The New Yorker Joint Venture:
New Concepts and New Treatment for
Inflammatory Arthritis
Richard S Pope MPAS, PA-­‐C, DFAAPA, CPAAPA Western CT Medical Group Dept. of Rheumatology Danbury, CT That’s a trash fire Trump’s inaugura1on is over there>>>> What is Ankylosing
Spondylitis
The word is from Greek ankylos meaning s2ffening, spondylos meaning vertebra, and -­‐i,s meaning inflamma2on.[2] The cause of ankylosing spondylitis is unknown
however, it is believed to involve a combination of genetic and environmental factors.
The underlying mechanism is believed to be autoimmune or autoinflammatory.
Diagnosis is typically based on the symptoms with support from medical imaging and blood tests.
AS is a type of seronegative spondyloarthropathy,
meaning that tests show no presence of rheumatoid factor (RF) antibodies AS is one of the Spondyloarthri3des (SpA)
What is Spondyloarthritis?
is an umbrella term for inflammatory diseases that involve both the joints and
entheses--the sites where the ligaments and tendons attach to the bones
The most common of these diseases is Ankylosing Spondylitis
And includes many others
Famous people with Ankylosing Spondyli3s
PsoriaCc arthriCs •  Dan Reynolds lead singer with Imagine Dragons. Non radiographic axial SpA Enteropathic arthriCs SpondyloarthriCs Ankylosing spondyliCs ReacCve arthriCs UndifferenCated SpA Khan MA, Ankylosing Spondyli,s. 2009;1-­‐47 Van der Linde S et al. Kelley’s Textbook of Rheumatology. 8th ed. 2008; 1169-­‐1189 Zochling J et al. Rheumatology (Oxford). 2005; 44(12): 1483-­‐1491 •  His story “started in my hips. I couldn’t move and felt drilling in my nerves” •  Scariest moments when he “could not get out bed” •  When he was first diagnosed he was newly married and then had a baby. •  Misdiagnosed by “lots of Doctors” •  Finally saw rheumatologist and “got on medicine and now I am in remission” •  He is now 29 and came forward with his disease •  “The disease has taught me a lot about life and ‘gave me compassion’, taught me discipline”. •  It has given me “more passion for life” •  Now is a spokesperson for AS and thisaslife.com Spondyloarthri3s-­‐ More common than RA?
Learning objec3ves
1.  Discuss new concepts of the natural history of the AxSpA 2.  Differen2ate between old and new criteria for diagnosis of axial SpA 3.  Explain the role of conven2onal radiography and MR imaging, lab tes2ng and gene2c markers 4.  Adopt management strategies using older and newer pharmaceu2cal agents “Axial spondyloarthri2s may be as prevalent as rheumatoid arthri2s” •  2009-­‐2010 NHANES • 
• 
• 
• 
• 
6,684 screened ages 20-­‐69 5,106 interviewed 20% of Americans have low back pain 6% have inflammatory low back pain axSpA 0.9-­‐1.4% prevalence Rheumatoid prevalence 0.6%-­‐1%! axSpA 0.9-­‐1.4% Could it be that we are underdiagnosing? Come in to my office. You’ll see a lot more of this
than this. Why? Courtesy of Assessment of Spondyloarthri2s Interna2onal Society There Are More Than 100 Forms of Arthritis
Epidemiology of Rheumatic Diseases
• 
• 
• 
• 
• 
1 in 8 persons has osteoporosis
1 in 10 persons has osteoarthritis
1 in 33 persons has fibromyalgia
1 in 100 persons has RA
1 in 350 persons has PsA
+ IBD arthritis
+ Undiff. Sacroiliitis
1 in 1000 persons has ankylosing spondylitis
+ ReA Reactive arthritis
= 1.3-­‐1.4 million in USA •  1 in 2000 persons has systemic lupus erythematosus
•  1 in 10,000 persons has scleroderma
New concept of AS and Related Spondyloarthri3s (SpA)
Predominately Axial Disease Predominately Peripheral Disease Ankylosing spondyli2s (radiograph SpA) Nonradiographic Axial SpA (nr-­‐AxSpA) Reac2ve arthri2s ReA Psoria2c arthtri2s PsA Inflammatory bowel disease-­‐
associated arthri2s Undifferen2ated SpA Index of Background terms
•  SpA •  ax-­‐SpA •  nr-­‐SpA (undifferen2ated SpA) •  ASAS •  PsA •  ReA-­‐(Reiter’s) •  AS •  Spondyloarthri2s •  Axial spondyloarthri2s •  Non-­‐radiographic axial spondyloarthri2s •  Assessment of Spondyloarthri2s Interna2onal Society •  Psoria2c Arthri2s •  Reac2ve Arthri2s •  Ankylosing Spondylii2s Case study
•  39 year old Caucasian male referred for LBP •  CC: Acute onset of Low back and bilateral bumock pain aner skiing 5 weeks previously. •  HPI: In addi2on to low back and bumock pain he complains of neck soreness and then the discomfort went to his mid back between his shoulder blades and then his hips. It became difficult to breathe and had anterior chest pain. •  PMHx: History of Crohn’s disease, anemia, hypertension, CKD stage III with nega2ve renal biopsy, except scarring likely due to hypertension. Case Study
•  Labs: •  ESR-­‐85 mm/hr •  CRP-­‐46.0 mg/L ULN 10 •  BMP-­‐CREAT 1.89 mg/Dl •  BUN-­‐31 mg/Dl •  HLA B-­‐27 nega2ve •  RF-­‐nega2ve •  ANA-­‐nega2ve •  CBC-­‐ Hgb 11.7 Hct 31.2 Pelvis with bilateral hips
What is the X-­‐ray finding? Case History Radiology
•  Radiology-­‐x-­‐ray bilateral hip and SIJ: •  Significant sclerosis and irregularity of the SIJ consistent with osteoarthri2s but no evidence of hip disease. •  Impression: sclerosis and irregularity of bilateral SIJs consistent with sacroilii2s •  X-­‐ray thoracic spine: Impression •  There is mild curvature of the thoracic spine with convexity to the len in the lower thoracic spine. This curvature was not present in 10/27/2008. Epidemiology of AS
•  AS is 2 to 3 2mes more common in males than in females •  Symptoms usually start between 20 and 30 years of age •  Most pa2ents with AS are either diagnosed late or already compromised upon diagnosis •  The mean delay in the diagnosis of AS ranges between 5 to 11 years Etiology of AS
Modified New York Criteria for AS 1984
Clinical criteria:
•  Precise etiology unclear
•  Strong genetic predisposition highlighted by familial occurrence and HLAB27
•  ~ 50% of the risk of developing AS is from HLA-B27
•  However HLA B-27 is not necessary or sufficient to cause the disease
1.  Low back pain and stiffness for more than 3 months that improves with
exercise, but is not relieved by rest
2. Limitation of motion of the lumbar spine in both the sagittal and frontal
planes
3. Limitation of chest expansion relative to normal values correlated for age
and sex
Radiological criteria:
Sacroiliitis grade ≥ 2 bilaterally or grade 3-4 unilaterally
•  Twin studies show susceptibility of 90%
Definite AS:
•  Recurrence risk ratios of developing AS in a 1° relative is ~8%
If the radiological criterion is associated with
at least 1 clinical criterion
van der Linden S., Arthritis Rheum. 1984;27:361-368
ASAS classifica*on for Axial spondyloarthri*s SpA
Diagnosis of AS
In patients with > 3mths of back pain and age at onset <45 yoa
SacroiliiCs on imaging plus > OR
1 SpA feature HLA-­‐B27 + plus >2 other SpA features SPA features SacroiliiCs on imaging • 
• 
• 
• 
• 
• 
• 
• 
• 
Inflammatory back pain ArthriCs EnthesiCs (heel) UveiCs DactyliCs Psoriasis Crohn’s disease/coliCs FHx of SpA Elevated CRP •  AcCve inflammaCon on MRI •  Definite x-­‐ray sacroiliiCs according to modified NY criteria SensiCvity 82.9% Specificity 84.4% •  Establishing the diagnosis is onen difficult •  The presen2ng manifesta2ons can be wide ranging •  Thus, a variety of health care professionals may see these pa2ents •  Primary care providers •  Ophthalmologists •  Podiatrists •  Other medical and surgical specialists (pain prac2ces, orthopods) •  Rheumatologists Rundelwait 2009 Primary Care and Rheumatology
Improves patient outcomes
Primary care
Collaboration
Rheumatologist
•  Suspected diagnosis •  Confirm diagnosis •  Early referral to rheumatologist •  Ini2ate early, aggressive DMARD therapy •  Monitor for disease progression, medica2on toxici2es, and comorbidi2es including OP and CVD •  Ins2tute vaccina2ons before immunomodulatory therapy •  Monitor for disease progression, medica2on toxici2es, and comorbidi2es including OP and CVD Inflammatory Back Pain
Definition
•  It is important to dis2nguish between mechanical low back pain and Inflammatory back pain. •  Dura2on > 30 minutes •  No improvement with rest •  Awakening from pain in the second half of the night •  Alterna2ng bumock pain sensitivity of 70.3% and a specificity of 81.2% Rudalwait, M. et al, Jan. 30, 2006 Arthri2s and Rheuma2sm Approach to diagnosis of axial
spondyloarthropathy
Clinical Conceptualiza3on of the Natural History of axSpA: An Emerging Model
Chronic low back pain (5%probability of axial SpA) Subclinical process in gene2cally predisposed pa2ents a
Inflammatory back pain Yes (14% probability) No (2% probability) b Inflammatory back pain d Spontaneous remission HLA-­‐B27 c Non-­‐radiographic axSpA Yes (59%) No (<2%) Rheumatologist: Evalua2on of clinical SpA (enthesi2s, uvei2s, bumock pain, Peripheral arthri2s, dactyli2s, Psoriasis, Crohn’s, + NSAID reponse -­‐Acute phase reactants -­‐HLA-­‐B27 -­‐Imaging (x-­‐ray MRI) Quiescent disease ac2vity e
No further tes2ng Unless SpA strongly suspected Judgement on probability of axial SpA UpToDate ᴿ2014 decision tree for primary care axSpA Other features
g
Non-­‐radiographic axSpA Ankylosing f spondyli2s (AS) Non-­‐progressing AS i h AS late complica2ons Garg N. Bosch F. Deodhar A. Best Pract Res Clin Rheumatol. 2014 Oct;28(5):663-­‐672. Asymmetric oligoarthri3s
• Asymmetric oligoarthri2s • Psoriasis • Uvei2s • Enthesi2s No radiographic evidence at early stages Acute uveitis
Enthesi3s Hallmark of AS •  Enthesis=amachment of tendon, ligament or joint capsule. Enthesis is a complex structure that appears to be a principal site of inflamma2on of SpA •  Enthesi2s can be an early and prominent feature of SpA Direct and consensual photophobia to light in led eye 25-­‐40% develop this sign •  Inflamma2on in AxSpA primarily affects the sacroiliac joints and axial skeleton •  Bony tenderness occurs from enthesi2s at many other sites-­‐costosternal, spinous process, greater trochanter, iliac crests, and ischial tuberosity, 2bial tubercles or heels.¹´² 1. Khan MA. Spondylarthropathies. Atlas of Rheumatology, 2002
2. Khan MA, Ann Intern Med 2002.
Inflammatory
Enthesitis
Sacroilii3s on Pelvis film Stage III
Irregular borders Fluffy boney appearance Narrowing Case study of pt. with 2 years of symptoms What is the role of MRI in AS?
Sacroiliitis by MRI
Thick Arrows:
Normal SI joint x-­‐ray Pt had sxs of Inflammatory back pain for 2 yr • Chronic low back for > 3 months • Started before the age of 45 Subchondral marrow
inflammation
shown by
increased MRI
signal
•  5% chance of having SpA So in this age of cost control and concern regarding ordering expensive tests what do you do? Thin Arrow:
Joint cavity
Then H and P should include
•  Does the pa2ent have a family history or past history of AS/SpA? •  Does the pa2ent have inflammatory back pain? -­‐ increases odds to 14% •  Does the pa2ent have difficulty touching his/her toes? •  Are they tender over one or both SIJs? •  Do they have a + Schober test? In this situa2on if either HLA-­‐B27 is + or abnormal x-­‐ray or MRI then Odds are increased Pros and cons MRI in spondyli3s
• Pros •  Detect bone marrow edema STIR •  Synovi2s •  Erosions •  Fat deposi2on •  Ankylosis • LimitaCons •  Bone marrow edema •  BME can be seen in normal •  Absence of BME does not rule out •  BME seen in trauma and with O/A Pathology of AS Schema3c sequence of events in AS vs RA
AS is characterized by 2 key pathological findings: inflamma3on at the enthesis and new bone forma3on in the sacroiliac joint and in the spine
AS sequence of events Tendon/ligament Enthesis (fibrocar2lage) Bone Enthesi2s/Ostei2s Bone resorp2on Bone remodeling New bone forma2on and ankylosis AS RA Inflamma2on fluctua2ng Inflamma2on replacement by repair 2ssue Erosive Bone Destruc2on Inflamma2on Erosive Bone persis2ng Destruc2on Osteoprolifera2on syndesmophytes AS Structural damage score RA Structural damage score Time 1. 
RA response vs Spondyloarthri3s Rheumatoid is catabolic Gene3c Marker HLA-­‐B27
•  AS Caucasians 90% + for HLA-­‐B27 Mechanism of acCon Four major hypothesis¹ •  Car2lage loss •  Erosions 1.  MHC class I an2gen presenta2on in HLA-­‐B27+ pts 2.  Spondyloarthri2s catabolic plus anabolic •  Anabolic causes syndesmophyte forma2on •  And ankylosis of joints •  Molecule misfolds •  Result-­‐more easily recognized by natural killer cells 2. HLA-­‐B27 can modulate the human microbiome •  cross reacts with certain gram nega2ve bacteria •  as seen with reac2ve arthri2s •  high prevalence of subclinical intes2nal inflamma2on in AS pa2ents 1. Davis JC Jr, et al. Athri,s Rheum. 2007;57:1050-­‐1057. 2. Furst DE, et al. Rheumatology. 2013;52: 1845-­‐1855. 3. Deodhar A, et al. Arthri,s Care and Res.2010;62: 1266-­‐1271. 4. Visvanathan S. et al. Ann Rheum Dis. 2009;68(2):175-­‐182. 5. Dougados M, et al. Ann Rheum Dis. 2011;70(5): 799-­‐804 1. The Rheumatologits vol. 10 July 2016 pages 16-­‐17 Genetic Susceptibility
in
PSO PSA
LCE
Gene
Cluster
HLACw0602
IL-12
IL-23
IL-13 SLC22A4
Gene Cluster
Treatment op3ons
•  Physical therapy •  Extension exercises, weight maintenance/reduc2on •  Smoking cessa2on-­‐restric2ve disease due to chest wall involvement •  NSAIDs important role •  Majority 50% or > response •  DMARDs limited role Psoriasis
Psoriatic
Arthritis
Published on Nov 27, 2012
A lecture for trust members and the public by Dr Arvind Kaul consultant in rheumatology / acute medicine,
Royal Free London NHS Foundation Trust, Thursday 11 October 2012
•  Sulfasalazine-­‐may be useful in peripheral arthri2s •  Methotrexate-­‐no efficacy •  Leflunomide-­‐no efficacy Treatment op3ons
Treatment op3ons
•  TNF inhibitors: •  improve quality of life •  Etanercept •  Infliximab •  Adalimumab •  Golimumab •  Certolizumab •  anemia •  sleep quality •  fa2gue •  bone density •  forced vital capacity¹−⁵ Newer treatment op3ons for AS Pathogenesis of RA
B-cell inhibitor
Rituximab
Antibodies
B
B cell
cell
Immune complexes
Newer treatment op3ons for PSO
2010 ASAS/EULAR Recommenda3on for Management of AS
•  Non-­‐pharmacologic therapy TT cell
cell
IFN-γ and
-DR
other
cytokines
Macrophage
Macrophage
B cell or macrophage
TNF-α
IL-1
IL-6
IL-17a
Synoviocytes
Pannus
TOC
Articular
cartilage
1. Song IH, et al. Ann Rheum Dis. 2011 Jun;70(6):1108-­‐1110. 2. Song IH, et al. Arthri,s Rheum. 2010;62: 1290-­‐1297. 3. Kiltz U, et al. Curr Opin Rheumatol . 2012;24:252-­‐260 •  Ixekizumab-­‐ IL-­‐17A inhibitor •  Indica2ons: PSO •  Dosage-­‐80 mgs 2 SQ week 0, then 80 mgs 2,4,6,8,10,12 then Q 4 •  80 mgs monthly •  Side effect profile-­‐ slight up2ck in IBD associated symptoms in pts with IBD. •  TB screening •  Avoid live vaccines •  Pregnancy no data •  Secukinumab-­‐ IL-­‐17A inhibitor •  Indica2ons: AS, PSO, PSA •  Dosage-­‐150 mgs Q 1 week for 4 as induc2on •  Then 150 mgs monthly •  Side effect profile-­‐ same as TNF inhibitors •  TB screening •  Avoid live vaccines •  Pregnancy category B APCs
APCs
All approved for RA but no significant results in AS¹˗³ 1. Davis JC Jr, et al. Athri,s Rheum. 2007;57:1050-­‐1057. 2. Furst DE, et al. Rheumatology. 2013;52: 1845-­‐1855. 3. Deodhar A, et al. Arthri,s Care and Res.2010;62: 1266-­‐1271. 4. Visvanathan S. et al. Ann Rheum Dis. 2009;68(2):175-­‐182. 5. Dougados M, et al. Ann Rheum Dis. 2011;70(5): 799-­‐804 HLA
•  Abatacept •  Rituximab •  Tocilizumab •  Tofaci2nib Similar in efficacy T-cell inhibitor
abatacept
•  Other Biologic Response Modifiers TNF INHIBITORS
Chondrocytes
IL-6 Tocilizumab
Secukinumab IL-17a
Production of collagenase and other neutral
proteases
JAK inhibitors Small
molecules
Tofacitinib
Adapted from Arend WP et al. Arthritis Rheum. 1990;33:305-315.
•  Pa2ent educa2on •  Regular exercise •  Physical therapy land or water based •  Pa2ent associa2on and self help groups may be useful •  Extra-­‐ar2cular manifesta2ons psoriasis, uvei2s, IBD should be managed with collabora2on of appropriate specialists •  Rheumatologists and PC should be aware of increased CV risk and Osteoporosis risk Immuniza3ons in SpA Primary Care Rheumatology
2010 ASAS/EULAR Recommenda3on for Management of AS
NSAIDS •  SpA pa2ents have reduced responses to immuniza2ons; medica2ons may blunt these responses further Peripheral joint involvement •  No evidence that vaccina2ons exacerbate or precipitate rheuma2c disease Sulfasalazine •  Influenza and pneumococcal vaccina2ons are recommended Surgery Local steroid injec2ons Analgesics 1. Pt educa2on 2. Exercise 3. Physical therapy 4. Rehabilita2on 5. Pt associa2ons and self help groups Axial involvement •  Pos2mmuniza2on 2ters may be lower TNF Antagonists IL-­‐17A •  Hepa22s B immuniza2on if appropriate Ravikumar R, et al. Curr Rheumatol Rep. 2007 Oct;9(5):407-415.
CDC. MMWR. 2004;53(1):Q1-Q4.
Avery RK. Rheum Dis Clin North Am. 1999 Aug;25(3):567-584.
Chalmers A, et al. J Rheumatol. 1994;21(7):1203-1206.
Harpaz R, et al. MMWR Recomm Rep. 2008;57(RR-5):1-30.
Herpes zoster (shingles) vaccine guidelines for immunocompromised patients. American College of Rheumatology web site. http://
www.rheumatology.org/publications/hotline/2008_08_01_shingles.asp.
Immuniza3ons in SpA Primary Care Rheumatology
How do you make the diagnosis of SpA?
•  Several important key factors: •  You must think of it in any pt. male or female who has chronic low back pain. Have the pt point to the pain and decide clinically where it is. •  The history is key, labs and imaging are also helpful •  Live virus vaccines should be avoided in pa2ents on immunomodulators: •  Intranasal influenza, mumps/measles/rubella (MMR), yellow fever, typhoid, oral polio •  Wait at least 2 weeks aner giving these vaccines before ini2a2ng immunomodulators •  Zoster vaccine should be avoided in pa2ents on biologic agents •  May be given to pa2ents on MTX and prednisone <20 mg/d • 
• 
• 
• 
• 
•  Other immuniza2ons are safe: •  Influenza (injec2on), tetanus, pneumococcus, meningococcus, hepa22s A, hepa22s B, H. influenzae B (HiB), human papillomavirus (HPV) Ravikumar R, et al. Curr Rheumatol Rep. 2007 Oct;9(5):407-415.
CDC. MMWR. 2004;53(1):Q1-Q4.
Avery RK. Rheum Dis Clin North Am. 1999 Aug;25(3):567-584.
Chalmers A, et al. J Rheumatol. 1994;21(7):1203-1206.
Harpaz R, et al. MMWR Recomm Rep. 2008;57(RR-5):1-30.
Herpes zoster (shingles) vaccine guidelines for immunocompromised patients. American College of Rheumatology web site. http://
51
www.rheumatology.org/publications/hotline/2008_08_01_shingles.asp.
Personalize treatment is possible with improved understanding of the gene2cs and baseline characteris2cs that can predict response. Ask the ques2ons-­‐IBD, iri2s, psoriasis, FMHx, inflammatory back pain Get labs including HLA-­‐B27 Order an SIJ film and if nega2ve with a high suspicion then order MRI Try NSAIDs and if no response then refer Consider referral to rheum for dactyli2s, migratory joint pain and psoriasis, inflammatory back pain, enthesi2s, FmHx of SpA, iri2s, or unexplained erosions seen on x-­‐ray evalua2on. Thank You! Ques3ons? Tasks ahead unanswered ques3ons
•  With earlier detec2on can we alter the disease and damage it does? •  MRI scanning of SI joints can be vital in earlier diagnosis •  Are NSAIDs and TNF inhibi2on the best way to achieve remission as defined by preven2ng osteoprolifera2on and fat infiltra2on? 50
Ques2ons? Rick Pope Address ques2ons to: [email protected] Dept of Rheumatology Western CT Health Network References
•  www.the-­‐rheumatologist.org/details/ar2cle/6139751 Rheumatologist Make Progress defining the spectrum of axial spondyloarthri2s Atul Deodhar MD •  Google images •  American College of Rheumatology-­‐rheumatology.org •  Advanced Rheumatology Course on Spondyloarthri2s Diagnosis of SpondyloArthritis SpA
Diagnosis of SponydyloArthritis SpA
Is there infammtory back pain? > 2 of the 4 of the following • 
• 
• 
• 
Causes awakening in the 2nd half of the night Morning s2ffnes > 30 minutes Improves with exercise and not rest Alterna2ng bumock pain Yes Are there criteria for AS? •  Sacroilii2s on plain film or MRI plus one or more -­‐Inflammatory back pain -­‐Limited spinal mo2on on sagimal and frontal planes -­‐Limited chest expansion Is there evidence of Psoriasis or IBD? Unlikely to be spondyloarthri2s Enteropathic or IBD spondyloarthri2s Yes No Ankylosing SpondyliCs Yes Reac2ve Arhtri2s No Is there evidence of Psoriasis or IBD? Yes No Yes No Any antecedent infec2on compa2ble with ReA, GI or GU Infec2on? + stool or genital analysis or + Serology for Shigella, Salmonella, chlamydia, campylobacter, or C Difficile Yes No No Is there peripheral joint synovi2s that is asymmetric or predominately in the lower extremi2es Is there evidence of Inflammatory bowel disease, psoriasis? Is there at least one or more of the following: specificity increases with increasing number -­‐Sacroilii2s by imaging -­‐Enthesopathy Yes -­‐Bumock pain -­‐Dactyli2s Undifferen2ated SpA -­‐Iri2s -­‐Family Hx of IBD, psoriasis, AS, or any SpA Enteropathic or IBD spondyloarthri2s -­‐HLA B-­‐27 If No then consider other diagnosis And observe going forward Con2nued on next slide Systemic Biologic Therapies: Moderate to
Severe Psoriatic Disease
Systemic Biologic Therapies: Moderate to Severe
Psoriatic Disease (cont’d)
TNF-α inhibitors
TNF-α inhibitors
Studies
Common AEs
Black Box Warning
Etanercept
(psoriasis,
PsA)
PASI 75 after 12-24 wk ~50%;
>3 years of clinical data show
maintenance of effect
Injection site reaction,
+ANA
Infection, malignancies
Adalimumab
(psoriasis,
PsA)
After 16 weeks, ~80% of
patients had PASI 75
response; response
maintained over 2 years
Injection site reaction,
+ANA, elevated alkaline
phosphatase,
cholesterol
Infection, malignancies
Infliximab
(psoriasis,
PsA)
3 major trials assessing
efficacy; at week 10, 80%
(242/301) of patients treated
with infliximab achieved PASI
75 response; after
maintenance phase, patients
maintained PASI 75
Infusion reactions,
+ANA, elevated LFTs,
neutralizing antibodies
Infection,
hepatosplenic T-cell
lymphoma
Studies
Common AEs
Black Box Warning
Golimumab
(PsA only)
Effective in maintaining clinical
improvement through 5 years
URIs,
nasopharyngitis,
injection site
reactions
Serious infections,
malignancies
Certolizumab
pegol (PsA
only)
Phase 3 trial: 200 mg every other
week resulted in greater reduction
in radiographic progression vs
placebo at week 24 (ACR 20 60%
vs 20% with placebo)
URIs, rash,
urinary tract
infections
Serious infections,
malignancy
IL-12/-23 Inhibitor
Ustekinumab
(psoriasis,
PsA)
2 phase 3 clinical trials:
33% of patients achieved PASI 75
after 12 weeks
Nasopharyngitis
No
URIs = upper respiratory infections.
AEs = adverse events; LFTs = liver function tests; TB = tuberculosis.
Kupetsky E, et al. J Am Board Fam Med. 2013;26:787-801; Kavanaugh A, et al. Ann Rheum Dis.
2014;73:1689-1694; Moore AY et al. Clin Cosmet Investig Dermatol. 2010;3:49-58.
Simponi [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2015; Cimzia [prescribing
information]. Smyrna, GA: UCB Inc.; 2013; Satelar [prescribing information]. Horsham, PA: Janssen
Biotech, Inc.; 2014.
Systemic Biologic Therapies: (Moderate to
Severe Psoriatic Disease) (cont’d)
Screening Before Starting a Biologic
• 
IL-17A inhibitors
Studies
Common AEs
Black Box Warning
Secukinumab 4 clinical trials; with
(psoriasis,
300 mg 82% of patients
PsA)
achieved PASI 75 after
12 weeks, 81% of
whom maintained PASI
75 at 52 weeks
Nasopharyngitis,
diarrhea, URIs;
continued vigilance
with respect to the
potential for candida
infection needed
No
Ixekizumab
(psoriasis
only)
Injection site
reactions, URIs,
nausea, tinea
infections
No 3 clinical trials, >3800
patients; at 12 weeks,
87%-90% of patients
had 75% improvement
in PASI score; response
maintained in 75%
Initial assessment of
immunization status or disease
history
–  Haemophilus influenzae
• 
–  Tetanus
–  Chemistry screen + LFTs:
baseline and every 3-4 months
–  Pertussis
–  Varicella zoster
Cosentyx [prescribing information]. East Hanover, NJ: Novartis; 2016; Taltz [prescribing
information]. Indianapolis, IN: Eli Lilly & Co.; 2016.
Inflammatory Back Pain Chronic IBP is the leading symptom in pa2ents with axial SpA, including pa2ents with AS TNF-α inhibitors
–  Complete blood count +
platelets: baseline and every
2-6 months
–  Hepatitis A and B virus
• 
–  Human papillomavirus
–  Streptococcus pneumoniae
–  TB skin test: baseline and
annually thereafter
Ustekinumab
–  TB skin test: baseline
•  Secukinumab, ixekizumab
–  TB skin test: baseline
Lebwohl M, et al. J Am Acad Dermatol. 2008;58:94-105; Stelara [prescribing information].
Horsham, PA: Janssen Biotech; 2013; Wine-Lee L, et al. J Am Acad Dermatol.
2013;69:1003-1013; Taltz [prescribing information]. Indianapolis, IN: Eli Lilly; 2016.
Catabolic and Anabolic erosive and prolifera3ve
In pa2ents with chronic back pain (> 3 mo), IBP criteria are fulfulled if at least 4 out of 5 parameters are present • I nsidious onset • P ain at night (with improvement on arising) • A ge of onset (< 40 years) • I mprovement with exercise • N o improvement with rest Odds ra2o = 12.7 Odds ra2o= 20.4 Odds ra2o = 9.9 Odds ra2o = 23.1 Odds ra2o = 7.7 New concepts and treatments in SpA Summary
•  2 Key features: inflamma2on at enthesis •  New bone forma2on in the SIJ •  SpA es2mated prevalence higher than RA in US •  Associa2on with HLA-­‐B27 varies in different forms and popula2ons •  MRI can be valuable in visualizing SpA in the SIJ •  Inflammatory back pain consider referral to Rheumatologist •  Average delay in diagnosis is now 5-­‐11 years •  Earlier diagnosis and management can diminish severity and make a meaningful difference for the pa2ent Famous people with Ankylosing Spondyli3s Norman Cousins
Cousins was diagnosed with a form AS then known as Marie-­‐
Strumpell's disease. His struggle is detailed in the book and movie Anatomy Of An Illness. Norman Cousins (June 24, 1915 – November 30, 1990) American poli2cal journalist Author professor world peace advocate Factors that may predict long term
disease outcomes in SpA, including AS
Factors observed during first 2 yrs of disease •  For a SpA pa2ent with either Hip arthri2s •  Or > 3 of the following ESR > 30 mm/hr Poor efficacy of NSAIDs Limita2on of lumbar spine Sausage shaped finger or toe Oligoarthri2s Onset < 16 years Predicts severe outcome (sensi2vity 50% Specificity 97.5%) •  The absence of these factor during the first 2 years of disease was predic2ve of a mild outcome (sensi2vity, 92.5%; specificity, 78%) •  Of the 328 pa2ents with SpA enrolled in the studies, 151 pa2ents had follow up for > 10 years.