John Tesser, MD, FACP, FACR, prepared useful Practice Aids pertaining to rheumatoid arthritis for this CME activity titled "Overcoming Challenges in the Management of Refractory Rheumatoid Arthritis: Expert Insight on the Clinical Potential of Novel Therapeutic Options." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2GoDoEt. CME credit will be available until April 28, 2020.

1. Access the activity, “Overcoming Challenges in the Management of Refractory
Rheumatoid Arthritis: Expert Insight on the Clinical Potential of Novel Therapeutic
Options,” at PeerView.com/XQR40.
Optimizing the Use of
Methotrexate in the Treatment
of Rheumatoid Arthritis
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
MTX: methotrexate; RA: rheumatoid arthritis.
1. Bello AE et al. Open Access Rheumatol. 2017;9:67-79. 2. Hoekstra M et al. et al. J Rheumatol. 2006;33:481-485.
MTX remains the cornerstone
therapy for patients with RA,
with well-established safety
and efficacy profiles and support in
international guidelines1
Though clinical and radiologic
results indicate benefits of MTX
monotherapy and combination
therapy, patients may not receive
optimal dosing, duration, or route of
administration to maximize their response1
The bioavailability of oral, higher-dose MTX in adult patients with
RA can be improved by splitting the dose2
Summary Recommendations for MTX Optimization1
Administration of a high initial dose of MTX followed by rapid titration can improve the
response to oral MTX and does not appear to compromise safety or tolerability1
Treatment with oral MTX, with appropriate dose titration, should be continued for at least
6 months to accurately assess clinical response (if the patient has experienced any response
to treatment by 3 months)2
Patients for whom MTX treatment fails because of intolerability or inadequate efficacy
may be “rescued” by switching to subcutaneous MTX3
Consideration should also be given to starting with subcutaneous MTX given its favorable
bioavailability and pharmacodynamic profile4
Starting patients on subcutaneous MTX or switching from oral to subcutaneous delivery
is likely to improve treatment persistence5
If a patient is switched from oral to subcutaneous MTX, a concomitant dosage increase
should be avoided. After change in delivery route, the dose may be titrated as needed6
If a patient has tolerated MTX monotherapy but not responded adequately, another agent
may also be prescribed. In such cases, MTX dosage and route of administration used before
treatment augmentation should be maintained, with titration as needed7

2. Access the activity, “Overcoming Challenges in the Management of Refractory
Rheumatoid Arthritis: Expert Insight on the Clinical Potential of Novel Therapeutic
Options,” at PeerView.com/XQR40.
A Closer Look at Biologic and
Small Molecule Targets in
Rheumatoid Arthritis1
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
APC: antigen-presenting cell; BCR: B-cell receptor; CD: cluster of differentiation; GM-CSF: granulocyte-macrophage colony-stimulating factor; IL: interleukin; JAK: Janus kinase; MHC: major
histocompatibility complex; RANK: receptor activator of nuclear factor κB; RANKL: receptor activator of nuclear factor κB ligand; TCR: T-cell receptor; Tfh
: T follicular helper; Th
: T helper.
1. Smolen JS et al. Nat Rev Dis Primers. 2018;4:18001.
PRACTICE AID
IL-12
IL-23
MHC
TCR
T cell
CD28
CD80
CD86 IFNγ IL-2
IL-21
Co-stimulation
CD40L CD40
CD20
BCR
B cell
Anti-CD20 drugs
Rituximab
CD80 and CD86 inhibitors
Abatacept
RANK?
Complement
receptor
Macrophage
IFNγ
IL-17
RANKL
Fc
receptor
Immune
complexes
IL-15
IL-18
Th
1/
Th
17/
Tfh
IL-6
GM-CSF
Plasma cell
Autoantibody
RANKL
Fibroblast
Chondrocyte
IL-6R
Osteoclast
TNF
IL-1
IL-6
JAK
inhibitors
Baricitinib and
tofacitinib
TNF inhibitors
Adalimumab, certolizumab,
etanercept, golimumab, and infliximab
IL-6R inhibitors
Tocilizumab and sarilumab
APC
JAK
signalling

3. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Disease-Modifying Antirheumatic
Drugs for Rheumatoid Arthritis
CD: cluster of differentiation; DMARD: disease-modifying antirheumatic drug; IL: interleukin; JAK: Janus kinase; RA: rheumatoid arthritis
1. Smolen JS et al. Nat Rev Dis Primers. 2018;4:18001. 2. Olumiant (baricitinib) Prescribing Information. http://pi.lilly.com/us/olumiant-uspi.pdf. Accessed April 5, 2019. 3. Kevzara (sarilumab) Prescribing Information. http://products.sanofi.us/kevzara/kevzara.pdf.
Accessed April 5, 2019.
PRACTICE AID
Access the activity, “Overcoming Challenges in the Management of Refractory Rheumatoid Arthritis: Expert Insight
on the Clinical Potential of Novel Therapeutic Options,” at PeerView.com/XQR40.
Currently Available DMARDs for RA1
An Overview of the Newest Treatment Options for RA
Synthetic DMARDs
Conventional synthetic DMARDs
• Unknown target: Methotrexate, sulfasalazine, chloroquine, and
hydroxychloroquine
• Known target: Dihydroororate dehydrogenase for leflunomide
Targeted synthetic DMARDs
• JAK1 and JAK 2: Baricitinib
• JAK1, JAK2, and JAK3: Tofacitinib
Biological DMARDs
Targets of biologic originator DMARDs
• Tumor necrosis factor: Adalimumab, certolizumab, etanercept, golimumab, and
infliximab
• IL-6 receptor: Tocilizumab and sarilumab
• CD80 and CD86 (involved in T-cell costimulation): Abatacept
• CD20 (expressed by B cells): Rituximab
Targets of biosimilar DMARDs
• Tumor necrosis factor: Adalimumab, etanercept, and infliximab
Drug FDA Approval Mechanism of Action Indication Route of Administration Adverse Reactions
Baricitinib2
May 2018 JAK inhibitor
Adult patients with moderately to
severely active RA who have had an
inadequate response to one or more
TNF antagonist therapies
Oral
Upper respiratory tract infections,
nausea, herpes simplex, and
herpes zoster
Sarilumab3
May 2017 IL-6 receptor antagonist
Adult patients with moderately to
severely active RA who have had an
inadequate response or intolerance to
one or more DMARDs
Subcutaneous
Neutropenia, increased ALT,
injection-site erythema, upper
respiratory infections, and urinary
tract infections