New insights in the management of SLE & APS. FOR GPs, internists, rheumatologists to simply diagnose & follow up your patients.

1. What’s new in SLE &
APS?
• Dr. Khuloud Saleh
• MD,FRCPC
• CONSULTANT RHEUMATOLOGY

2. Agenda
2019 EULAR/ACR new Lupus Classification
Criteria
EULAR 2019 non-renal Lupus management
Updates in Lupus nephritis management
(KDIGO 2021)
2019 EULAR /ACR Management for thrombosis
in APS
2022 ACR New classification criteria for APS

3. Systemic lupus
erythematosus (SLE)
• SLE is a systemic autoimmune disease with
multisystem involvement
• It is associated with significant morbidity and
mortality
• There are recent evolutions on diagnosis and
management of lupus in last couple years

5. Evolution of SLE Classification criteria

6. Evolution of SLE Classification criteria
1997
ACR 1997 criteria
2012
SLICC 2012 criteria
2019
EULAR/ACR 2019 criteria

9. ACR 1997 SLICC 2012 NEW CRITERIA
2019
Derivation
Sensitivity % 85 97 98
Specificity % 95 90 96
Validation
Sensitivity % 83 97 96
Specificity % 93 84 93

10. ACR 1997 SLICC 2012 NEW CRITERIA
2019
Derivation
Sensitivity % 85 97 98
Specificity % 95 90 96
Validation
Sensitivity % 83 97 96
Specificity % 93 84 93

13. Figure.
Antonis Fanouriakis et al. Ann Rheum Dis 2019;78:774
ANIF

15. Lupus nephritis
• Lupus nephritis (LN) is associated with increased morbidity and
mortality
• Renal biopsy is essential and the gold standard to diagnose LN
• Extra-glomerular involvement is seen in up to 60% of patients with
LN and is associated with poor outcomes
.
2020 Jun 4;22(7):30. doi: 10.1007/s11926-020-00906-7.

16. Lupus Nephritis subtypes
(LN)
• Class I: 1% Minimal change
• Class II: 10% Mesangial proliferative
• Class III: 20% Focal proliferative
• Class IV: 37% Diffuse proliferative
• Class V: 29% Membranous
• Class VI: 3% Advanced sclerosis

17. 2019 EULAR/ERA/EDTD Recommendations for management of LN
Recommendation

18. • Belimumab Approved in late December 2020, the U.S. Food & drug
administration (FDA) approved belimumab (Benlysta) to treat adults with active
lupus nephritis who are receiving standard therapy.
• An unmet need for lupus nephritis patients and is the result of an FDA
breakthrough therapy designation and priority review of findings from the
BLISS-LN study.
*N Engl J Med. 2020 Sep 17;383(12):1117–1128.

19. • Voclosporin, a novel calcineurin inhibitor, was approved in
combination with immunosuppressive therapy to treat adults with
active lupus nephritis by the FDA in January/2021.

20. Volume 100 issue 45 October
2021

21. Kidney biopsy
• The diagnosis of lupus nephritis ideally confirmed by a kidney biopsy
• Indications for kidney biopsy in SLE patients:
1) Urine protein > 500mg/day.
2) Rising serum creatinine/ decrease GFR that is not clearly attributable to
another mechanism
3) Hematuria(any level proteinuria) / active sediment

22. EULAR research agenda
• It is recommended that patients with SLE, including
those with lupus nephritis, be treated with
hydroxychloroquine or an equivalent anti-malarial
unless contraindicated,
• Lowers flares, including kidney
• Higher response rate to therapy
• Lower incidence of CV and thrombotic events in patients
with APS
• Less organ damage, improved lipid profile and better
preservation of bone mass
October 6, 2021

23. Lupus Science & Medicine 2019;6:e000310.doi:10.1136/lupus-2018-000310
Prevent disease flares
Protects from infections
Prevents autoimmune neonatal
heart
block
Correction of lipid
abnormalities
Prevention of metabolic
syndrome
Halting of
damage accrual

24. General management: Adjunctive treatment

25. CLASS I OR II LN TREATMENT

26. Class III and IV LN: induction therapy

27. Class III and IV LN: induction therapy

28. CLASS III AND IV LN: THERAPY

29. Class III and IV LN: maintenance therapy
• Glucocorticoids should be tapered to the lowest possible dose during
maintenance, except when glucocorticoids are required for extra-renal lupus
manifestations.
• Discontinuation can be considered after patients have maintained a complete
clinical response for ≥ 12 months.
• The total duration of immunosuppression plus combination maintenance
immunosuppression for proliferative LN should not be < 36 months.

30. Class V LN treatment

31. Class VI / ESRD
Hemodialysis, peritoneal
dialysis or kidney
transplantation (kidney
transplantation is preferred
to long term dialysis)
Transplantation can be
carried out as soon as
disease in remission

32. Assessing treatment response

33. Treatment of refractory LN

34. Anti-Phospholipid Syndrome (APS)

35. Agenda
• New ACR 2022 APS Classification criteria
• Is there a role for primary prophylaxis?
• Is there a role for DOAC in APS?
• CAPS treatment
• Management of APS in pregnancy

36. Definite APS: 1 Clinical + 1 Lab criteria
Clinical criteria
Vascular thrombosis-arterial or
venous
Pregnancy morbidity:
• 1 or more death of normal fetus at ≥
10WK
• 1 or more premature birth at ≤ 34
weeks due to severe preeclampsia or
placental insufficiency
• ≥ 3 consecutive abortions at < 10
weeks with other causes being rules
out
Laboratory criteria
• Anti-cardiolipin IgG and IgM
• Lupus anticoagulant (LAC)
• Antiß2-glycoprotein IgG and IgM
Medium – high titer (40 GPL or MPL or
higher than 99th percentile) at least 12
weeks from the clinical manifestation
2019 Revised SAPPORO classification criteria for APS

37. • Hematological features:
• Thrombocytopenia
• Hemolytic anemia
• Renal
• Acute thrombotic
microangiopathy
• Chronic vaso-occlusive lesions
• Cardiac
• Valvular heart disease
• Neurological features
• Dermatologic
• Livedo reticularis
• Livedoid vasculopathy
• Neurological features
• Cognitive dysfunction
• White matter lesions
Major APS features not included in the criteria
Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018 May 24;378(21):2010-2021.
Chaturvedi S, McCrae KR. Diagnosis and management of the antiphospholipid syndrome. Blood Rev. 2017 Nov;31(6):406-417.

38. • Sneddon's syndrome
• Pulmonary hypertension
• Splenic artery hemorrhage
• Addison's syndrome(adrenal
hemorrhage)
• Chorea
• Transverse myelopathy
• ARDS
• Renal thrombotic
microangiopathy,
• Budd-chiari syndrome
• Nodular regenerative
hyperplasia of the liver
• Avascular necrosis of the bone
• Cutaneous necrosis or
subungual splinter
hemorrhages
• Intracardiac thrombus
Rare APS manifestations

40. • aPL without clinical criteria for APS
• No strong evidence to support the use of Low Dose Aspirin
(LDA) EXCEPT:
• Cardiovascular risk factors
• SLE
• High risk aPL profile
Is there a role for primary prophylaxis in aPL?

41. EULAR Definitions of medium-high antiphospholipid
antibody (aPL) titres, and of high-risk and low-risk APL
profile

42. • ASA (80-100mg/day)
• ASA allergy : LMWH
• General measures: Avoid smoking and sedentary life, control HTN and
dyslipidemia
• Other drugs: hydroxychloroquine, statins and folic acid
Primary prophylaxis
(high risk)

43. Secondary thrombosis prevention in APS
Standard-intensity anticoagulation with warfarin for life long
INR 2-3

44. Patients who developed a thrombotic event while INR is therapeutic
(failure) :
1. Switch to LMWH
2. Oral anti coagulation + ASA or hydroxychloroquine
3. Increase the target INR 3.1-4
4. DOAC??
Treatment of Recurrent thrombosis
in spite of a therapeutic INR in patients with APS

45. Can the Direct Oral
Anti-coagulant
(DOIC) be used in
APS?
Can Direct Oral Anti-coagulant
(DOIC) be used in APS?

46. NO…
§ Trial of rivaroxaban in antiphospholipid syndrome (TRAPS)
§ Apixaban for the secondary prevention of thromboembolism among
patients with the antiphospholipid syndrome (ASTRO-APS)
§ Rivaroxaban for antiphospholipid antibody syndrome (RAPS)
No, especially in high risk patients ( triple positive aPL, arterial thrombosis,
recurrent events)
Trials of DOIC in APS?

48. Catastrophic Antiphospholipid Syndrome (CAPS)
A rare variant of APS (1%)
Systemic inflammatory response
syndrome (SIRS)
Characterized by thrombosis in
multiple organs and a Cytokine storm

49. CAPS

50. •Multiple simultaneous or evolving thrombotic events involving
microvasculature in < 1 week
•Malignant HTN (renal)
•ARDS (rapidly progressive pulmonary micro thrombosis, DAH)
•DIC
•Microangiopathic hemolytic anemia
•Thrombocytopenia
• Can be presenting manifestation of APS
Catastrophic Antiphospholipid Syndrome
signs and symptoms

51. CAPS criteria
• Definite (all 4)
• probable (all 4 with 2 organs involved, all but not 4 ( without 6 week
confirmation), or 1/2/4, 1/3/4 within 1 month despite anticoagulation)

52. • Early diagnosis and management are recommended.
• Based on the recently published clinical practice guidelines for CAPS
management:
• Combination therapy with :
• Glucocorticoids
• Heparin
• Plasma exchange or IVIG is recommended
• Concurrent treatment of precipitating factors is also recommended
• For refractory CAPS, B cell depletion (eg, Rituximab) or C5 inhibition (eg,
Eculizumab) therapies may be considered based on data from case reports.
Catastrophic antiphospholipid syndrome (CAPS)

53. • ASA 81 to 100mg daily before conception
• Once conception, add either heparin or LMWH until 34 weeks
• Resume LMWH at prophylactic dose one week post-partum for
6-12 weeks
Treatment of Pregnancy with APS

55. • Hydroxychloroquine
• Low dose ASA
• LDS (steroids 10-20mg)
• IVIG
• PLEX
• Anti-TNF (certolizumab/Adalimumab)
• Rituximab
Treatment of refractory pregnancy losses in APS patients

56. • Hydroxychloroquine+
• Low dose ASA +
• Anti-TNF *
*Jauume ALIJOTAS-Registry rt al.Semin Arthritis Rheum. 2019 Oct
Treatment of refractory pregnancy losses in APS patients

57. Thanks for listening
Questions?