI 1.6 to 1.8)
