Myositis and Autoimmune ILD - azrheum.org
Transcript of Myositis and Autoimmune ILD - azrheum.org
![Page 1: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/1.jpg)
Myositis and Autoimmune ILD
2018 AURA Annual Meeting Sedona, Arizona
June 2, 2018
Chester V. Oddis, MD Director, Myositis Center University of Pittsburgh
![Page 2: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/2.jpg)
Disclosures
• Genentech: Clinical trial support • Idera: Clinical trial participant • Mallinckrodt: Clinical trial support; Advisory
Board
![Page 3: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/3.jpg)
Lecture Objectives • Discuss selected clinical features of myositis
classification.
• Discuss spectrum of autoantibodies seen in patients with myositis and their clinical associations
• Discuss selected treatment aspects of myositis and autoimmune ILD
![Page 4: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/4.jpg)
Classification of Myositis
• Adult polymyositis • Adult dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another AI disease • Inclusion body myositis (IBM)
![Page 5: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/5.jpg)
IIM: Diagnostic Criteria Bohan and Peter (1975)
• Symmetric proximal muscle weakness • Elevation of serum muscle enzymes: CK, aldolase, AST, ALT, LDH • Myopathic electromyographic abnormalities: sharp waves,
fibrillations, polyphasic motor units, high frequency repetitive discharges
• Characteristic muscle pathology: myofiber
degeneration/regeneration, MNC infiltrates, perifascicular atrophy
![Page 6: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/6.jpg)
Rashes of Dermatomyositis Rashes of Dermatomyositis
![Page 7: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/7.jpg)
Cuticular Thickening and
Periungual Erythema
Nail fold capillary abnormality
![Page 8: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/8.jpg)
Classification of Myositis
• Adult polymyositis • Adult dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another AI disease • Inclusion body myositis (IBM)
![Page 9: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/9.jpg)
Classification of Myositis
• Adult polymyositis • Adult dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another AI disease • Inclusion body myositis (IBM)
![Page 10: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/10.jpg)
• Endocrine myopathies hyper/hypothyroid
• Drug or toxic myopathies
• Metabolic myopathies
• Mitochondrial myopathies
• Muscular dystrophies
• Infectious myositis
• Neuropathies/neurologic syndromes
• Paraneoplastic syndromes
• Other connective tissue disorders
• Miscellaneous amyloid, sarcoid
Polymyositis Mimics
![Page 11: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/11.jpg)
Muscle Biopsy is a Must in “Polymyositis “ (unlike classic DM)
![Page 12: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/12.jpg)
Classification of Myositis • Adult polymyositis • Adult dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another AI
disease • Inclusion body myositis (IBM) • Necrotizing myopathy (NM)
What we called PM before, in some cases, is now called NM
![Page 13: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/13.jpg)
Neurology, 2003
![Page 14: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/14.jpg)
Classification of Myositis • Adult polymyositis
• Adult dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another AI
disease • Inclusion body myositis (IBM) • Necrotizing myopathy (NM)
What we called PM before, in some cases, is now called NM
![Page 15: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/15.jpg)
Medicine, 2005
![Page 16: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/16.jpg)
Classification of Myositis • Adult polymyositis
• Adult dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis
• Myositis in overlap with another AI disease
• Inclusion body myositis (IBM) • Necrotizing myopathy (NM)
What we called PM before, in some cases, is now called NM
![Page 17: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/17.jpg)
Lundberg et al, Ann RD, 2018
• For patients without classic DM rashes, do a muscle biopsy.
• For DM patients without muscle involvement do a skin biopsy.
• These criteria provide a score and probability for having IIM (for clinical trial purposes)
![Page 18: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/18.jpg)
Case One
• 67 year old Caucasian female with HTN, hyperlipidemia, uterine cancer (1997)
• July, 2004: atorvastatin
• June, 2008: lower extremity weakness
• Spring, 2009: difficulty walking up steps and lifting arms overhead
• June, 2009: stops atorvastatin on her own but no improvement in weakness
• September, 2009: CK 6473, repeat 9375
• Admitted to hospital; muscle biopsy: myonecrosis, no inflammation or vasculitis
![Page 19: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/19.jpg)
Necrotizing Myopathy
Kassardjian, JAMA Neurol, 2015
![Page 20: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/20.jpg)
Case One
• 67 year old Caucasian female with HTN, hyperlipidemia, uterine cancer (1997)
• July, 2004: atorvastatin
• June, 2008: lower extremity weakness • Spring, 2009: difficulty walking up steps and lifting arms
overhead • June, 2009: stops atorvastatin on her own but no improvement
in weakness
• September, 2009: CK 6473, repeat 9375; ANA 1:320 (H) • Admitted to hospital; muscle biopsy: myonecrosis, no
inflammation or vasculitis • Treated with prednisone (60mg/day) and CK and weakness
improve
![Page 21: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/21.jpg)
Case One • March, 2010 (1st UPMC visit)
– CK 5800 (increasing as prednisone tapered) – No other autoimmune manifestations; no FH of
autoimmune diseases – No rashes of dermatomyositis – Deltoids 4+/5; neck flexors 4/5; iliopsoas 3+/5
• Statin myopathy
• Pt hesitant to increase prednisone
![Page 22: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/22.jpg)
Immune-Mediated Necrotizing Myopathy Associated with Statins
• Proximal weakness during or after statin use • Elevated CK • Persistent weakness and elevated CK despite
stopping the statin • Improvement with IS agents • Muscle biopsy showing necrotizing myopathy
without significant inflammation
Grable-Esposito, Muscle & Nerve, 2010
![Page 23: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/23.jpg)
Anti-200/100 kD AutoAb Defines Subgroup of Necrotizing Myopathy (NM)
• 16/38 patient sera with NM had the doublet – All were weak with high CK – 63% had statin exposure prior
to weakness – 83% >age 50 exposed to
statins – All responded to IS therapy
and many relapsed
Christopher-Stine, Arth Rheum, 2010
Controls in lanes 5 and 10
![Page 24: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/24.jpg)
Statin Necrotizing Myopathy
• HMGCR was identified as the 100-kd autoantigenic target • Developed an ELISA for anti-HMGCR autoAb
– All 16 doublet positive pts were anti-HMGCR (+)
– 45/750 (6%) of cohort were anti-HMGCR (+)
Mammen, Arth Rheum, 2011
![Page 25: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/25.jpg)
Case One • April-June, 2010: worse weakness; CK 6367
• July, 2010: prednisone increased (60mg/d) and mtx added
• Jan, 2011: added imuran/mtx (25mg/week), pred 30mg/d
• May, 2011: added IVIg; continued other IS agents
• August, 2011: clearly improved with first normal CK in July
• November, 2011: 5/5 strength; taper IVIg (never off completely)
• March, 2012: stopped imuran
• June, 2012: off prednisone
• Progressive rise of CK 2013 – 2017; went back on mtx and IVIg; CK still elevated
![Page 26: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/26.jpg)
Case One • April-June, 2010: worse weakness; CK 6367
• July, 2010: prednisone increased (60mg/d) and mtx added
• Jan, 2011: added imuran/mtx (25mg/week), pred 30mg/d
• May, 2011: added IVIg; continued other IS agents
• August, 2011: clearly improved with first normal CK in July
• November, 2011: 5/5 strength; taper IVIg (never off completely)
• March, 2012: stopped imuran
• June, 2012: off prednisone
• Progressive rise of CK 2013 – 2017; went back on mtx and IVIg; CK still elevated
Pt is anti-HMGCR autoAb positive
![Page 27: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/27.jpg)
Features of Anti-SRP Subset • Acute onset of severe weakness with
myalgias; high CK • Necrotizing myopathy (or PM phenotype)
– no DM rash; ILD rare • Poor response to therapy with variable
prognosis
Refractory, persistently high CK, “dystrophy-like”
![Page 28: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/28.jpg)
Muscle Pathology of SRP Antibody Subset
• Necrotizing myopathy without inflammation
Dimitri, Muscle and Nerve, 2007
![Page 29: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/29.jpg)
Classification of Myositis • Adult polymyositis • Adult dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another AI disease • Inclusion body myositis (IBM) • Necrotizing myopathy (NM)
– Anti-HMGCR – Anti-SRP
![Page 30: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/30.jpg)
Classification of Myositis • Adult polymyositis • Adult dermatomyositis
– Amyopathic Dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another AI disease • Inclusion body myositis (IBM) • Necrotizing myopathy (NM)
– Anti-HMGCR – Anti-SRP
![Page 31: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/31.jpg)
Sometimes the skin
disease can be the most
dominant feature
![Page 32: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/32.jpg)
![Page 33: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/33.jpg)
DM Scalp Rash
![Page 34: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/34.jpg)
Treatment of DM Cutaneous Disease
Sun-protective measures; avoid photosensitive meds Topical GC (potency depends on severity) Topical calcineurin inhibitors (tacrolimus, pimecrolimus) Antimalarials (hydroxychloroquine or chloroquine); some dermatologists add quinacrine Oral glucocorticoids (varying doses)
2nd Line
Methotrexate (oral/SQ) MMF
3rd Line
IVIG Tacrolimus Cyclophosphamide Rituximab
Taper prednisone by 20-25% monthly to minimum
effective dose
Yes No
Clinical Response after 1-3 months?
![Page 35: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/35.jpg)
Apremilast in DM
50 yo woman failing GC, HCQ, aza, aza/mtx, MMF, IVIg, tacrolimus, dapsone and Acthar gel After 3 months
![Page 36: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/36.jpg)
Tofacitinib in DM: Case 1
• 55 yo female • Failed or partially responsive to GC, mtx,
HCQ, aza, MMF, chloroquine, Acthar gel, tacrolimus, IVIg
3 months
![Page 37: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/37.jpg)
Tofacitinib in DM: Case 2
• 67 yo woman with rash and arthritis
• Refractory to GC, mtx, HCQ, MMF, tacrolimus and Acthar gel
• Continued IVIg • DM rash inactive (0/10)
after 6 months
![Page 38: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/38.jpg)
Tofacitinib in DM: Case 3
• 42 yo Caucasian male • Rash and polyarthritis • Previous mtx, MMF, HCQ, aza, intolerant to IVIg • After 3 months rash and polyarthritis improved
![Page 39: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/39.jpg)
Treatment of DM Cutaneous Disease
Sun-protective measures; avoid photosensitive meds Topical GC (potency depends on severity) Topical calcineurin inhibitors (tacrolimus, pimecrolimus) Antimalarials (hydroxychloroquine or chloroquine); some dermatologists add quinacrine Oral glucocorticoids (varying doses)
2nd Line
Methotrexate (oral/SQ) MMF
3rd Line
IVIG Tacrolimus Cyclophosphamide Rituximab
Taper prednisone by 20-25% monthly to minimum
effective dose
Yes No
Clinical Response after 1-3 months?
4th Line Tofacitinib Apremilast
![Page 40: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/40.jpg)
Myositis specific autoantibodies Clinical phenotypes in adults and children
Myositis-specific autoantibodies
Anti-synthetases
PL-12 OJ KS
PL-7
EJ
Jo-1
Zo
YRS
Anti-SRP
Anti-HMGCR Anti-MDA-5
Anti-SAE Anti-NXP-2
Anti-Mi-2 Anti-TIF1g
Necrotizing
myopathy
High CK
Amyopathic
dermatomyositis
Rash sine myositis
Hypomyopathic
Rash precedes myositis
Dermatomyositis
Rash
Malignancy
Calcinosis/vasculitis (children)
Anti-synthetase syndrome
Fever
Raynauds
Lung fibrosis
Myositis
Arthropathy
Mechanics hands
+/- DM rash
Slide courtesy of Drs. Chinoy and Gunawardena
X
![Page 41: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/41.jpg)
Anti-CADM-140 (anti-MDA-5)
• Amyopathic DM with rapidly progressive ILD in Japanese (Sato, Arth Rheum, 2005 and 2009)
• Acute/subacute interstitial pneumonitis in DM in Chinese (Chen, Rheum Int, 2011)
• Also described in other Asian populations with similar phenotype
• Target autoantigen is MDA-5. What is MDA-5? – Cytoplasmic protein that “senses” viral RNA and induces
production of type I interferon
– Involved in innate immune defense against viruses
![Page 42: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/42.jpg)
Anti-CADM-140 (anti-MDA-5)
• Amyopathic DM with rapidly progressive ILD in Japanese (Sato, Arth Rheum, 2005 and 2009)
• Acute/subacute interstitial pneumonitis in DM in Chinese (Chen, Rheum Int, 2011)
• Also described in other Asian populations with similar phenotype
• Target autoantigen is MDA-5. What is MDA-5? – Cytoplasmic protein that “senses” viral RNA and induces
production of type I interferon
– Involved in innate immune defense against viruses
Supports role of a viral trigger
![Page 43: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/43.jpg)
Anti-MDA-5
• Novel cutaneous phenotype of palmar papules and cutaneous ulcerations – severe vasculopathy
Fiorentino, J Am Acad Derm, 2011
![Page 44: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/44.jpg)
Case Two
• Summer, 2012: Photosensitive rash in 58 yo WF
• January, 2013: Polyarthritis; mild muscle weakness; rash of DM – nl CK; Jo-1, ANA and SSA/B – all negative
– improves on low dose prednisone/mtx
• May, 2013: DM rashes worse; faint basilar crackles on exam (no pulmonary sx); mild weakness – Recommended 20mg prednisone and MMF – HRCT/PFTs
![Page 45: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/45.jpg)
June 6
![Page 46: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/46.jpg)
Case Two
• July 1: Presents to local ED “feeling very SOB”
• CXR ‘opacified’
• In one day, she is up to 12 liters/min O2
• Contacted by rheumatologist – Rash a little different
![Page 47: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/47.jpg)
![Page 48: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/48.jpg)
Case Two
• July 1: Presents to local ED “feeling very SOB”
• CXR ‘opacified’
• In one day, she is up to 12 liters/min O2
• Contacted by rheumatologist – Rash a little different
• Recommend pulse steroids, cytoxan and rituximab
![Page 49: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/49.jpg)
July 2
![Page 50: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/50.jpg)
July 2
June 6
![Page 51: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/51.jpg)
July 2
June 6
Anti- MDA-5 positive
![Page 52: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/52.jpg)
Anti-MDA-5 Positivity is Associated with a Poor Pulmonary Outcome
p<0.001
MDA5 (-) (n=106)
MDA5 (+) (n=16)
Moghadam-Kia, Arth Care Rsch, 2016
![Page 53: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/53.jpg)
Myositis specific autoantibodies Clinical phenotypes in adults and children
Myositis-specific autoantibodies
Anti-synthetases
PL-12 OJ KS
PL-7
EJ
Jo-1
Zo
YRS
Anti-SRP
Anti-HMGCR Anti-MDA-5
Anti-SAE Anti-NXP-2
Anti-Mi-2 Anti-TIF1g
Necrotizing
myopathy
High CK
Amyopathic
dermatomyositis
Rash sine myositis
Hypomyopathic
Rash precedes myositis
Dermatomyositis
Rash
Malignancy
Calcinosis/vasculitis (children)
Anti-synthetase syndrome
Fever
Raynauds
Lung fibrosis
Myositis
Arthropathy
Mechanics hands
+/- DM rash
Slide courtesy of Drs. Chinoy and Gunawardena
X X
![Page 54: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/54.jpg)
Anti-synthetase Syndrome
• Defines a clinically homogeneous patient population: – Fever – Myositis – Arthritis (misdiagnosed as RA) – Raynaud phenomenon – Mechanic’s hands – ILD
![Page 55: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/55.jpg)
Clinical Features: Anti-synthetase Syndrome
![Page 56: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/56.jpg)
But … the skin rash(es) and the myositis
may be subtle and the clinical
presentation may be ‘lung dominant’
![Page 57: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/57.jpg)
Case Three • 1/2001: 39 yo WF admitted to hospital with 5
weeks of fever (103-1040) and myalgias; extensive w/u negative except for low titer ANA and mild basilar fibrosis; leaves hospital with FUO frustrated by lack of diagnosis
![Page 58: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/58.jpg)
Case Three • 1/2001: 39 yo WF admitted with 5 weeks of
fever (103-1040) and myalgias; extensive w/u negative except for low titer ANA and mild basilar fibrosis; leaves hospital with FUO frustrated by lack of diagnosis
• 3/2001 (office): worsening myalgias and arthralgias, small pleural effusions, fever, Raynaud phenomenon. Dx as UCTD and given empiric prednisone
![Page 59: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/59.jpg)
Case Three • 1/2001: 39 yo WF admitted with 5 weeks of fever
(103-1040) and myalgias; extensive w/u negative except for low titer ANA and mild basilar fibrosis; leaves hospital with FUO frustrated by lack of diagnosis
• 3/2001 (office): worsening myalgias and arthralgias, small pleural effusions, fever, Raynaud phenomenon. Dx as UCTD and given empiric prednisone
• 4/2001: Increased SOB with more prominent diffuse pulmonary infiltrates; subtle Gottron changes; anti-PL-12 autoantibody identified
![Page 60: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/60.jpg)
Case Three: Subsequent Course • Worsening infiltrates and deteriorating PFTs
– PFTs: FVC 56%, FEV-1 52%, DLCO 40%
• Responded to glucocorticoids and tacrolimus
• Skin rash, joint symptoms and fever never return
• Never developed myositis
• Raynaud is mild and most recent PFTs (1/2018) – FVC 75%; FEV-1 87%; DLCO 78% – Echo with nl PAS (25mmHg)
• Currently on tacrolimus, no prednisone
![Page 61: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/61.jpg)
Making the Diagnosis of Autoimmune ILD
Not everyone will present with the classic anti-synthetase
syndrome
![Page 62: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/62.jpg)
Anti-synthetase Autoantibodies
Antibody Antigen (tRNA synthetase)
Prevalence in IIM (%)
Jo-1
histidyl
20-30
PL-7 threonyl <5 PL-12 alanyl <5
OJ isoleucyl <5 EJ glycyl <5 KS asparaginyl <1 Tyr tyrosyl <1 Zo phenylalanyl < 1
![Page 63: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/63.jpg)
University of Pittsburgh Anti-Synthetase Cohort
Autoantibody Number (% synthetases) Jo-1 140 (60%)
PL-12 36 (16%) PL-7 27 (12%)
EJ 11 (5) OJ 6 (3) KS 9 (4)
Total Synthetases 229
![Page 64: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/64.jpg)
University of Pittsburgh Anti-Synthetase Cohort
Autoantibody Number (% synthetases) Jo-1 140 (60%)
PL-12 36 (16%) PL-7 27 (12%)
EJ 11 (5) OJ 6 (3) KS 9 (4)
Total Synthetases 229
![Page 65: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/65.jpg)
Initial CTD Diagnosis in Anti-Syn Cohort
Aggarwal, Ann Rheum Dis, 2014
DM 24%
17%
Jo-1 n=122
PM 22%
DM 17% Overlap or UCTD
48%
SSc 13%
Non-Jo-1 n=80
PM DM Overlap or UCTD SSc
PM 59%
![Page 66: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/66.jpg)
Initial CTD Diagnosis in Anti-Syn Cohort
Aggarwal, Ann Rheum Dis, 2014
DM 24%
17%
Jo-1 n=122
PM 22%
DM 17% Overlap or UCTD
48%
SSc 13%
Non-Jo-1 n=80
PM DM Overlap or UCTD SSc
PM 59%
Myositis UCTD/Overlap Scleroderma Jo-1 83% 17% 0% Non-Jo-1 39% 48% 13%
p<0.001
![Page 67: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/67.jpg)
Survival is worse in non Jo-1 than Jo-1 patients
Aggarwal, Ann Rheum Dis, 2014
Jo-1
non Jo-1
![Page 68: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/68.jpg)
Survival is worse in non Jo-1 than Jo-1 patients
Aggarwal, Ann Rheum Dis, 2014
Jo-1
non Jo-1
Jo-1 non Jo-1 p value
Diagnosis delay (years) 0.4 (0.2-0.8) 1.0 (0.4 – 5.1) <0.01
![Page 69: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/69.jpg)
Pulmonary fibrosis
49%
Pulmonary HTN 11%
CTD heart 5%
CTD kidney
3%
Cancer 9%
Infection 6%
Atherosclerosis 9%
Unknown 6%
Cause of Death in Anti-Synthetase Cohort
In synthetase (+) pts pulmonary disease was most common cause of death
Aggarwal, Ann Rheum Dis, 2014
![Page 70: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/70.jpg)
Synthetase Positive Patients: Jo-1 vs. non-Jo-1
• Non Jo-1 synthetase (+) patients frequently present with non-myositis symptoms … and may never manifest them.
• Diagnosis of a specific CTD is delayed in non-Jo-1 synthetase (+) patients – perhaps leading to worse survival.
• Synthetase (+) patients, whether Jo-1 or non Jo-1 have increased pulmonary morbidity and mortality.
![Page 71: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/71.jpg)
Classification of Myositis • Adult polymyositis • Adult dermatomyositis
– Amyopathic Dermatomyositis • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another AI disease • Inclusion body myositis (IBM) • Necrotizing myopathy (NM)
– Anti-HMGCR – Anti-SRP
![Page 72: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/72.jpg)
Are there autoantibody markers that identify patients with malignancy-
associated myositis?
![Page 73: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/73.jpg)
Anti-p155/140 (anti-TIF1-γ) Autoantibody
• Adults: Associated with severe cutaneous DM and cancer associated myositis
• JDM: Severe cutaneous involvement including ulceration, edema and calcinosis
• But cancer associated myositis is not seen in JDM
![Page 74: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/74.jpg)
But we were seeing patients with
TIF1-γ that did not have malignancy
![Page 75: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/75.jpg)
Aggarwal, Rheumatology, 2014
![Page 76: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/76.jpg)
Aggarwal, Rheumatology, 2014
![Page 77: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/77.jpg)
Do Quantitative TIF1-γ ELISA Titers
Predict Cancer Associated
Myositis?
![Page 78: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/78.jpg)
Anti-TIF1-γ Titers Predict Cancer
Aggarwal et al. ACR 2012
6 10 25 50
100 125
75 0
10
20
30
40
50
60
TIF1 negative TIF1 low positive (<50)
TIF1 high positive (≥50)
% with Cancer
p = 0.67
p = 0.0002
Cancer in Dermatomyositis
![Page 79: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/79.jpg)
Myositis specific autoantibodies Clinical phenotypes in adults and children
Myositis-specific autoantibodies
Anti-synthetases
PL-12 OJ KS
PL-7
EJ
Jo-1
Zo
YRS
Anti-SRP
Anti-HMGCR Anti-MDA-5
Anti-SAE Anti-NXP-2
Anti-Mi-2 Anti-TIF1g
Necrotizing
myopathy
High CK
Amyopathic
dermatomyositis
Rash sine myositis
Hypomyopathic
Rash precedes myositis
Dermatomyositis
Rash
Malignancy
Calcinosis/vasculitis (children)
Anti-synthetase syndrome
Fever
Raynauds
Lung fibrosis
Myositis
Arthropathy
Mechanics hands
+/- DM rash
Slide courtesy of Drs. Chinoy and Gunawardena
![Page 80: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/80.jpg)
Myositis Treatment:
Beyond Steroids, Methotrexate and
Azathioprine
![Page 81: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/81.jpg)
Combination Therapy in Myositis • Multiple reports of combination therapy in treatment
of refractory PM and DM
• Literature support for combination of methotrexate and azathioprine in IIM [Villalba, Arthritis Rheum, 1998]
– effective in treatment-resistant myositis
– beneficial in those who had failed either mtx or aza alone
• Also consider mtx/MMF combination (anecdotal)
![Page 82: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/82.jpg)
Mycophenolate Mofetil in Myositis (2-3 grams/day)
• 6 of 10 patients with DM successfully tapered CS with MMF [Rowin, Neurology, 2006] – 3 developed opportunistic infections (other risk factors)
• Improvement in cutaneous features in 10/12 DM patients [Edge, Arch Derm, 2006]
• IVIg as add-on therapy to MMF effective in 7 severe and refractory pts (4PM/3DM) [Danielli, Autoimmunity Rev, 2009] – Safe and steroid-sparing
• Retrospective review of 50 JDM pts using MMF for 12 months [Rouster-Stevens, Arth Care Rsch, 2010] – Improved skin and muscle and steroid-sparing; well-tolerated
![Page 83: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/83.jpg)
IVIg in Myositis • Literature review of 308 adult patients
– 14 articles – only 2 RCT
• Safe with tolerable adverse events • Steroid-sparing in setting of infection • Effective in esophageal involvement • “Acute” complications or rapidly progressive disease • Effective for refractory rash • Might be the drug of choice in statin-associated IMNM
Wang, Clin Rheumatol, 2012
![Page 84: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/84.jpg)
Rituximab in Myositis Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis
Chester V. Oddis, MD Ann M. Reed, MD and the RIM Study Group
![Page 85: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/85.jpg)
RIM Trial Summary • Primary and secondary endpoints were not achieved
• 83% of refractory adult and juvenile myositis patients (n=200) met the Definition of Improvement in this trial
• There was a significant glucocorticoid sparing between the baseline dose and the dose at study conclusion
• Rituximab was generally well tolerated
Oddis, Arth Rheum, 2013
![Page 86: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/86.jpg)
Myositis Autoantibody Subsets Predict Response to Rituximab
Prob
abili
ty o
f Not
Mee
ting
DO
I
Primary and strongest predictors of response
were Jo-1 and Mi-2
Aggarwal, A&R, 2014
![Page 87: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/87.jpg)
Biologic Agents in Myositis: Selected Trials
Oddis & Aggarwal, Nat. Rev. Rheumatol, 2018
![Page 88: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/88.jpg)
IL-6 Blockade in Murine Model of PM
• IL-6 critically involved in development of myositis and muscles expressed IL-6
• Treatment with tocilizumab was effective in amelioration of myositis
Okiyama & Kohsaka, Arth Rheum, 2009
![Page 89: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/89.jpg)
Tocilizumab in the Treatment of Refractory Polymyositis and
Dermatomyositis
![Page 90: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/90.jpg)
Biologic Agents in Myositis: Selected Trials
Oddis & Aggarwal, Nat. Rev. Rheumatol, 2018
![Page 91: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/91.jpg)
Ann Rheum Dis, 2018
![Page 92: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/92.jpg)
Biologic Agents in Myositis: Selected Trials
Oddis & Aggarwal, Nat. Rev. Rheumatol, 2018
![Page 93: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/93.jpg)
Is Anti-T cell Therapy Rational in Myositis-associated ILD?
![Page 94: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/94.jpg)
T cells as Therapeutic Targets in Myositis- Associated ILD
• Pathology: abundant lymphocytes and plasma cells in the lung of PM/DM pts (form lymphoid follicles)
![Page 95: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/95.jpg)
T cells as Therapeutic Targets in Myositis- Associated ILD
• Pathology: abundant lymphocytes and plasma cells in the lung of PM/DM pts (form lymphoid follicles)
• Infiltrating lymphocytes in myositis NSIP pts revealed “activated” CD8+ T-cells [Yamadori, Rheumatol Int, 2001]
![Page 96: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/96.jpg)
T cells as Therapeutic Targets in Myositis- Associated ILD
• Pathology: abundant lymphocytes and plasma cells in the lung of PM/DM pts (form lymphoid follicles)
• Infiltrating lymphocytes in myositis NSIP pts revealed “activated” CD8+ T-cells [Yamadori, Rheumatol Int, 2001]
• CD8+ and “activated” T-cells increased in BAL fluid of PM/DM pts (n=22) [Kurasawa, Clin Exp Immunol, 2002]
![Page 97: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/97.jpg)
T cells as Therapeutic Targets in Myositis- Associated ILD
• Pathology: abundant lymphocytes and plasma cells in the lung of PM/DM pts (form lymphoid follicles)
• Infiltrating lymphocytes in myositis NSIP pts revealed “activated” CD8+ T-cells [Yamadori, Rheumatol Int, 2001]
• CD8+ and “activated” T-cells increased in BAL fluid of PM/DM pts (n=22) [Kurasawa, Clin Exp Immunol, 2002]
• Decrease in regulatory T cells in IP of CTD-ILD [Katigiri, Mod Rheumatol, 2008]
![Page 98: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/98.jpg)
T cells as Therapeutic Targets in Myositis- Associated ILD
• Pathology: abundant lymphocytes and plasma cells in the lung of PM/DM pts (form lymphoid follicles)
• Infiltrating lymphocytes in myositis NSIP pts revealed “activated” CD8+ T-cells [Yamadori, Rheumatol Int, 2001]
• CD8+ and “activated” T-cells increased in BAL fluid of PM/DM pts (n=22) [Kurasawa, Clin Exp Immunol, 2002]
• Decrease in regulatory T cells in IP of CTD-ILD [Katigiri, Mod Rheumatol, 2008] Implicates activated CD8+ T-cells in myositis-associated ILD
![Page 99: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/99.jpg)
Tacrolimus in Myositis and ILD
Parameter p-value FVC <0.0001 FEV-1 <0.0001 DLCO 0.0046 CK <0.0001 MMT 0.06 CS Dose <0.0001
Wilkes, Arth Rheum, 2005
Retrospective study of 13 synthetase (+) pts (12 with Jo-1)
![Page 100: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/100.jpg)
Anti-T cell Therapy in Myositis-associated ILD
• Accumulating data on efficacy of tacrolimus/CsA – Wilkes, Arth Rheum, 2005
– Takada, Autoimmunity, 2005
– Takada, Mod Rheumatol, 2007
– Guglielmo, Eur Respir J, 2009 ARDS reversed with tacrolimus
– Ando, Clin Rheumatol, 2010 ADM pt refractory to CsA responded to tacrolimus
![Page 101: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/101.jpg)
Anti-T cell Therapy in Myositis-associated ILD
• Accumulating data on efficacy of tacrolimus/CsA – Wilkes, Arth Rheum, 2005
– Takada, Autoimmunity, 2005
– Takada, Mod Rheumatol, 2007
– Guglielmo, Eur Respir J, 2009 ARDS reversed with tacrolimus
– Ando, Clin Rheumatol, 2010 ADM pt refractory to CsA responded to tacrolimus
Abatacept should also be studied in AILD
![Page 102: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/102.jpg)
Abatacept for the Treatment of Myositis-associated Interstitial Lung Disease (Attack My-ILD)
Proof-of-concept study: To evaluate the efficacy and safety of abatacept in myositis ILD; randomized, double blind, placebo-controlled 24-week trial followed by a 24-week open-label extension.
Sponsor: Bristol Myers Squibb
Principal investigator: Rohit Aggarwal
Co-investigators: Chester Oddis, Siamak Moghadam-Kia
![Page 103: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/103.jpg)
Long-term experience with rituximab in anti-synthetase
syndrome-related ILD (Andersson et al, Rheumatology, 2015)
Retrospective study
![Page 104: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/104.jpg)
112 Syn+ patients
34 Tx with Rtx
24/30 with 12 mth f/u
30 severe ILD
Long-term f/u Cohort
• 19 Jo-1; 3 PL-7; 2 PL-12 • 18/24 SSA (+) • Acute ILD in 50% • Median f/u from Rtx #1 = 52 mths (12-118) • Mean # Rtx cycles = 2.7 (1-11) • 8/24 received only 1 cycle • None got monotherapy with Rtx!!
Rtx generally 2-dose regimen at days 0, 14
![Page 105: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/105.jpg)
PFTs 24% 22% 17% % increase from
baseline
Andersson, Rheumatology, 2015
![Page 106: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/106.jpg)
HRCT: Lung Parenchymal Involvement
• Pre and Post Rtx scans in 23/24 • 50% to 33% [p<0.001] • In 5, ILD extent dropped >60% • 1 increased (transplanted)
Andersson, Rheumatology, 2015
![Page 107: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/107.jpg)
PLOS ONE; November, 2015
J Rheum, 2016
![Page 108: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/108.jpg)
Approach to treating myositis-associated ILD
Oddis & Aggarwal, Nat. Rev. Rheumatol, 2018
![Page 109: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/109.jpg)
Future Approaches to Guiding Therapy
• Take out the heterogeneity of myositis and study relevant disease subsets – Better to study autoAb subsets than clinical
subsets • Clinical/immunogenetic homogeneity • Perhaps even pathologic uniformity
• Sequential approach using different agents – Targeted biologic therapy
• Better exercise programs
![Page 110: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/110.jpg)
University of Pittsburgh Myositis Center and Collaborators
• Rheumatology ‒ Rohit Aggarwal, MD, MS ‒ Siamak Moghadam-Kia, MD ‒ Many fellows over the years
• Pulmonary ‒ Kevin Gibson, MD ‒ Kristen Veraldi, MD, PhD ‒ Daniel Kass, MD
• Neuropathology ‒ David Lacomis, MD
• Collaborators – Dana Ascherman, MD (U. Miami) – Japan
Masa Kuwana, MD, PhD Shinji Sato, MD
• Research Coordinators – Diane Koontz (database manager) – Many others
• CTD Research Laboratory – Zengbiao Qi
![Page 111: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/111.jpg)
Thank You
![Page 112: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/112.jpg)
![Page 113: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/113.jpg)
Pathologic Myositis Classification
Pestronk, Curr Opin Rheum, 2011
![Page 114: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/114.jpg)
Aggarwal, Ann Rheum Dis, 2017
![Page 115: Myositis and Autoimmune ILD - azrheum.org](https://reader031.fdocuments.net/reader031/viewer/2022012104/616a1ad511a7b741a34eda8c/html5/thumbnails/115.jpg)
Aggarwal, Ann Rheum Dis, 2017