Clinical case 1

A 55 year old Caucasian female smoker is referred to your clinic with a diagnosis established elsewhere of rheumatoid
arthritis with no benefit from her current therapy of non-steroidal anti-inflammatory drugs. Her history confirms the
presence of symmetrical arthralgia, joint swelling and fatigue of 5 months duration. On examination, she has 8 swollen
joints (right MCP2-4, PIP3, elbow, left MCP2,3, PIP3, both knees) and exhibits 10 tender joints (including feet). Further
investigations in your clinic reveals a positive RF, CRP of 35mg/l, ESR of 55 mm/h, and a DAS28 of 6.46. X-Rays of the
hands and feet depict erosive disease in MCP2, and MCP3 bilaterally. No other significant issues arise in the past
medical history. She is not on any medications beyond her NSAID.

1. What treatment option should be the first choice in the above setting?
a. methotrexate
True. DMARD therapy should be started upon diagnosis of rheumatoid arthritis to reduce disease activity and control
joint damage. Early treatment and tight monitoring of disease activity are fundamental to achieve better outcomes. Due
to its efficacy and safety profile methotrexate is nowadays considered the preferred DMARD to be initiated at diagnosis.
Sulphasalazine and other synthetic DMARDs are generally positioned as alternatives to MTX in case of intolerance or
contraindication. There is no prescribed starting regime for DMARD in RA. Most authorities will recommend
methotrexate, or a combination of DMARDs based on methotrexate. Early data are emerging for the introduction of a
biologic agent from the outset in selected patients with particularly bad prognostic markers. However, this patient was
clearly undertreated and will likely benefit from methotrexate treatment. Starting a biologic upon diagnosis will over treat
a significant number of patients. Corticosteroids may be useful in reducing inflammation rapidly and have been shown to
retard erosion, but they should not be used as the only DMARD unless exceptional circumstances prevail.
b. sulphasalazine
False. DMARD therapy should be started upon diagnosis of rheumatoid arthritis to reduce disease activity and control
joint damage. Early treatment and tight monitoring of disease activity are fundamental to achieve better outcomes. Due
to its efficacy and safety profile methotrexate is nowadays considered the preferred DMARD to be initiated at diagnosis.
Sulphasalazine and other synthetic DMARDs are generally positioned as alternatives to MTX in case of intolerance or
contraindication. There is no prescribed starting regime for DMARD in RA. Most authorities will recommend
methotrexate, or a combination of DMARDs based on methotrexate. Early data are emerging for the introduction of a
biologic agent from the outset in selected patients with particularly bad prognostic markers. However, this patient was
clearly undertreated and will likely benefit from methotrexate treatment. Starting a biologic upon diagnosis will over treat
a significant number of patients. Corticosteroids may be useful in reducing inflammation rapidly and have been shown to
retard erosion, but they should not be used as the only DMARD unless exceptional circumstances prevail.
c. leflunomide
False. DMARD therapy should be started upon diagnosis of rheumatoid arthritis to reduce disease activity and control
joint damage. Early treatment and tight monitoring of disease activity are fundamental to achieve better outcomes. Due
to its efficacy and safety profile methotrexate is nowadays considered the preferred DMARD to be initiated at diagnosis.
Sulphasalazine and other synthetic DMARDs are generally positioned as alternatives to MTX in case of intolerance or
contraindication. There is no prescribed starting regime for DMARD in RA. Most authorities will recommend
methotrexate, or a combination of DMARDs based on methotrexate. Early data are emerging for the introduction of a
biologic agent from the outset in selected patients with particularly bad prognostic markers. However, this patient was
clearly undertreated and will likely benefit from methotrexate treatment. Starting a biologic upon diagnosis will over treat
a significant number of patients. Corticosteroids may be useful in reducing inflammation rapidly and have been shown to
retard erosion, but they should not be used as the only DMARD unless exceptional circumstances prevail.
d. biologic agent
False. DMARD therapy should be started upon diagnosis of rheumatoid arthritis to reduce disease activity and control
joint damage. Early treatment and tight monitoring of disease activity are fundamental to achieve better outcomes. Due
to its efficacy and safety profile methotrexate is nowadays considered the preferred DMARD to be initiated at diagnosis.

Sulphasalazine and other synthetic DMARDs are generally positioned as alternatives to MTX in case of intolerance or
contraindication. There is no prescribed starting regime for DMARD in RA. Most authorities will recommend
methotrexate, or a combination of DMARDs based on methotrexate. Early data are emerging for the introduction of a
biologic agent from the outset in selected patients with particularly bad prognostic markers. However, this patient was
clearly undertreated and will likely benefit from methotrexate treatment. Starting a biologic upon diagnosis will over treat
a significant number of patients. Corticosteroids may be useful in reducing inflammation rapidly and have been shown to
retard erosion, but they should not be used as the only DMARD unless exceptional circumstances prevail.
e. sulphasalazine and hydroxychloroquine combination
False. DMARD therapy should be started upon diagnosis of rheumatoid arthritis to reduce disease activity and control
joint damage. Early treatment and tight monitoring of disease activity are fundamental to achieve better outcomes. Due
to its efficacy and safety profile methotrexate is nowadays considered the preferred DMARD to be initiated at diagnosis.
Sulphasalazine and other synthetic DMARDs are generally positioned as alternatives to MTX in case of intolerance or
contraindication. There is no prescribed starting regime for DMARD in RA. Most authorities will recommend
methotrexate, or a combination of DMARDs based on methotrexate. Early data are emerging for the introduction of a
biologic agent from the outset in selected patients with particularly bad prognostic markers. However, this patient was
clearly undertreated and will likely benefit from methotrexate treatment. Starting a biologic upon diagnosis will over treat
a significant number of patients. Corticosteroids may be useful in reducing inflammation rapidly and have been shown to
retard erosion, but they should not be used as the only DMARD unless exceptional circumstances prevail.
f. oral corticosteroids
False. DMARD therapy should be started upon diagnosis of rheumatoid arthritis to reduce disease activity and control
joint damage. Early treatment and tight monitoring of disease activity are fundamental to achieve better outcomes. Due
to its efficacy and safety profile methotrexate is nowadays considered the preferred DMARD to be initiated at diagnosis.
Sulphasalazine and other synthetic DMARDs are generally positioned as alternatives to MTX in case of intolerance or
contraindication. There is no prescribed starting regime for DMARD in RA. Most authorities will recommend
methotrexate, or a combination of DMARDs based on methotrexate. Early data are emerging for the introduction of a
biologic agent from the outset in selected patients with particularly bad prognostic markers. However, this patient was
clearly undertreated and will likely benefit from methotrexate treatment. Starting a biologic upon diagnosis will over treat
a significant number of patients. Corticosteroids may be useful in reducing inflammation rapidly and have been shown to
retard erosion, but they should not be used as the only DMARD unless exceptional circumstances prevail.
You decide to start therapy with methotrexate in your outpatient clinic and she fulfils the criteria for prescription. After
your discuss benefits and risks, the patient agrees with the treatment plan.
2. What are the 2 additional examinations that should be performed before administration of methotrexate?
a. Dexa scan (Assessment of bone mass density)
False. A DEXA scan should be arranged on the basis of osteoporosis risk which is unrelated to the use of methotrexate
(MTX).
b. Chest X-ray
True. Pulmonary complications of MTX are well described and a baseline chest X-ray is mandatory in order to evaluate
prior lesions.
c. Tuberculin skin test
False. Tuberculin skin test is not routinely required before MTX administration. It can be debatable, in some countries, if
this should be performed upon rheumatoid arthritis diagnosis in order to have the baseline status of this test.
d. Antinuclear antibodies test
False. Testing for ANAs should be done in the diagnostic workout of a polyarthritis but it is not necessary to repeat it
before MTX prescription.
e. Liver Function Tests

True. Liver enzyme disturbances are a recognized MTX adverse effect. Thus liver function should be evaluated before
starting MTX and liver enzymes monitored thereafter.
One month later the patient returns to your clinic reporting epigastric pain and nausea on the day after taking the weekly
10mg dose of methotrexate, which has been unpleasant but manageable. She still has widespread synovitis, ESR is
now 46, CRP 28 and she is feeling miserable. In particular her knees are swollen and painful.
3. What would be the correct response?
a. Switch MTX to parenteral administration and aspirate both knees and inject corticosteroids
True. Parenteral MTX can decrease gastrointestinal adverse effects that occur with oral administration and can increase
drug effectiveness. Joint injections can give a fast relief of pain and can contribute to a bridging therapeutic effect, while
waiting for MTX effect.
b. Stop MTX and start sulphasalazine
False. MTX was used in a relatively .low dose, during a short period of time. It is still possible that a higher dose through
parenteral route will be effective. Drug survival on MTX and MTX global effectiveness has been shown to be superior to
leflunomide nor sulphasalazine.
c. Stop MTX and start leflunomide
False. MTX was used in a relatively .low dose, during a short period of time. It is still possible that a higher dose through
parenteral route will be effective. Drug survival on MTX and MTX global effectiveness has been shown to be superior to
leflunomide nor sulphasalazine.
d. Add a TNF blocking agent
False. As commented previously the low dose and short period of treatment with MTX do not support the switching of
the treatment regime.
Six months later, now on MTX 20mg per week subcutaneous, the patient has clearly decreased the joint count and ESR
and CRP are lower. However she stills reports poor function and fatigue. Hand and foot X-rays show progression in the
erosions in the previously involved MCP joints, to which is now added erosions in several PIP joints and forefoot joints.
4. What would be the best treatment option for the patient?
a. Add a TNF blocking agent
True. This patient would now meet several national guidelines for starting biologics. The patient has several bad
prognostic markers and shows clear cut progression under optimized MTX treatment.
b. Add sulphasalazine and hydroxychloroquine
False. Add sulphasalazine and hydroxychloroquine might improve the patient but it will hardly stop disease progression.
On top of that many patients have problems with the compliance to this treatment regime.
c. Add leflunomide
False. Add leflunomide or cyclosporine again might improve the patient but it will hardly stop disease progression. In
addition, in both cases, adverse effects limit its utilization overtime.
d. Add cyclosporine
False. Add leflunomide or cyclosporine again might improve the patient but it will hardly stop disease progression. In
addition, in both cases, adverse effects limit its utilization overtime.
e. Switch to leflunomide
False. Switch to leflunomide might improve symptoms in a subset of patients but it is not expected that the effect on
structural disease progression will exceed the one obtained with MTX.
The patient doesnt report any symptoms suggestive of tuberculosis, neither epidemiologic risk factors for this

disease. She had a clear chest X-Ray. However, the tuberculin skin test is positive as is a subsequent Quantiferon* test
5. Which would be the best procedure?
a. Avoid TNF blocking therapy, due to risk of reactivation of latent TB. Instead you would keep on using conventional
DMARDs
False. This patient has likely latent TB. He will have to be reviewed by a TB expert in order to exclude active TB. If the
patient has indication for starting biological therapy latent TB is not a contraindication provided that treatment for latent
TB is adequately done.
b. Immediately start TNF blocking therapy as planned
False. This is clearly a wrong response. If the patient would have latent TB, starting TNF blocking therapy will induce TB
reactivation very soon (symptoms can appear during the first month of therapy). Reactivation of TB in the context of TNF
blocking therapy is more frequently extra pulmonary and symptoms can sometimes be difficult to detect.
c. Treatment with isoniazid 300 mg 4 weeks before starting biologic therapy, to be continued for 9 months overall
True. Most guidelines suggest that after starting latent TB treatment, with isoniazid 300 mg for 4 weeks, the patient can
initiate TNF blocking therapy, provided that he will keep treatment up to 9 months with good compliance. The
management of latent TB should be done by a TB expert. In case of Isoniazid toxicity other regimes can be proposed.
Even after latent TB treatment close monitoring for TB symptoms during biologic therapy should be ensured.
d. Treatment with isoniazid 300 mg 9months before starting biologic therapy
False. Most guidelines suggest that after starting latent TB treatment, with isoniazid 300 mg for 4 weeks, the patient can
initiate TNF blocking therapy, provided that he will keep treatment up to 9 months with good compliance. The
management of latent TB should be done by a TB expert. In case of Isoniazid toxicity other regimes can be proposed.
Even after latent TB treatment close monitoring for TB symptoms during biologic therapy should be ensured.
e. Treatment with isoniazid, rifampicin and pyrazinamide before starting biologic therapy
False. Triple therapy should be reserved for the treatment of active TB. If a patient has active TB full treatment should
be offered before starting biologic therapy. Complete control of the infection should be ensured before starting biologic
therapy.
The patient starts with anti TNF therapy (infliximab) given by infusions. MTX was continued. After the second infusion
(week 2) she felt major improvement in her disease. However, at the 6th infusion she experienced an allergic reaction
after 5 minutes of infusion commencement, consisting of shortness of breath and erythema on the chest and arms. Her
blood pressure falls by 15 mmHg systolic for 10 minutes and recovers without fluid infusion. The drug infusion was
stopped immediately, corticosteroid and antihistamine were administered and the patient recovered rapidly. The patient
had also noticed that the initial extremely positive effect of the drug was apparently decreasing.
6. What would be your preferred medical decision?
a. Increase dose and/or frequency of infliximab administration, preceded by pre-treatment with corticosteroid and
antihistamine.
False. This would only be acceptable if constraints on the availability of other medical options exist. This is sometimes
practiced in the treatment of inflammatory bowel diseases due to the limited number of treatment options available. In
the setting of RA treatment the availability of so many treatment options do not justify the risk of inducing a severe
anaphylactic reaction, the costs of higher doses of infliximab and the suboptimal efficacy that would be probably
associated with this option.
b. Switch to etanercept.
True. This is likely the option preferred by most rheumatologists. The patient responded to a TNF antagonist and
developed immunogenicity, leading to an allergic reaction and less efficacy. It is likely that she will respond adequately
to another TNF antagonist. The patient should be aware that after an immunogenic response the same problem is more
likely to occur with other biologics. Etanercept can be a good option as it is less immunogenic than monoclonal
antibodies.

c. Switch to a biologic with a different mechanism of action.

False. Tocilizumab, rituximab or abatacept would be clearly possible options. The decision between answer 2 or any of
the options mentioned in answer 3 would be influenced by the personal experience of the treating physician, patient
options and relative availability of these treatment options in that specific medical centre
d. Refer to a clinical trial unit for clinical trials evaluating novel targets.
False. The patient still has a very high probability of having her disease controlled by any of the approved biologic
treatments. However, this can always be an option to be discussed with the patient.
You decided to switch to etanercept, in combination with MTX. The patient tolerates this treatment very well. She is in
clinical remission at annual review with a DAS28 below 1.6. One year after, a knee replacement is scheduled.
7. Which one modification of medication is required before surgery?
a. Due to preoperative antibiotics discontinuation of medication is not necessary.
False. preoperative antibiotics are used, but still immune suppression and postoperative infection are a major concern.
b. Etanercept should be stopped at least 2 weeks before surgery and can be restarted after wound healing if no signs of
active infection are present.
True. Most guidelines support stopping etanercept for at least this period of time.
c. Etanercept should be stopped at least 16 weeks before surgery and can be restarted after wound healing if no signs
of active infection are present.
False. There is no evidence supporting the interruption of etanercept for such a long period of time.
d. Stop etanercept before surgery like in option 2 and start oral steroids 0.5 mg/kg/day for keeping RA disease activity
under control.
False. Systemic steroids should be avoided due to delay or impairment of healing process and increase of infection risk.
By stopping etanercept for a relatively short period of time the issue of disease flare is generally avoided.
e. Stop etanercept before surgery like in option 3 and start oral steroids 0.5 mg/kg/day for keeping RA disease activity
under control.
False. Systemic steroids should be avoided due to delay or impairment of healing process and increase of infection risk.
By stopping etanercept for a relatively short period of time the issue of disease flare is generally avoided.
Three months later, while on holiday, she presents to the emergency room with anterior chest pain and a diagnosis of
anterior Myocardial Infarction is made. Her etanercept is stopped. She returns to your clinic for advice.
8. Which of the following actions would you support?
a. TNF blockers are contraindicated in patients in whom an MI has occurred and therefore she should remain on MTX
monotherapy.
False. This contraindication does not exist. On the contrary there is evidence of a reduction of cardiovascular events in
patients treated with TNF antagonists.
b. She should resume etanercept injections immediately.
False. It is advisable to check ventricular function as TNF antagonists are contraindicated in patients with heart failure in
class III/IV. RA is associated with higher a priori risk of vascular disease through traditional and non traditional risk
factors. Secondary cardiac prophylaxis should be carefully reviewed and reinforced and a tight control of inflammation
has to be implemented. It is crucial that the patient stops smoking.
c. Heart failure symptoms should be reviewed and an echocardiogram performed to evaluate ventricular function in
order to reassure that a TNF blocking approach remains adequate.
True. It is advisable to check ventricular function as TNF antagonists are contraindicated in patients with heart failure in
class III/IV. RA is associated with higher a priori risk of vascular disease through traditional and non traditional risk

factors. Secondary cardiac prophylaxis should be carefully reviewed and reinforced and a tight control of inflammation
has to be implemented. It is crucial that the patient stops smoking.
d. She should switch to a biologic with a different mechanism of action.
False. There is no evidence so far that other biologics offer a better cardiovascular safety profile as compared to TNF
antagonists.
Clinical case 2

Warning:
this case of a patient with several co-morbidities is an example of the difficulties, in day to day practice, for choosing
the best treatment with the least toxicity. Obviously, in such settings, there may be a variety of acceptable answers and
the proposed responses reflect the subjective opinion of the authors of the course.
A 60 year old man presents to your clinic with a 6 month history of symmetrical pain, stiffness and swelling in PIP and
MCP joints of hands, knees and ankles, together with bilateral forefoot pain. He has also chronic obstructive pulmonary
disease diagnosed by his family doctor (he is a smoker of 40 cigarettes per day for 35 years), previous renal calculus
disease, hypertension and frequent urinary tract infections. He vaguely recalls a severe childhood illness that required
hospitalisation but has no further details his mother has died from breast cancer and his father from lung cancer,
having always had a 'weak chest'. Systemic enquiry reveals 2kg weight loss in the past 12 months, dyspnoea on walking
50m, together with chronic productive cough (variably discoloured sputum), but is otherwise unremarkable. Examination
detects bilateral synovitis in affected joints, together with bilateral apical, mid zone and basal crackles on pulmonary
auscultation. There is the suspicion of early finger clubbing. No other abnormal features emerge. Initial investigations
include Hb 16 g/dL (9.9 mmol/l), normal total leukocyte count and subsets, platelets 570 * 109/l, normal biochemistry
screening aside from alkaline phosphatase 230 u/l and creatinine 135 mol/l. CRP is 87 mg/l and ESR 78 mm/Hr.
Rheumatoid factor test is positive (280 IU/ml) and he is found to be ACPA positive and ANF is 1/40. Plain X-rays of
hands and feet are reported to be unremarkable. The patient is receiving diclofenac and a thiazide diuretic, and uses a
glucocorticoid inhaler and 2 agonist inhaler regularly.

1. Please choose four further investigations that you would deem wise in such a patient
a. Chest X-ray (CXR)
True. Answer should include chest X-ray (CXR), chest computed tomography (CT) pulmonary function tests (PFT) and
sputum culture for tuberculosis (TB) and other micro-organisms. An infection should be suspected in a COPD-patient
with these symptoms and this is particularly important to be ruled out, as this patient is in need for immunosuppressive
anti-rheumatic drugs. Chest CT is advisable based on these findings, as frequently CXR yields insufficient info. At least
in this phase, symptoms are not suggestive of cardiac failure or lung embolism and ordering a ventilation-perfusion scan
and N-terminal pro-brain natriuretic peptide testing does not seem to be justifiable.
b. Ventilation-perfusion scan
False.
c. Chest Computed tomography (CT)
True. Answer should include chest X-ray (CXR), chest computed tomography (CT) pulmonary function tests (PFT) and
sputum culture for tuberculosis (TB) and other micro-organisms. An infection should be suspected in a COPD-patient
with these symptoms and this is particularly important to be ruled out, as this patient is in need for immunosuppressive
anti-rheumatic drugs. Chest CT is advisable based on these findings, as frequently CXR yields insufficient info. At least
in this phase, symptoms are not suggestive of cardiac failure or lung embolism and ordering a ventilation-perfusion scan
and N-terminal pro-brain natriuretic peptide testing does not seem to be justifiable.
d. Pulmonary function tests (PFT)

True. Answer should include chest X-ray (CXR), chest computed tomography (CT) pulmonary function tests (PFT) and
sputum culture for tuberculosis (TB) and other micro-organisms. An infection should be suspected in a COPD-patient
with these symptoms and this is particularly important to be ruled out, as this patient is in need for immunosuppressive
anti-rheumatic drugs. Chest CT is advisable based on these findings, as frequently CXR yields insufficient info. At least
in this phase, symptoms are not suggestive of cardiac failure or lung embolism and ordering a ventilation-perfusion scan
and N-terminal pro-brain natriuretic peptide testing does not seem to be justifiable.
e. Sputum culture for tuberculosis (TB) and other micro-organisms
True. Answer should include chest X-ray (CXR), chest computed tomography (CT) pulmonary function tests (PFT) and
sputum culture for tuberculosis (TB) and other micro-organisms. An infection should be suspected in a COPD-patient
with these symptoms and this is particularly important to be ruled out, as this patient is in need for immunosuppressive
anti-rheumatic drugs. Chest CT is advisable based on these findings, as frequently CXR yields insufficient info. At least
in this phase, symptoms are not suggestive of cardiac failure or lung embolism and ordering a ventilation-perfusion scan
and N-terminal pro-brain natriuretic peptide testing does not seem to be justifiable.
f. N-terminal pro-brain natriuretic peptide testing
False.
The results of these investigations are essentially reassuring aside from changes in both lung fields on CXR and CT
reported to be compatible with COPD. PFTs reveal reduced FEV1 that is not reversed by bronchodilators. The diagnosis
of RA is made and treatment is to be commenced. His DAS28 is 6.6.
2. Please select the 2 best therapeutic regimens for this patient from the following choices (recognising that
other possibilities may exist).
a. Commence infliximab and methotrexate (MTX) immediately.
False.
b. Commence hydroxychloroquine and observe for 6 months.
False.
c. Commence SLZ and MTX in combination with high dose prednisolone (COBRA regimen).
False.
d. Commence SLZ and add MTX and hydroxychloroquine (O'Dell regimen) pending response after three months.
True. there is no ideal therapeutic regimen for this patient as the issues of co-morbidity will significantly influence the
therapeutic choices that can be made. However, it is important to treat RA as aggressively as possible despite
co-morbidity and the use of DMARDs is still mandatory. Options (f) followed by (d) represent reasonable choices in this
case. The selection of MTX as first DMARD therapy is complicated by coincident pulmonary disease (higher risk of
complications such as MTX pneumonitis or lung infection) but this does not contra-indicate its use. Some physicians
would prefer, in this clinical setting, to start with SLZ, given its better pulmonary toxicity profile, and associate latter on
MTX if an adequate response is not achieved with SLZ monotherapy.. Monotherapy with corticosteroids is not an
adequate treatment regime for any RA patient. First line use of biologics is only to be considered in very few, highly
selected patients. In fact this patient has a high probability of infectious complications and is not a good candidate for
treatment with a TNF inhibitor. The COBRA regimen uses high dose corticosteroid which does not seem to be
appropriate given the identified comorbidities.
e. Commence 15mg prednisolone per day and observe for three months.
False.
f. Commence MTX together with folic acid and ascend MTX dose until low disease activity or remission (maximum
30mg/wk).
True. there is no ideal therapeutic regimen for this patient as the issues of co-morbidity will significantly influence the
therapeutic choices that can be made. However, it is important to treat RA as aggressively as possible despite

co-morbidity and the use of DMARDs is still mandatory. Options (f) followed by (d) represent reasonable choices in this
case. The selection of MTX as first DMARD therapy is complicated by coincident pulmonary disease (higher risk of
complications such as MTX pneumonitis or lung infection) but this does not contra-indicate its use. Some physicians
would prefer, in this clinical setting, to start with SLZ, given its better pulmonary toxicity profile, and associate latter on
MTX if an adequate response is not achieved with SLZ monotherapy.. Monotherapy with corticosteroids is not an
adequate treatment regime for any RA patient. First line use of biologics is only to be considered in very few, highly
selected patients. In fact this patient has a high probability of infectious complications and is not a good candidate for
treatment with a TNF inhibitor. The COBRA regimen uses high dose corticosteroid which does not seem to be
appropriate given the identified comorbidities.
The patient starts MTX and achieves a dose of 15mg per week, limited by nausea and abdominal pain lasting about 48
hours after drug administration that are aggravated by higher doses. He is taking folic acid 10mg per week, two days
after MTX. A reduction of the DAS28 from 6.6 to 5.5 was achieved.
3. 3.What would the next option be? (choose one item)
a. Start infliximab and continue MTX.
False.
b. Add SLZ and observe for 6 months.
False.
c. Start MTX subcutaneously.
True. Subcutaneous administration of MTX can reduce the nausea and abdominal pain and will likely increase efficacy.
This should be tried before advancing to other treatment options.
d. Add 15mg prednisolone per day and observe for three months.
False.
He now tolerates MTX 20mg per week but after a further 3 months his DAS28 remains 5.3. His respiratory symptoms
remain similar and he reports that he has increased the frequency of the 2 agonist inhaler for symptomatic relief.
4. What are the best three options for this patient?
a. Start a TNF blocking agent in combination with MTX
False.
b. Change to SLZ monotherapy
False.
c. Add hydroxychloroquine and SLZ to MTX
True. As previously discussed this patient is not a good candidate for TNF blocking therapy. Sulphasalazine
monotherapy after MTX partial response has been disappointing as exemplified in the BeSt study. From the options
shown, triple therapy (O'Dell regimen) seems the optimal choice in this setting. Leflunomide might increase blood
pressure but with adequate surveillance would be also an adequate option. Despite the possible slight increase in
infection adding 5 mg of prednisolone or equivalent could be also a good option, again with tight surveillance.
d. Change to leflunomide
True. As previously discussed this patient is not a good candidate for TNF blocking therapy. Sulphasalazine
monotherapy after MTX partial response has been disappointing as exemplified in the BeSt study. From the options
shown, triple therapy (O'Dell regimen) seems the optimal choice in this setting. Leflunomide might increase blood
pressure but with adequate surveillance would be also an adequate option. Despite the possible slight increase in
infection adding 5 mg of prednisolone or equivalent could be also a good option, again with tight surveillance.
e. Associate low dose corticosteroid

True. As previously discussed this patient is not a good candidate for TNF blocking therapy. Sulphasalazine
monotherapy after MTX partial response has been disappointing as exemplified in the BeSt study. From the options
shown, triple therapy (O'Dell regimen) seems the optimal choice in this setting. Leflunomide might increase blood
pressure but with adequate surveillance would be also an adequate option. Despite the possible slight increase in
infection adding 5 mg of prednisolone or equivalent could be also a good option, again with tight surveillance.
The patient starts triple therapy. 6 months later he re-attends the clinic and remains unwell. His DAS28 is 5.2. As far as
it is possible to verify the compliance to treatment is good. He reports increasing breathlessness and purulent sputum
production in the past few weeks. CXR is unchanged. Sputum samples are sent for staining and culture and are found to
be positive for mycobacterium tuberculosis. A diagnosis of active tuberculosis is made and treatment started with
appropriate combination antibiotic therapy. Triple therapy is discontinued by the treating pulmonary physicians. His joints
remain troublesome and he asks for further intervention.
5. Which one of the following options represents a reasonable approach?
a. Leflunomide should be commenced.
False.
b. Triple therapy (SLZ, HCQ, MTX) should be recommenced.
False.
c. TNF blockade should be commenced after two months of anti-tuberculous therapy.
False.
d. Gold therapy should be commenced.
True. This is a very difficult clinical scenario. Triple therapy has not been successful in treating this patient and the use
of immunossuppressors and/or TNF blockers in the setting of active TB is certainly not a good option. Gold therapy is an
interesting option in this case.
The patient opts for gold injections on the basis that he is 'taking so many tablets'.
6. How do you recommend he receive his gold injections? (1 answer)
a. IV myocrisin or aurothiomalate (50mg) given weekly for twenty weeks then monthly
False.
b. IM myocrisin or aurothiomalate (10mg) test dose then continued as weekly IM injections increasing the dose by 10mg
per week to a target dose of 50mg / wk
False.
c. IM myocrisin or aurothiomalate test dose of 10mg followed by weekly injections of 50mg up to a clinical response and
then reduce to a monthly frequency thereafter
True.
The patient has a dramatic response to gold injections and his DAS28 falls to 2.9 within 3 months and remains well
controlled for the next 18 months.
He returns to your clinic for a routine review and although he is happy you note that his DAS28 has risen to 4.7. He has
completed his TB therapy. Despite intra-articular injection in four involved joints over a two week period his DAS28 three
months later has risen further to 6.4 he requests to discontinue gold injections.
7. How should you now manage his active RA? (3 right answers)
a. Start etanercept together with low dose methotrexate
True. the clinical scenario continues to be very difficult. Thus, again despite their potential infectious risk, use of
biologics must be considered. It would be wise to vaccinate with seasonal and pandemic flu vaccinations and with
Pneumococcal vaccination prior to commencing any biologic therapy. TB has now been cured. Therefore, using an

anti-TNF is not formally contra-indicated. The risk of TB is lower with etanercept than with monoclonal antibodies. Thus,
etanercept (associated with methotrexate because of better efficacy) could be an option. Abatacept and tocilizumab
seem also to be associated with a lower risk of TB infection as compared to anti TNF monoclonal antibodies. Rituximab
is associated with increased infectious risk but not specifically with increased TB risk.
b. Start etanercept used as monotherapy
False. the clinical scenario continues to be very difficult. Thus, again despite their potential infectious risk, use of
biologics must be considered. It would be wise to vaccinate with seasonal and pandemic flu vaccinations and with
Pneumococcal vaccination prior to commencing any biologic therapy. TB has now been cured. Therefore, using an
anti-TNF is not formally contra-indicated. The risk of TB is lower with etanercept than with monoclonal antibodies. Thus,
etanercept (associated with methotrexate because of better efficacy) could be an option. Abatacept and tocilizumab
seem also to be associated with a lower risk of TB infection as compared to anti TNF monoclonal antibodies. Rituximab
is associated with increased infectious risk but not specifically with increased TB risk.
c. Retrial of low dose methotrexate
False. Low dose MTX is unattractive on the basis of previous inefficacy.
d. Start leflunomide
True. Leflunomide could be a reasonable option although careful control of blood pressure would be required.
e. Start rituximab with low dose methotrexate
True. the clinical scenario continues to be very difficult. Thus, again despite their potential infectious risk, use of
biologics must be considered. It would be wise to vaccinate with seasonal and pandemic flu vaccinations and with
Pneumococcal vaccination prior to commencing any biologic therapy. TB has now been cured. Therefore, using an
anti-TNF is not formally contra-indicated. The risk of TB is lower with etanercept than with monoclonal antibodies. Thus,
etanercept (associated with methotrexate because of better efficacy) could be an option. Abatacept and tocilizumab
seem also to be associated with a lower risk of TB infection as compared to anti TNF monoclonal antibodies. Rituximab
is associated with increased infectious risk but not specifically with increased TB risk.
f. Start abatacept accompanied by low dose methotrexate
False. the clinical scenario continues to be very difficult. Thus, again despite their potential infectious risk, use of
biologics must be considered. It would be wise to vaccinate with seasonal and pandemic flu vaccinations and with
Pneumococcal vaccination prior to commencing any biologic therapy. TB has now been cured. Therefore, using an
anti-TNF is not formally contra-indicated. The risk of TB is lower with etanercept than with monoclonal antibodies. Thus,
etanercept (associated with methotrexate because of better efficacy) could be an option. Abatacept and tocilizumab
seem also to be associated with a lower risk of TB infection as compared to anti TNF monoclonal antibodies. Rituximab
is associated with increased infectious risk but not specifically with increased TB risk.
g. Start tocilizumab
False. the clinical scenario continues to be very difficult. Thus, again despite their potential infectious risk, use of
biologics must be considered. It would be wise to vaccinate with seasonal and pandemic flu vaccinations and with
Pneumococcal vaccination prior to commencing any biologic therapy. TB has now been cured. Therefore, using an
anti-TNF is not formally contra-indicated. The risk of TB is lower with etanercept than with monoclonal antibodies. Thus,
etanercept (associated with methotrexate because of better efficacy) could be an option. Abatacept and tocilizumab
seem also to be associated with a lower risk of TB infection as compared to anti TNF monoclonal antibodies. Rituximab
is associated with increased infectious risk but not specifically with increased TB risk.
Conclusion : After careful discussion with the patient and the family, during 2 consecutive appointments, rituximab plus
low-dose methotrexate was started.
6 months later the patient is much better with no deterioration of his pulmonary symptoms.