William F. C. Rigby, MD, and Gregg J. Silverman, MD, prepared useful Practice Aids pertaining to rheumatoid arthritis for this CME activity titled "Improving Outcomes for Patients With Refractory Rheumatoid Arthritis: The Role of JAK Inhibitors." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2MLFVtI. CME credit will be available until October 8, 2019.

1. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
A Closer Look at the Role of JAK
Inhibitors for the Treatment of
Rheumatoid Arthritis
PRACTICE AID
Access the activity, “Improving Outcomes for Patients With Refractory Rheumatoid Arthritis:
The Role of JAK Inhibitors,” at www.peerview.com/MJP40.
JAK2/TYK2 JAK2/JAK2JAK1/JAK2JAK1/JAK2/TYK2JAK1/TYK2JAK1/JAK3• Growth/maturation of
lymphoid cells
• Differentiation/
homeostasis of T cells,
NK cells
• B-cell class switching
• Inflammation
• Antiviral
• Inflammation
• Antitumor
• Naïve T-cell
differentiation
• T-cell homeostasis
• Inflammation
• Antiviral
• Inflammation
• Innate immunity
• Differentiation/
proliferation of Th17 cells
• Inflammation
• Erythropoiesis
• Myelopoiesis
• Megakaryocyte/platelet
production
• Growth
• Mammary development
Function
JAK1 JAK1 JAK1 JAK1 JAK2 JAK2 TYK2 JAK2 JAK2
TYK2
JAK2TYK2JAK3
The Complex Pathophysiology of RA1
JAK-Dependent Cytokines Involved in the Pathogenesis of RA Include
IL-1RA, IL-1α, IL-1β, IL-11, IL-13, IL-17, IL-18, TGFβ, and TNF2-6
Adaptive response
Plasmacytoid DC
TLR
Costimulatory
receptor
IFNα, IFNβ,
IL-15, IL-18
Regulatory T cell
IL-10,
TGFβ
IL-23, IL-6,
TGFβ, IL-12,
IL-15, IL-18
TH0 TH17
(or TH1)
APRIL,
BAFF
IL-6,
IL-10
Germinal-center
formation
(LTβ, CXCL13, CCL21)
B cell Plasma cell
Myeloid DC
Autoantibody
synthesis
Cartilage matrix damage
Innate response
Synovial hyperplasia
Osteoblast
Chondrocyte
Synovial fibroblast
PAR2 Macrophage
VEGF, bFGF
Endothelial
cell
Angiogenesis
Adipocyte
FcγR
Mast cell Neutrophil
Inflammation
Atherogenesis and
metabolic syndrome
IL-17, RANKL,
cell contact
IL-15, TNF, IL-6,
IL-18, cell contact
IL-1, TNF,
RANKL,
M-CSF, IL-17
IL-1, IL-18,
TNF, M-CSF,
IL-17
IL-1, TNF, IL-6,
TGFβ, IL-17,
IL-32
Adiponectin,
TNF, IL-6, IL-15,
IL-1, resistin

2. A Closer Look at the Role of JAK
Inhibitors for the Treatment of
Rheumatoid Arthritis
APRIL: A proliferation-inducing ligand; BAFF: B-cell activating factor; bFGF: basic fibroblast growth factor; CCL21: C-C motif chemokine ligand 2; CXCL: CXC chemokine ligand; DC: dendritic cells; csDMARDs: conventional synthetic disease-modifying antirheumatic
drugs; DMARDs: disease-modifying antirheumatic drugs; FCyR: Fc-gamma receptor; IFN: interferon; IL: interleukin; IL-1RA: interleukin 1 receptor antagonist; IR: incidence rates; JAK: Janus kinase; LTβ: lymphotoxin-beta; M-CSF: macrophage colony-stimulating factor;
MTX: methotrexate; NK: natural killer (cells); PAR2: proteinase-activated receptor-2; RANKL: receptor activator of nuclear factor-ΚB ligand; STAT: signal transducers and activators of transcription; TGFβ: transforming growth factor beta; Th17: T helper 17 (cells); TLR: toll-
like receptors; TNF: tumor necrosis factor; URTI: upper respiratory tract infection; VEGF: vascular endothelial growth factor.
1. McInnes IB, Schett G. Nat Rev Immunol. 2007;7:429-442. 2. Ghoreschi K et al. J Immunol. 2011;186:4234-4243. 3. Kontzias A et al. Curr Opin Pharmacol. 2012;12:464-470. 4. McInnes IB, Schett G. N Engl J Med. 2011;365:2205-229. 5. O’Sullivan LA et al. Mol Immunol.
2007;44:2497-2506. 6. Vijayakrishnan L et al. Trends Pharmacol Sci. 2011;32:25-34. 7. Louder A et al. Am Health Drug Benefits. 2016;9:84-93. 8. Alten R et al. Patient Prefer Adherence. 2016;10:2217-2228. 9. https://www.accessdata.fda.gov/drugsatfda_docs/
label/2016/208246s000lbl.pdf. Accessed September 6, 2018. 10. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207924s000lbl.pdf. Accessed September 6, 2018. 11. https://clinicaltrials.gov. Accessed September 6, 2018.
PRACTICE AID
Access the activity, “Improving Outcomes for Patients With Refractory Rheumatoid Arthritis:
The Role of JAK Inhibitors,” at www.peerview.com/MJP40.
• Treatment with biologic agents results in disease suppression for many patients with RA, but only ~30% achieve complete
remission; and the majority of patients treated with biologics experience disease exacerbation following cessation of treatment
• The route of administration is also an important consideration, with some studies suggesting that patients may prefer oral
therapies over those with other routes of administration
• Given the important role played by JAK-STAT signaling in the development of RA and other autoimmune conditions,
small-molecule JAK inhibitors have been proposed as an important treatment option
JAK Inhibitors Currently in Phase 3
Development for the Treatment of RA11
Filgotinib
(FINCH program)
Peficitinib
(RAJ program)
Upadacitinib
(SELECT program)
Why Is There a Need
for JAK Inhibitors
in the RA Treatment
Landscape?7,8
Approved JAK Inhibitors for the Treatment of RA
Overview
Efficacy in Specific
Clinical Scenarios
Monotherapy + csDMARDs MTX-IR
After
anti-TNF
failure
Tofacitinib9
• Approval date: November 2012
• JAK selectivity: JAK1 and JAK3
• Indication: Treatment of adult patients with moderately to severely active RA
who have had an inadequate response or intolerance to MTX; may be used as
monotherapy or in combination with MTX or other nonbiologic DMARDs
• Most common side effects: URTI, nasopharyngitis, diarrhea, and headache
Barcitinib10
• Approval date: May 2018
• JAK selectivity: JAK1 and JAK2
• Indication: Treatment of adult patients with moderately to severely active RA
who have had an inadequate response to one or more TNF-antagonist therapies
• Most common side effects: URTI, nausea, cold sores, and shingles

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.
The Impact of Rheumatoid Arthritis
on Patients1
RA: rheumatoid arthritis.
1. https://rheumatoidarthritis.net/infographic/ra-not-just-joints-or-bones-but-so-much-more/. Accessed August 31, 2018.
PRACTICE AID
Access the activity, “Improving Outcomes for Patients With Refractory Rheumatoid Arthritis: The Role of
JAK Inhibitors,” at www.peerview.com/MJP40.
Apart from joint pain, there are many more
symptoms patients may experience
73% of patients
wish they had
known more
about all RA
symptoms when
they were first
diagnosed
Also affected:
heart, skin,
kidneys, and
lungs
RA impacts various body parts,
joint pain being a key symptom
At diagnosis, 66% of patients reported wishing they knew more about the impact RA can have on mental health
Hands and wrists 95%
Fingers 88%
Feet 84%
Legs and knees 78%
Shoulders 70%
Ankles 66%
Hips 66%
Arms and elbows 65%
Neck 55%
Back 52%
Eyes 45%
Head and jaw 40%
Chest 21%
19% initially experienced
anxiety and/or depression
53% actively experience
anxiety and/or depression
25% actively experience
mood disorder
Patients report that rheumatoid arthritis negatively impacts:
Exercise
70%
Household/family
duties 64%
Sleep
61%
Work
61%
Social life/participating
in activities 59%
Osteoarthritis
and obesity
are the most
common of
other health
conditions
95% of patients suffer
from other health conditions
Chronic pain 41%
Hypertension 37%
Neuropathy 34%
Fibromyalgia 31%
Dental issues 31%
Sleep disorders 23%
Sjörgren’s syndrome 17%
Heart disease 7%
Fatigue 89%
Reduced grip
strength 70%
Difficulty
sleeping 67%
Cognitive
impairment 54%
Visual symptoms
51%
Numbness/
tingling 47%
Dry mouth 42%