Transcript Myositis Update: Treatment, Autoantibodies and More
Myositis Update: Treatment, Autoantibodies and More
Rare Disease Visiting Professor Grand Rounds Neurology/Neurosurgery University of Kansas Medical Center August 23, 2013 Chester V. Oddis, MD Division of Rheumatology and Clinical Immunology University of Pittsburgh
Disclosures
Questcor: Advisory Board
Lecture Objectives
• Discuss general myositis classification and autoantibodies • Discuss autoimmune ILD in myositis syndromes • Review selected treatments and discuss newer potential therapeutic options for myositis
Essentially none of the agents discussed today are “approved” for use in myositis
Conventional Classification of Myositis
• Adult polymyositis (PM) • Adult dermatomyositis (DM) • Juvenile myositis (DM >> PM) • Malignancy-associated myositis • Myositis in overlap with another autoimmune disease • Inclusion body myositis (IBM)
Gottron Papules
Rashes of Dermatomyositis Gottron Sign
Rashes of Dermatomyositis Heliotrope Rash
Rashes of Dermatomyositis Facial Rash
Conventional Classification of Myositis
• • • • • • Adult polymyositis (PM) Adult dermatomyositis (DM) Juvenile myositis (DM >> PM) Malignancy-associated myositis Myositis in overlap with another autoimmune disease Inclusion body myositis (IBM)
Polymyositis Mimics
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
Elevated Muscle Enzymes in the Absence of Muscle Disease • Demographics BM > BF > WM > WF Racial variation in serum CK Healthy asymptomatic blacks have higher serum CK levels than whites or Hispanics • Exercise/Manual Labor •
Idiopathic HyperCKemia
Johnston et al, JRSM, 1996 Prelle et al, J Neurol, 2002
We can classify pathologically
DM PM IBM NM
IIM Serologic Classification • • • “Myositis-specific” (MSA) – ARS (anti-synthetase) – – – – – – – Mi-2 CADM 140 (MDA-5) SAE MJ P155/140 (TIF1 γ) SRP HMG CoA reductase (statin NM) Myositis-associated (MAA) – anti-PM/Scl, Ku, U1/U2/U3RNP MSA/MAA negative
Myositis Autoantibody Subsets
Anti-Synthetases PL-7 PL-12
EJ
Mi-2 Jo-1 PM/NM HMGCR SRP TIF-1γ PM-Scl MDA-5 SAE MJ DM Overlap U1RNP Ku
Classification of Myositis
• • • • • • • Adult polymyositis Adult dermatomyositis – Amyopathic DM (ADM) Juvenile myositis (DM >> PM) Malignancy-associated myositis Myositis in overlap with another autoimmune disease Inclusion body myositis (IBM) Necrotizing myopathy – Statin/anti-SRP
Clinically Amyopathic DM (CADM)
• A subset of DM patients with cutaneous manifestations of DM for 6 months or longer • No proximal muscle weakness • May have elevated serum muscle enzymes, mild EMG abnormalities/biopsy findings
CADM = Amyopathic DM (ADM) + Hypomyopathic DM (HDM)
Malignancy and CADM
• Frequency of malignancy probably similar in CADM and classic DM – 41/291 (14%) in ADM review series (Gerami, 2006) – 15% in classic DM (Sigurgeirsson, NEJM, 1992) • Antibody positivity may not be “protective”
CADM and Lung Disease
• 19/197 (10%) ADM pts had ILD – review of literature • Challenge – They may be missed if the rash of DM is missed Gerami, J Am Acad Dermatol, 2006
Myositis Autoantibody Subsets
PL-7 PL-12
EJ
Mi-2 Jo-1 PM/NM HMGCR SRP TIF-1γ PM-Scl MDA-5 SAE MJ DM Overlap U1RNP Ku ADM
Anti-CADM-140 • 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?
– Involved in innate immune defense against viruses
Supports role of a viral trigger
Anti-CADM-140 • • Novel cutaneous phenotype of palmar papules and cutaneous ulcerations – severe vasculopathy Rapidly progressive ILD Fiorentino, J Am Acad Derm, 2011
Case One • • • • • • 70 year old WM “Double pneumonia” in 6/2012 Rash of DM in 9/2012 Vasculitic skin changes in 1/2013 No muscle weakness Cytoxan for ILD
Case Two
• Pt referred for “Amyopathic DM” • 44 yo WF with mild Gottron’s rash and periungual changes • Normal muscle enzymes (LDH 256) • Subtle iliopsoas weakness at 4+/5 • “Borderline” myopathic changes in deltoid
Percutaneous needle muscle biopsy
Case Two: Teaching Points
• Careful physical examination is important no subjective symptoms, nl CK, essentially nl EMG • Normal-CK, active myositis occurs! particularly dermatomyositis (juvenile and adult) other enzymes may also be normal • Muscle biopsy still helpful
• • • • • • • Case Three 41 y.o. white male with HTN, dyslipidemia 3/20: periorbital edema 3/27: acute polyarthritis 4/7: dyspnea, fever 4/11: admitted to outside hospital with bilateral pulmonary infiltrates 4/26: worsening dyspnea; unresponsive to antibiotics and steroids and transferred to UPMC 4/27: Post bronchoscopy and BAL/biopsy; dyspneic male with no history of muscle or lung problems; O 2 saturation 90% (100% O 2 mask/nasal cannula) ROS: no Raynauds, mild joint pain Exam: drug rash but no heliotrope or Gottron’s sign; diffuse rales; no synovitis; normal muscle strength Labs: CK 657; ANA negative ; other labs essentially normal
Anti-synthetase Syndrome • Defines a clinically homogeneous patient population – – – – – – Fever Myositis Arthritis (misdx as RA) Raynaud phenomenon Mechanic’s hands ILD
Myositis Autoantibody Subsets
Anti-synthetases PL-7 PL-12
EJ
Mi-2 Jo-1 PM/NM HMGCR SRP TIF-1γ PM-Scl MDA-5 SAE MJ DM Overlap U1RNP Ku
Anti-synthetase Autoantibodies Antibody Jo-1 PL-7 PL-12 OJ EJ KS Tyr Zo Antigen (tRNA synthetase) histidyl threonyl alanyl isoleucyl glycyl asparaginyl tyrosyl phenylalanyl Prevalence in IIM (%) 20-30 <5 <5 <5 <5 <1 <1 < 1
Myositis-Associated ILD
• 30-40% IIM patients have ILD – most commonly involved extramuscular organ • Significant contribution to morbidity/mortality
Strong association of ILD with all anti-synthetase autoAbs
Making the Diagnosis of Autoimmune ILD?
Not everyone will present with the classic anti-synthetase syndrome
Making the Diagnosis of Autoimmune ILD?
• Recognize ‘incomplete’ clinical syndromes ILD alone or ILD with subtle CTD findings
University of Pittsburgh Anti-synthetase Cohort
Autoantibody Jo-1 PL-12 PL-7 EJ OJ KS Total Synthetases Number (% synthetases) 140 (60%) 36 (16%) 27 (12%) 11 (5) 6 (3) 9 (4) 229
University of Pittsburgh Anti-synthetase Cohort
Autoantibody Jo-1 PL-12 PL-7 EJ OJ KS Total Synthetases Number (% synthetases) 140 (60%) 36 (16%) 27 (12%) 11 (5) 6 (3) 9 (4) 229
Initial CTD Symptom in Anti-syn Cohort
Raynaud’s Fatigue 4% 7%* Fever 2% Rash 4% Fatigue Fever 4% 3% Rash 4% Muscle 14%* Pulmonary 22% Muscle 30%* Raynaud’s 25%* Joint 13%* Joint 27%* Pulmonary 29% * p<0.02
Jo-1 (n=122) Other Anti-synthetases (n=80) Raynaud’s more common as initial symptom in non-Jo-1 subset - Muscle and joint less frequent initial symptom in non-Jo-1 subset
Aggarwal, Ann RD, 2013
Jo-1 vs. Other Synthetases: Clinical Presentation
Jo-1 (n=122) non-Jo-1 (n=80) p value Mean Age at Symptom Onset (yrs) % Female % Caucasian 45 46 NS 67 70 NS 86 79 NS Diagnoses at First Visit (%) Myositis Overlap or UCTD SSc 83 17 0 Median Delay in Dx from 1 st CTD Symptom (years; IQR) 0.4
(0.2-0.8) 40 48 13 1.0 (0.4-5.1) p<0.001
p<0.001
• •
In 60% of cases, non-Jo-1 pts did NOT have a myositis Dx at their initial visit Non-Jo-1 patients had a longer delay in Dx than Jo-1 patients
Aggarwal, Ann RD, 2013
Cause of Death in Anti-synthetase Cohort
Atherosclerosis 9% Infection 6% Cancer 9% CTD kidney 3% CTD heart 5% Pulmonary HTN 11% Unknown 6% Pulmonary fibrosis 49% - In synthetase (+) pts pulmonary disease was most common cause of death
Aggarwal, Ann RD, 2013
Jo-1 vs. Other Anti-synthetases: Outcome
Pulmonary Cause of Death Cumulative Survival % Fibrosis PAH Jo-1 (n=122) non-Jo-1 (n=80) p value 16/36 16/30 NS 3/36 4/30 5 year 90 75 10 year p<0.005
70 47 Median Survival (yrs) 15 9 p<0.01
• •
Pulmonary cause of death was similar between groups Non-Jo-1 pts had decreased survival compared to Jo-1 pts
Aggarwal, Ann RD, 2013
Making the Diagnosis of Autoimmune ILD?
• Recognize ‘incomplete’ clinical syndromes ILD alone or ILD with subtle CTD findings • ‘Myositis-specific Abs’ in the absence of myositis
Making the Diagnosis of Autoimmune ILD?
• Recognize ‘incomplete’ clinical syndromes ILD alone or ILD with subtle CTD findings • ‘Myositis-specific Abs’ in the absence of myositis • Negative ANA
• • • • • • • Case Three 41 y.o. white male with HTN, dyslipidemia 3/20: periorbital edema 3/27: acute polyarthritis 4/7: dyspnea, fever 4/11: admitted to outside hospital with bilateral pulmonary infiltrates 4/26: worsening dyspnea; unresponsive to antibiotics and steroids and transferred to UPMC 4/27: Post bronchoscopy and BAL/biopsy; dyspneic male with no history of muscle or lung problems; O 2 saturation 90% (100% O 2 mask/nasal cannula) ROS: no Raynauds, mild joint pain Exam: drug rash but no heliotrope or Gottron’s sign; diffuse rales; no synovitis; normal muscle strength Labs: CK 657; ANA negative ; other labs essentially normal
Anti-Jo-1 Autoantibody
• • Directed against histidyl-tRNA synthetase
Ag
Ag: enzyme that catalyzes binding of an amino acid to its tRNA in process of protein synthesis
histidine his tRNA syn tRNA for histidine
A Negative ANA Does Not Imply Antibody Negativity Homogeneous, diffuse
cytoplasmic
staining Dimitri, Muscle and Nerve, 2007
Frequency of ANA and Cytoplasmic Staining in Anti-synthetase Patients
Anti-Syn patients ANA + 100/199 (50%) Anti-CytAb + p value 142/196 (72%) p < 0.001
Aggarwal, ACR 2010
Frequency of ANA and Cytoplasmic Staining in Anti-synthetase Patients
ANA + Anti-CytAb + Anti-Syn patients
All Jo-1 All non-Jo-1
100/199 (50%) 142/196 (72%)
62/119 (52%) 38/80 (48%) 77/116 (66%) 65/80 (81%)
p value p < 0.001
p = 0.026
p < 0.001
Aggarwal, ACR 2010
Frequency of ANA and Cytoplasmic Staining in Anti-synthetase Patients
ANA + Anti-Syn patients
All Jo-1 All non-Jo-1
SSc 100/199 (50%)
62/119 (52%) 38/80 (48%) 1935/1946
(99%) Anti-CytAb + 142/196 (72%)
77/116 (66%) 65/80 (81%) 180/1946 (9%)
p value p < 0.001
p = 0.026
p < 0.001
Aggarwal, ACR 2010
How Can You Miss Autoimmune ILD?
• Failure to recognize ‘incomplete’ clinical syndromes • ‘Myositis-specific Abs’ in the absence of myositis aren’t ordered or not detected • Reassured by the negative ANA
Myositis Autoantibodies
Antibody CADM-140 Jo-1 Other anti-Syn Mi-2 Target MDA-5 ARS NuRD Subset DM PM/DM Phenotype Amyopathic, ILD Anti-synthetase syndrome DM Shawl, V-neck, Gottron’s
Myositis Autoantibodies
Antibody CADM-140 Jo-1 Other anti-Syn Mi-2 SAE MJ p155/140 SRP 200/100 kD Target MDA-5 ARS NuRD SUMO NXP-2 TIF1-
g
Signal recognition particle 72, 54 kDa HMGCR Subset DM PM/DM DM DM JDM DM, JDM PM IMNM Phenotype Amyopathic, ILD Anti-synthetase syndrome Shawl, V-neck, Gottron’s ILD, dysphagia Calcinosis, ulceration Severe skin, malignancy Severe/refractory necrotizing myositis Necrotizing myopathy
Myositis Treatment: Beyond Steroids, Methotrexate and Azathioprine
Pharmacologic Therapy of IIM
• • • • •
Corticosteroids Immunosuppressive Agents Combination regimens IVIg Biologic agents
Corticosteroids in Myositis
• • • • • • • Empirically remain initial treatment of choice Begin divided dose prednisone at 60 mg daily (30 mg bid) Continue until serum CK falls to normal Consolidate to single morning dose Taper by 25% existing dose q 3-4 weeks to 5-10 mg daily maintenance dose Continue until active disease suppressed one year Improvement in strength lags behind CK improvement
Pharmacologic Therapy of IIM
• • • • •
Corticosteroids Immunosuppressive Agents Combination regimens IVIg Biologic agents
Aggarwal/Oddis, Curr Rheum Rep, 2011
Pharmacologic Therapy of IIM
• • • • •
Corticosteroids Immunosuppressive Agents Combination regimens IVIg Biologic agents
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
IS Agents Beyond Mtx and Aza…
•
Mycophenolate mofetil
Mycophenolate Mofetil in Myositis • • • 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
IS Agents Beyond Mtx and Aza…
•
Mycophenolate mofetil
•
Cyclosporine/tacrolimus
•
Cyclophosphamide
Treatment of ILD in Myositis Patients
• Corticosteroids remain the initial treatment • Cyclophosphamide and azathioprine used early or in CS resistant cases with variable results Intermittent IV ctx pulse [Okada, Mod Rheumatol, 2007] • MMF in CTD-associated ILD [Swigris, Chest, 2006; Fischer, J Rheum, 2013] • Cyclosporine and tacrolimus used in both adult and pediatric patients with promising results
Tacrolimus in Myositis and ILD
Parameter FVC FEV-1 DLCO CK MMT CS Dose p-value
<0.0001
<0.0001
0.0046
<0.0001
0.06
<0.0001
Retrospective study of 13 synthetase (+) pts (12 with Jo-1)
Wilkes, Arth Rheum, 2005
Is Anti-T cell Therapy Rational in Myositis-associated ILD?
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
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 A
Abatacept should also be studied in AILD
Pharmacologic Therapy of IIM
• • • • •
Corticosteroids Immunosuppressive Agents Combination regimens IVIg Biologic agents
IVIg in Myositis
• Randomized, double-blind, placebo controlled study of 15 treatment-resistant DM patients demonstrated efficacy [Dalakas, NEJM, 1993] – No significant side effects; felt to be safe and effective for refractory DM
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 Wang, Clin Rheumatol, 2012
Pharmacologic Therapy of IIM
• • • • •
Corticosteroids Immunosuppressive Agents Combination regimens IVIg Biologic agents
Biologic Targets
• TNF – alpha
Anti-TNF-α Therapy in Myositis
• TNF-α and other proinflammatory cytokines are increased in muscle tissue of myositis patients [Lundberg, RDCNA, 2002] • TNF-α is toxic to myofibers and prevents their regeneration • TNF-α enhances other inflammatory cytokines in DM and PM
A Randomized, Pilot Study of Etanercept in Dermatomyositis
Anthony A. Amato, M.D.
Brigham and Women’s Hospital Harvard Medical School & THE MUSCLE STUDY GROUP Amato, Ann Neurol, 2011
Biologic Targets
• • TNF – alpha B cell
Rituximab in Myositis • • • • Open label study uncontrolled pilot trial in 7 adult refractory DM pts – Levine, Arth Rheum, 2005 Effective in antisynthetase syndrome – – Brulhart, Ann Rheum Dis, 2006 Sem, Rheumatol, 2009 Effective in refractory myositis and DM rash (some longstanding remission) – – Mok, J Rheumatol, 2007 Dinh, J Am Acad Derm, 2007 Ineffective for DM rash – Chung, Arch Dermatol, 2007
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
Participating Centers
Adult Sites
Alabama (Fessler) Boston (Narayanaswami) Cedars Sinai (Venuturupalli/Weisman) Czech Republic (Vencovsky) Dallas (Olsen)
Kansas City (Barohn/Latinis)
Kentucky (Crofford) London (Isenberg) Mayo Clinic (Ytterberg) Miami (Sharma) Michigan (Seibold/Schiopu) Michigan State (Martin/Eggebeen) Milwaukee (Cronin) New York: North Shore (Marder) New York: HSS (DiMartino) NIH (Miller) Philadelphia (Kolasinski) Phoenix (Levine) Pittsburgh (Oddis/Ascherman) Stanford (Chung/Fiorentino) Sweden (Lundberg)
Pediatric Sites
Boston (Kim) Cincinnati (Lovell) Duke (Rabinovich) Mayo Clinic (Reed) Miami (Rivas-Chacon) Michigan State (Martin/Eggebeen) NIH (Rider) Nova Scotia (Huber) Philadelphia (Sherry) Pittsburgh (Kietz) Stanford (Sandborg) Toronto (Feldman)
RIM Trial Summary
• Primary and secondary endpoints were not achieved •
83%
of refractory adult and juvenile myositis patients met the Definition of Improvement in this trial • There was a significant corticosteroid sparing effect noted in this trial between the baseline dose and the dose at study conclusion • Rituximab was generally well tolerated
Biologic Targets
• • • TNF – alpha B cell Other – Interleukin – 6 – Type 1 IFN
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 • IL-6 blockade is potential new approach to treatment of myositis • Anti-IL-6 effective/approved for RA Okiyama, Arth Rheum, 2009
Microarrays of DM and Normal Muscle • Cluster of genes known to be induced by IFN α/β – DM: genes were highly over-expressed compared to controls Greenberg, Ann Neurol, 2005 Gene expression: Red: high; black: intermed; green: low
DM patients
Type I IFN Gene Expression in DM • Results essentially duplicated with blood IFN signature correlating with disease activity • Also, multiplex ELISAs demonstrate increased levels of IFN-regulated chemokines that also correlated with disease activity IP-10, MCP-1, MCP-2
IFN signature, IFN-related cytokines both correlated with disease activity
Baechler, Mol Med, 2007
Type I IFN Genes, Chemokines and IL-6 in DM • Blood IFN gene expression, ELISA-based IFN-regulated chemokines and IL-6 in adult DM and JDM (n=56 pts) Bilgic, Arth Rheum, 2009
Type I IFN Genes, Chemokines and IL-6 in DM • Blood IFN gene expression, ELISA-based IFN-regulated chemokines and IL-6 in adult DM and JDM (n=56 pts) • Elevated levels of IL-6 and type I IFN –regulated transcripts and proteins in blood of adult DM and JDM Bilgic, Arth Rheum, 2009
Type I IFN Genes, Chemokines and IL-6 in DM • Blood IFN gene expression, ELISA-based IFN-regulated chemokines and IL-6 in adult DM and JDM (n=56 pts) • Elevated levels of IL-6 and type I IFN –regulated transcripts and proteins in blood of adult DM and JDM • IFN gene/protein signatures and serum IL-6 levels correlated with DM disease activity and with each other Bilgic, Arth Rheum, 2009
Type I IFN Genes, Chemokines and IL-6 in DM • Blood IFN gene expression, ELISA-based IFN-regulated chemokines and IL-6 in adult DM and JDM (n=56 pts) • Elevated levels of IL-6 and type I IFN –regulated transcripts and proteins in blood of adult DM and JDM • IFN gene/protein signatures and serum IL-6 levels correlated with DM disease activity and with each other • Suggests that coordinated dysregulation of type I IFN signaling and IL-6 production may contribute to DM pathogenesis Bilgic, Arth Rheum, 2009
Summary
• Myositis is heterogeneous and autoAbs help in classification and treatment • Lung disease is a critical prognostic determinant • Exciting time for therapeutic intervention in myositis – Temper our enthusiasm with a respect for all of these novel agents and their short and long term side effects
RIM Study: Trial Design
“Randomized Placebo Phase” Screen Rtx Early Rtx Late Wks 0/1 Rituximab Placebo Wks 8/9 Placebo Rituximab Weeks 12 – 44 Monthly Assessments • 200 myositis patients: 76 adult polymyositis (PM), 76 adult dermatomyositis (DM) and 48 Juvenile dermatomyositis (JDM) patients • Subjects randomly assigned, double-blind, to ‘Rtx Early’ or ‘Rtx Late’ • Patients were followed for 44 weeks • Myositis Core Set Measures (CSM) were assessed monthly Oddis, Arthritis Rheum, 2013
Primary Endpoint and Hypothesis • Primary Endpoint: Compare the time to DOI between the ‘Rtx Early’ and ‘Rtx Late’ groups • Hypothesis: The time to DOI will be statistically less (shorter) in early vs. late treatment groups
B cell Numbers Before and After Rituximab Early Rtx Late Rtx
Primary Outcome: Entire Cohort
Median time to DOI: Early Rtx = 20.0 weeks Late Rtx = 20.2 weeks p = 0.74 (log rank)
Primary Outcome: JDM
Median time to DOI: Early Rtx = 11.7 weeks Late Rtx = 19.6 weeks p = 0.32 (log rank)
100% 80% 60% 40% 20% 0%
Patients Meeting DOI During Trial
Early Rtx Late Rtx 80% 85% Overall, 83% (161/195) of subjects met the DOI during the course of the 44-week clinical trial
Corticosteroid Sparing Effect
25 20 15 10 5 0
21 p < 0.001
13.8
wk 0 wk 44 Timepoint There was a significant difference in the mean corticosteroid dose at baseline compared to the final visit
Kaplan Meier: Myositis Autoantibody Subsets MAA = myositis associated antibody
Future Directions: Anti-Jo-1 as Biomarker
Jo-1 levels decreased after rituximab and strongly correlated with disease activity
Rho = - 0.68
600 500 400 300 200 100 0 8 16 24 32 40
Weeks from rituximab
Median Rho = 0.68
95 90 85 80 75 300 400 500 600
Median Jo1
700 Abstract #750, ACR 2012