חוברת מדדים בראומטולוגיה זה בידיים שלכם! Assessment of Disease Activity in Rheumatology
האיגודים האמריקני והאירופי קבעו מדדים לאבחון רוב מחלות המפרקים. כאשר בעבודה השגרתית הכלי העיקרי לאבחנה הוא שילוב נתונים קליניים, בדיקות מעבדה, בדיקות הדמייה ומדדי אבחון. עולם המדדים בראומטולוגיה עצום, חמושים בחזון המשותף של העלאת הסטנדרט הטיפולי וקירוב מטופלים ליעדי הטיפול. .ABBVIE אנו גאים להציג בפניכם שיתוף פעולה יחודי בין האיגוד הראומטולוגי לבין חברת .SLE ו- EA,BSA,AS יחד, יצרנו חוברת מדדים פרקטית ושימושית שמרכזת את מדדי המחלות חוברת מקיפה זו היא שער נוסף למידע מקצועי ונגיש מעולם הראומטולגיה . אנו מבינים את האתגרים שעומדים באיסוף המידע במקור אחד, לכן אצרנו בקפידה את המשאב הזה כדי לרכז עבורכם את הכלים החיוניים לעבודתכם מתוך מטרה קולקטיבית לשפר את הסטנדרט הטיפולי ולהתאים תוכניות טיפול בהתאם לצרכיו הייחודיים של כל מטופל. מקווים שחוברת הזו תרכז עבורכם את המידע העדכני והרלוונטי מעולם המדדים. וביחד, נמשיך להשפיע משמעותית על חייהם של אינספור חולים הנאבקים במחלות ראומטולוגיות, נעצב מחדש את נוף הראומטולוגיה ונשנה חיים. Rheumatoid arthritis (RA) Psoriatic arthritis (PsA) Axial Spondylarthritis (AS) Systemic Lupus Erythematosus (SLE) Systemic Sclerosis (SSc) Infammatory muscle disease Appendix :הקדמה Index 2 11 20 27 32 35 36 1
Rheumatoid arthritis (RA) Assessment of Disease Activity Structured assessment of disease activity in RA has facilitated a standardized quantitative assessment of disease activity, the response to therapy, and achievement of therapeutic goals (treat-to-target strategy). Structured assessments of disease activity and of functional status are important parts of the monitoring of patients with RA. Key individual variables Swollen and tender joint counts Patient assessment of pain Patient global assessment (PGA) of disease activity Physician global assessment (PhGA) of disease activity Acute phase response measures Core sets of clinical and laboratory variables for the assessment of disease activity in patients with RA have been used in different combinations and relative weights to create the composite disease activity measures used in clinical practice and research. 28 joint count has become a standard for use in both clinical practice and clinical trials. * 28 joint count excludes assessments of the foot and ankle joints. Swollen and tender joint counts (SJC and TJC) 2
Physician (evaluator) global assessment (PhGA or EGA) PhGA/EGA is assessed in a similar manner to pain using visual analog scale or numerical rating scales; typically integrates information from both subjective and objective variables. Acute phase response measures Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) are the two biomarkers used most widely to assess disease activity, correlating well with both clinical disease activity measurements and radiographic progression of joint damage. Patient assessment of pain (patient-reported outcome) Pain is measured by visual analog scales, which most often use horizontal 100 mm lines. Patients indicate their degree of pain (typically over the preceding week) by placing a mark between "no pain" (left end, 0 mm) and worse possible pain (right end, 100 mm). Alternatives to visual analog scales include numerical rating scales (ranging from 0 to 10). Visual Analogue Scale (VAS) No pain severe intolerable pain 0 100 Patient global assessment (PGA) of disease activity (patient-reported outcome) PGA is assessed in a similar manner to pain using visual analog scale or numerical rating scales. ell oor W r Very P y Ve 10cm ll r e ooPry Very W Ve 0 10cm 0 3
Composite indices for disease activity assessment Structured composite measures are used to facilitate regular monitoring of disease activity in clinical practice and to assess disease activity in clinical trials. Simplifed Disease Activity Index (SDAI) = a linear sum of unweighted, untransformed variables: SJC28 + TJC28 + PGA (0-10) + EGA (0-10) + CRP level (mg/dl) Disease activity measures preferred by the EULAR and ACR for clinical practice use: Clinical Disease Activity Index (CDAI) Simplifed Disease Activity Index (SDAI) Disease Activity Score using 28 joints (DAS28) DAS28-ESR/CRP Routine Assessment of Patient Index Data 3 (RAPID3) PRO based indices Patient Activity Scale (PAS) II All of the measures accurately refect disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity; have remission criteria; and are feasible to perform in clinical settings.* Ref: * Anderson J. Arthritis Care Res (Hoboken) 2012; 64:640. England BR. Arthritis Care Res (Hoboken) 2019; 71:1540 Clinical Disease Activity Index (CDAI) = a linear sum of unweighted, untransformed variables: SJC28 + TJC28 + PGA (0-10) + EGA (0-10) CDAI Score Range Disease Severity ≤ 2.8 Remission > 2.8 - 10.0 Low > 10.0 - 22.0 Moderate > 22.0 High Ref: Aletaha D Arthritis Res Ther. 2005; 7(4): R796–R806; Aletaha D. Res Clin Rheumatol. 2007 Aug;21(4):663-75 Ref: Smolen J. Rheumatology 2003;42:244–257; Aletaha D. Res Clin Rheumatol. 2007 Aug;21(4):663-75. SDAI Disease Severity ≤3.3 Remission >3.3-11.0 Low >11.0-26.0 Moderate >26.0 High 4
Disease Activity Score using 28 joints DAS28-ESR/CRP DAS28 which utilizes a 28 joint count provides a global summative and continuous score for disease activity assessment and has been widely used in practice and in clinical trials. The DAS28 can be calculated using either the ESR or CRP. DAS28-ESR = (0.56*√(Tender Joint Count)+0.28*√(Swollen Joint Count)+0.7*ln(ESR)+0.014*(global health)) DAS28-CRP = (0.56*√(tender joint count) + 0.28*√(swollen joint count) + 0.36*ln(CRP, mg/L + 1) + 0.014*patient global + 0.96) < 2.6 Remission ≥ 2.6 - < 3.2 Low ≥ 3.2 - ≤ 5.1 Moderate > 5.1 High Routine Assessment of Patient Index Data 3 (RAPID3) The RAPID3 constitutes an index that is based upon patient self-reported outcomes only and is simple for the patient to complete. It includes the Health Assessment Questionnaire (HAQ), physical function, pain, and PGA, all normalized to 0 to 10, counted together, and divided by 3 to yield a score on a scale of 0 to 10. Other comorbidities, such as OA and fbromyalgia, may infate the score apart from RA disease activity and confound its interpretation. ≤3 Remission 3.1-6 Low 6.1 - 12 Moderate > 12 High Ref: Prevoo ML, Arthritis and Rheumatism 1995, 38 (1): 44-8. Daniel Aletaha. Arthritis and Rheumatism 2005, 52 (9): 2625-3 DAS28 Score Range Disease Severity < 2.6 Remission ≥ 2.6 - < 3.2 Low ≥ 3.2 - ≤ 5.1 Moderate > 5.1 High DAS28 Score Range Disease Severity RAPID3 scores Disease Severity 5
1. Please check (√) the one best answer for your abilities at this time: With With UNABLE OVER THE LAST WEEK, were you able to: SOME MUCH To Do Diffculty Diffculty a. Dress yourself, including tying shoelaces and doing buttons? 1 2 3 b. Get in and out of bed? 1 2 3 c. Lift a full cup or glass to your mouth? 1 2 3 d. Walk outdoors on fat ground? 1 2 3 e. Wash and dry your entire body? 1 2 3 f. Bend down to pick up clothing from the foor? 1 2 3 g. Turn regular faucets on and off? 1 2 3 h. Get in and out of a car, bus, train, or airplane? 1 2 3 i. Walk two miles or three kilometers, if you wish? 1 2 3 j. Participate in recreational activities and sports as you would like, 1 2 3 if you wish? k. Get a good night’s sleep? 1.1 2.2 3.3 l. Deal with feelings of anxiety or being nervous? 1.1 2.2 3.3 m. Deal with feelings of depression or feeling blue? 1.1 2.2 3.3 2. How much pain have you had because of your condition OVER THE PAST WEEK? please indicate below how severe your pain has been: NO PAIN AS BAD AS PAIN 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 IT COULD BE 3. Please place a check (√) in the appropriate spot to indicate the amount of pain you are having today in each of the joint areas listed below: a. LEFT FINGERS i. RIGHT FINGERS b. LEFT WRIST j. RIGHT WRIST c. LEFT ELBOW k. RIGHT ELBOW d. LEFT SHOULDER l. RIGHT SHOULDER e. LEFT HIP m. RIGHT HIP f. LEFT KNEE n. RIGHT KNEE g. LEFT ANKLE o. RIGHT ANKLE h. LEFT TOES p. RIGHT TOES q. NECK r. BACK 4. Considering all the ways in which illness and health conditions may afect you at this time, please indicate below how you are doing: VERY VERY WELL 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 POORLY Without ANY Diffculty 0 0 0 0 0 0 0 0 0 0 0 0 0 None 0 0 0 0 0 0 0 0 0 None 0 0 0 0 0 0 0 0 0 Mild 1 1 1 1 1 1 1 1 1 Mild 1 1 1 1 1 1 1 1 1 Moderate 2 2 2 2 2 2 2 2 2 Moderate 2 2 2 2 2 2 2 2 2 Severe 3 3 3 3 3 3 3 3 3 Severe 3 3 3 3 3 3 3 3 3 Ref: Pincus T. The Journal of Rheumatology 2008; 35:11 6
Patient Activity Scale - II (PAS-II) The PAS II is a composite index composed of a visual analog scale for pain, scored from 0 to 10; a PGA, expressed on a visual analog scale from 0 to 10; and the HAQ-II We are interested in learning how your illness affects your ability to function in daily life. Place an X in the box which best describes your usual abilities OVER THE PAST WEEK: Stand up from a straight chair? Walk outdoors on fat ground? Get on/off toilet? Reach and get down a 5 pound object (such as a bag of sugar) from just above your head? Open car doors? Do outside work (such as yard work)? Wait in a line for 15 minutes? Lift heavy objects? Move heavy objects? Go up two or more fights of stairs? We are also interested in learning whether or not you are afected by pain because of your illness. How much pain have you had because of your illness in the past week? Place an X in the box that best describes the severity of your pain on a scale of 0-10 NO SEVERE PAIN PAIN Considering ALL THE WAYS THAT YOUR ILLNESS AFFECTS YOU, RATE HOW YOU ARE DOING on the following scale. Place an X in the box below that best describes how you are doing on a scale of 0-10 VERY VERY WELL POOR Without Any With With Unablt To Do Diffculty Soce 4uch Diffculty Diffculty (0) (1) (2) (3) Are you able to: 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 Ref: Wolfe F. J Rheumatol. 2005 Dec;32(12):2410-5. 7
Assessment of physical function Physical function is a central aspect of life for patients with RA and thus a major focus of patient care. In clinical practice, function is most commonly evaluated with questionnaires, typically the Health Assessment Questionnaire (HAQ). ACR-preferred measures for assessment of physical function for routine clinical use HAQ-II • a simplifed HAQ:10 questions with 4 levels of diffculty each. Multidimensional HAQ (MD-HAQ) • The forms for the HAQ, the HAQ-II, and the MD-HAQ can be obtained from online sources, such as rheuminfo.com/physician-tools/health-assessment-questionnaires-haq-haq-ii-mdhaq/ Physical Function 10-item Short Form (Patient-Reported Outcomes Measurement Information System Physical Function 10-item Short Form [PROMIS PF10a]) • a short patient questionnaire of 10 questions related to physical function that are categorized into 5 states of diffculty. https://www.healthmeasures.net/explore-measurement-systems/promis Assessment of fatigue Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F) • a brief (13 items) measure for assessment of self-reported fatigue and its impact upon daily activities and function.Scores range from 0 to 52, with higher scores refecting less fatigue. • FACIT-F has been validated for use in patients with RA; can be applied also in patients with other rheumatic diseases. 1 • FACIT website: http://www.facit.org/ Ref: 1. Cella D. J Rheumatol. 2005;32:811-9. Singh H. J Clin Rheumatol. 2014;20(2):87-90. Elera-Fitzcarrald C. Arthritis Care and Research, 2020;72, S10:369–409. Response Criteria Response criteria are mainly used for clinical trials and less frequently in daily practice. ACR response criteria ACR response criteria were developed to best discriminate the effects of active drug from placebo in clinical trials.* ACR response is scored as a percentage of improvement, comparing disease activity at two discrete time points (usually baseline and post-baseline comparison). The ACR response criteria is a dichotomous variable with a positive (=responder) or negative (=non-responder) outcome. The ACR20 response has been the preferred endpoint for clinical trials because it discriminates optimally between active treatment and placebo.** * Felson DT. Arthritis Rheum. 1995;38:727–35. ** Felson DT, Arthritis Rheum. 1998;41:1564–70 8
EULAR response criteria are based upon the DAS or DAS28, categorizing improvement into either good or moderate responses. These criteria require not only a certain degree of improvement but also attainment of a good (or moderate) disease activity state. CDAI and SDAI response criteria CDAI and SDAI are continuous scores for which validated response criteria exist that are useful in clinical practice. Response cutoffs have been defned for the CDAI and SDAI that correspond with the traditional ACR responses; these defnitions of minor, moderate, and major response have been defned as relative improvements of SDAI or CDAI of 50, 70, or 85 percent, respectively. Remission criteria Remission is the ultimate treatment goal for RA treatment. Remission is regarded as no or only minimal residual disease activity. ACR and EULAR provisional defnition of remission defnition ACR and EULAR provisional defnition of remission for clinical trials and for clinical practice are stringent and do not allow residual disease activity beyond a minimal extent of residual joint swelling or tenderness. They are either index based on the SDAI (<=3.3) or Boolean based (i.e., an “intersection” of several criteria) that include the fulfllment of the following four conditions: a maximum of 1 swollen joint + a maximum of 1 tender joint + a maximum of 1 cm patient global assessment (0- to 10-cm scale) + a maximum of 1mg/dl of CRP. For clinical practice, clinical remission criteria correspond to the CDAI (≤2.8) and the Boolean without the CRP requirement (i.e., needing 3/3). ACR Response Criteria ACR20 / ACR50 / ACR70 • ≥ 20%/50%/70% improvement in: - Swollen joint count - Tender joint count - Improvement in at least 3 of the following 5 measures: • Patient's global assessment of disease activity • Physicians' global assessment of disease activity • Patient's assessment of pain • Acute-phase reactant (ESR, CRP) • Disability (HAQ) EULAR response criteria DAS28 at (mprovtmtnt in DAS or DAS28 from Bastlint Endpoint > 1.2 > 0.6 and ≤ 1.2 ≤0.6 ≤ 3.2 Good >3.2 and ≤ 5.1 Moderate >5.1 None Ref: van Gestel AM. Arthritis Rheum 1996; 39:34. van Gestel AM. Arthritis Rheum 1998; 41:1845. Smolen J. Rheumatology 2003;42:244–257; Aletaha D. Res Clin Rheumatol. 2007 Aug;21(4):663-75. Ref: Aletaha D. Ann Rheum Dis 2012; 71:1190. 9
ACR-EULAR 2011 Defnition of Remission RA disease activity states defned by EULAR 2019 Disease activity states Remission ACR-EULAR remission defnition (Boolean or index based) Low disease activity state according to any of the validated composite Low disease activity disease activity measures that include joint counts Respective disease activity state according to any of the validated Moderate, high disease activity composite disease activity measures that include joint counts For clinical trials For clinical practice • Boolean • Boolean - SJC, TJC, PtGA, CRP all ≤1 - SJC, TJC, PtGA all ≤1 • Index-based • Index-based - SDAI ≤3.3 - CDAI ≤2.8 - SDAI=SJC+TJC+PhGA+PtGA+ CRP (mg/dl) - CDAI=SJC+TJC+PhGA+PtGA Ref: Felson D. Ann Rheum Dis 2011;70;404-13. Ref: Smolen J. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. 10.1136/annrheumdis-2019-216655 10
Psoriatic arthritis (PsA) - Assessment of Disease Activity PsA is a multifaceted heterogeneous disease, involving the following domains: joints, entheses, dactylitis, axial skeleton, and skin & nails. The treatment target is considered clinical remission or, alternatively, low disease activity. Validated measures of musculoskeletal and skin disease activity should be used in clinical practice to guide treatment decisions. ref: Gossec L, Baraliakos X, Kerschbaumer A, et al. Ann Rheum Dis 2020;79:700–712. Singh JA et al. Arthritis Rheumatol. 2019 Jan;71(1):5-32. To date, there is no consensus on the disease activity indices for use in clinical practice and on the defnition of remission in PsA. Domains-based disease assessment Articular disease: 66 swollen and 68 tender joint counts (SJC and TJC) Swollen Tender Swollen Tender Joints Joints Joints Joints Temporomandibular joint (0-2) (0-2) Sternoclavicular joints (0-2) (0-2) Acromioclavicular joints (0-2) (0-2) Glenohumeral(s) (0-2) (0-2) Elbow(s) (0-2) (0-2) Wrist(s) (0-2) (0-2) Metacarpal phalangeal joints (0-10) (0-10) Finger Proximal interphalangeal joints (0-10) (0-10) Finger Distal interphalangeal joints (0-8) (0-8) Hip(s) NA (0-2) Knee(s) (0-2) (0-2) Ankle(s) (0-2) (0-2) Tarsus/Midfoot(feet) (0-2) (0-2) Metatarsal phalangeal joints (0-10) (0-10) Toe PIP(s) (0-10) (0-10) Total joint counts (0-66) (0-68) Ref: Duarte-García A et al. J Rheumatol 2019;46:996–1005. 11
Non-articular musculoskeletal disease Enthesitis: LEI was developed as a measure for enthesitis in PsA. LEI evaluates 6 entheseal sites for presence or absence of tenderness when putting pressure (4Kg - enough to blanch the nail of the examiner): • bilateral lateral epicondyles • medial femoral condyles • Achilles tendon insertions Overall score range of 0–6. Higher count represents greater enthesitis burden. ref: Healy PJ, Helliwell PS. Arthritis Rheum 2008;59:686–91. Mease PJ. Arthritis Care Res 2011;63(S11):S64–S85. Leeds enthesitis index (LEI) Leed Enthesis Index - Lateral epicondyle (L,R) Leed Enthesis Index Medial femoral condyle (L,R) Leed Enthesis Index Achilles tendon insertion (L,R) 12
Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis measure SPARCC was developed as a measure for enthesitis in spondyloarthritis in general. SPARCC evaluates 16 entheseal sites for presence or absence of tenderness: • supraspinatus insertion into the greater tuberosity of the humerus • medial and lateral epicondyles • patellar tendon insertion at the base of the patella • quadriceps insertion into the superior border of the patella - the inferior patella and tibial tuberosity are considered 1 site because of their anatomical proximity for scoring purposes • bilateral Achilles tendons • plantar fascia insertion at the calcaneus Overall score 0–16. Higher score represents greater enthesitis burden. * In view of high general sensitivity to touch in patients with fbromyalgia, clinical evaluation of enthesopathy is not reliable in patients with fbromyalgia. Spondyloarthritis Research Consortium Canada Enthesitis Index (0-16) Supraspinosus insertion (L,R); Medial epicondyle (L,R); Lateral epicondyle (L,R); Greater trochanter (L,R); Quadriceps patellar insertion (L,R); Patellar ligament insertion or Tibial tubercle (L,R); Insertion of Achilles tendon (L,R); Plantar fascia insertion (L,R); ref: Maksymowych WP, Mallon C, Morrow S, et al. Ann Rheum Dis. 2009;68(6):948–953. Greater trochanter (L,R) Supraspinatus insertion (L,R) Medial epicondyle (L,R) Lateral epicondyle (L,R) Plantar fascia insertion (L,R) Quadriceps patellar insertion (L,R)Patellar ligament insertion or Tibial tubercle (L,R) Achilles tendon insertion (L,R) Greater trochanter 13
Dactylitis Dactylitis or fusiform swelling of an entire digit is a typical feature of PsA. A number of dactylitis measures are available: • Count of digits with dactylitis (tender and non-tender) • Count of tender dactylitic digits • Semi-quantitative measure: - 0–3 scale of physician-rated severity for affected digits (20 digits in total; maximum overall score of 60) • Leeds Dactylitis Index (LDI) - Objective determination of the presence of dactylitis - Requires dactylometer - a defnition of dactylitis = 10% difference in the ratio of circumference of the affected digit to the contralateral digit. - dactylitis severity is defned by tenderness score (graded 0–3) - LDI =ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot multiplied by a tenderness score (graded 0–3) - recommended by OMERACT for use in clinical trials Leeds Dacylitis Index Axial disease (Assessment of SpondyloArthritis International Society (ASAS) measures as discussed in axial spondyloarthropathy section) Circumference Circumference Final score Finger or Toe Tenderness score (C) involved digit (A) Contralateral digit(or Tables)(B) [{(A/B)-1}x100]xC TOTAL Ref: Helliwell P.S. et al. J Rheumatol 2005; 32:1745-1750. Kaeley GS et al. Semin Arthritis Rheum 2018;48:263–273 14
Skin Psoriasis area and severity index (PASI) PASI is the most widely used outcome for psoriasis in PsA studies, although it is less discriminative at low levels of skin disease. PASI is a quantitative rating score for measuring the severity of psoriatic lesions based on area coverage and plaque appearance • The head, upper extremities, lower extremities and trunk are assessed separately and then combined using weighting based on the surface area represented by each area • The degree of erythema, induration and scale in each area are judged on a 0–4 scale • The area of involvement of each area is graded from 0 to 6, depending on the estimated percentage of lesioned area • These body scores are multiplied by the disease severity score and the weighting for each body area, yielding a score between 0 and 72 Head Area 0% Erythema (redness) Induration (thickness) Desquamation (scaling) Arms Area Erythema (redness) Induration (thickness) Desquamation (scaling) Trunk Area Erythema (redness) Induration (thickness) Desquamation (scaling) Legs Area Erythema (redness) Induration (thickness) Desquamation (scaling) Mild disease PASI < 10 Moderate disease PASI 10-15 Severe disease PASI > 15 PASI calculator website: http://pasi.corti.li/ Ref: Fredriksson T, Pettersson U. Dermatologica 1978;157(4):238–44. Coates L. Rheum Dis Clin N Am 41 (2015) 699–710 0% 0% 0% 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 10% 10% 10% 10% 10-29% 10-29% 10-29% 10-29% 30-49% 30-49% 30-49% 30-49% 50-69% 50-69% 50-69% 50-69% 70-89% 70-89% 70-89% 70-89% 90-100% 90-100% 90-100% 90-100% 15
Body surface area (BSA) BSA is a commonly used measure of severity of skin disease defned as the percentage of the total body surface area affected by psoriasis. 1% BSA represents a one handprint size of the patient, and it ranges from 0% to 100%. Nail psoriasis Moderate psoriasis Severe psoriasis Less than 3% 3%-10% of the More than of the body has body has psoriasis 10% of the body * psoriasis has psoriasis Nail psoriasis severity index (NAPSI) The target nail is graded for nail matrix psoriasis (any of the following: pitting, leukonychia, red spots in the lunula, and nail plate crumbling) and nail bed psoriasis (any of the following: onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, and nail bed hyperkeratosis). The sum of these two scores is the total for that nail. Nail Matrix Psoriasis Score for Nail Matrix Psoriasis Indicated by: pitting, leukonychia, 0 = none red spoes in the lunula, or nail plate 1 = present in 1/4 nail crumbling 2 = present in 2/4 nail 3 = present in 3/4 nail 4 = present in 4/4 nail Ref: Rich P. J Am Acad Dermatol 2003;49;206–22 Nail Psoriasis: Diagnosis, Assessment, Treatment Options, and Unmet Clinical Needs, Gurjit S. Kaeley, Lihi Eder, Sibel Zehra Aydin, Phoebe Rich and Catherine J. Bakewell, The Journal of Rheumatology August 2021, 48 (8) 1208-1220; DOI: Images courtesy of Phoebe Rich, MD. Nail Bed Psoriasis Score for Nail Psoriasis Indicated by: presence/absence of: onycholysis, 0 = none splinter hemorrhages, oil drop, discoloration, or 1 = present in 1/4 nail nail bed hyperkeratosis 2 = present in 2/4 nail 3 = present in 3/4 nail 4 = present in 4/4 nail Total for Each Nail______ (0-8) * Coates L. Rheum Dis Clin N Am 41 (2015) 699–710. Pitting, leukonychia Leukonychia Red macules in lunula Crumbling Trachyonychia Splinter hemorrhages Hyperkeratosis and Salmon patch or oil Onycholysis and onycholysis splinter hemorrhages spot dyschromia and salmon patch dyschromia 16
≤ 4 Remission > 4 and ≤ 14 Low > 14 and ≤ 28 Moderate > 28 High Composite indices for disease activity assessment Disease Activity index for PSoriatic Arthritis (DAPSA) • a validated and easy to use measure for clinical and trial use in PsA • based on the summation of fve variables: SJ66+TJ68+PtGA (cm)+pain VAS (cm)+CRP (mg/dL) • DAPSA evaluates only peripheral joints and does not refect axial involvement. DAPSA (Disease Activity in Psoriatic Arthritis) Score Tender Joints Swollen Joints 1. Tender Joints Count (0-68), TJ: 2. Swollen Joints Count (0-66), SJ: 3. CRP (mg/dl): 4. Patient's assessment of disease activity and pain How active was your rheumatic disease on average during the last week? How would you describe the overall level of joint pain during the last week? DAPSA = TJ + SJ + CRP + ACTIVITY + PAIN = Disease Activity: 0-4 Remission, 5-14 low, 15-28 moderate, >28 high Disease Activity Ref: Eberl G. Rheumatology (Oxford) 2000;39:148–55. Schoels MM. et al. Ann Rheum Dis 2016;75:811–818 Not active Very active 012345678910 None Very severe 012345678910 DAS28 Score Range Disease Severity 17
Ref: Mumtaz A, Gallagher P, Kirby B, et al. Ann Rheum Dis 2011;70(2):272–7. * HAQ- Health Assessment Questionnaire - see appendix ** DLQI- DERMATOLOGY LIFE QUALITY INDEX - see appendix *** ASQoL- Ankylosing Spondylitis Quality of Life - see appendix Composite psoriatic disease activity index (CPDAI) - includes all domains of PsA (peripheral joints, skin, entheses, dactylitis, and axial disease) score range - 0 to 15. - mainly used in research/clinical trials None (0) Mild (1) Moderate (2) Severe (3) Peripheral ≤4 joints; ≤4 joints but function impaired; >4 joints arthritis normal function 0r >4 joints, normal function and function impaired (TJC/SJC) (HAQ<0.5)* Skin disease PASI ≤10 and PASI ≤10 but DLQI** >10; PASI >10 DLQI** ≤10 or PASI >10 but DLQI** ≤10 and DLQI** >10 ≤3 sites; ≤3 sites but function impaired; >3 sites Enthesitis normal function or >3 sites but normal function and function impaired (HAQ* <0.5) ≤3 digits; ≤3 digits but function impaired; >3 digits Dactylitis normal function or >3 digits but normal function and function impaired (HAQ* <0.5) BASDAI <4; BASDAI >4 but normal function; BASDAI >4 Spinal disease normal function BASDAI <4 but function impaired and function impaired (ASQoL*** <6) Modifed CPDAI - includes domains as in CPDAI, excluding spinal manifestations, scored using a 4-point scale from 0 (no disease activity) to 3 (most severe disease activity), score range of 0–12. - mainly used in research/clinical trials PsA Disease Activity Score (PASDAS) - a complicated composite measure including the following variables: - SJC, TJC, enthesitis (LEI), dactylitis count, physician and patient global assessments, CRP mg/l, SF-36 - provides disease activity states as well as response criteria - used in research/clinical trials Ref: Helliwell PS, FitzGerald O, Fransen J et al. Ann Rheum Dis 2013;72:986–91 Ref: Gladman D. J Rheumatol Suppl 2015;93:14–16. 18
Minimal disease activity (MDA) criteria The criteria state that a patient is in MDA if they fulfll 5 of 7 of the following criteria: • Tender joint count (TJC) ≤1 • Swollen joint count (SJC) ≤1 • PASI ≤1 or BSA ≤3 • Patient pain VAS ≤15 • PGA VAS ≤20 • HAQ ≤0.5 • Tender entheseal points ≤1 Very low disease activity (VLDA) defned as a patient meeting all seven of the above criteria. Ref: Coates LC, Fransen J, Helliwell PS. Ann Rheum Dis 2010;69(1): 48–53. Psoriatic arthritis response criteria (PsARC) • PsARC are used in the assessment and monitoring of PsA in clinical trials • PsARC consists of four components: 68 TJC, 66 SJC, patient and physician global disease assessment • PsARC requires improvement in two factors (with at least one being a joint score), with worsening in none, of the previous four factors Ref: Mease PJ, et al. Arthritis Rheum 2005;52:3279–89. Defnition of remission in PsA According to 2017 update of recommendations by an international task force, DAPSA or MDA should be considered to defne the target of treatment in PsA (Ref: Smolen JS, Schols M, Braun J, et al. Ann Rheum Dis 2018;77:3–17). This recommendation is supported by the 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis (ref: Singh JA https://doi.org/10.1002/acr.23789). 19
Axial Spondylarthritis - Assessment of Disease Activity Axial spondyloarthritis (SpA) includes ankylosing spondylitis (AS), radiographic axial spondyloarthritis, and nonradiographic axial spondyloarthritis. The treatment target for axial SpA is remission or low disease activity. Disease activity measures Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) The BASDAI is an instrument for the assessment of disease activity that is presented in a questionnaire format/patient-reported outcome measure. BASDAI is based on six questions (Q), each scored from 0 to 10. BASDAI score = (Q1 + Q2 + Q3 + Q4 + (Q5 + Q6)/2) / 5 The total BASDAI score ranges from 0 to 10 points. A BASDAI score of ≥4 (on a scale of 0 to 10) is indicative of active disease. BASDAI score is used in clinical practice and clinical trials. Please circle the number that most closely corresponds to your condition during the past week 1. How would you describe the overall level of fatigue/tiredness you have experienced? Not active Very severe 2. How would you describe the overall level of infammatory neck, back or hip pain you had? 3. How would you describe the overall level of pain/swelling in joints other than neck, back or hips you have had? 4. How would you describe the overall level of discomfort you have had from any areas tender to touch or pressure? 5. How would you describe the overall level of morning stiffness you have hade from the time you wake up? 6. How long does your morning stiffness last from the time you wake up? 012345678910 Normal Very severe 012345678910 Normal Very severe 012345678910 Normal Very severe 012345678910 Normal Very severe 012345678910 Normal Very severe 012345678910 0 hrs (=0) 1/2 hr (=2.5) 1 hr (=5) 1 1/2 hr (=7.5) 2 hrs (=10) 20
The Ankylosing Spondylitis Disease Activity Score (ASDAS) ASDAS is a composite index to assess disease activity in axial SpA. ASDAS combines fve disease activity variables with only partial overlap, resulting in one single score with better validity, enhanced discriminative capacity, and improved sensitivity to change as compared to single-item variables. 1. How would you describe the overall level of a neck, back or hip pain you have had? None Very severe How long does your morning stiffness last from the time you wake up? 3. How active was your spondylitis on average during the last week? 4. How would you describe the overall level of pain/swelling in joints other than neck, back or hips you have had? 5. C-reactive protein (mg/L)? The ASDAS categorizes the disease activity as inactive, low, high, or very high. According to the 2016 ASAS-EULAR management recommendations for axial spondyloarthritis, ASDAS is considered a preferred measure for the assessment of disease activity applied in the treat-to-target strategy. ASDAS ≥2.1 warrants consideration of biologic therapy. 012345678910 2 or more Hours 012345678910 None Very severe 012345678910 Not active Very active 012345678910 ASDAS <1.3 • Inactive disease 1.2≤ ASDAS <3.5 • High disease activity ASDAS >3.5 • Very high disease activity 1.3≤ ASDAS <2.1 • Moderate disease activity 21
Rheumatologist's diagnosis of axial SpA and Elevated CRP and/or positive MRI and/or Radiogaphic sacroilitis* and Failure of standard treatment: all patients • at least 2 NSAIDs over 4 weeks (in total) patients with predominant peripheral manifestations • one local steroid injection if appropriate • normally a therapeutic trial of sulfasalazine and High disease activity: ASDAS ≥ 2.1 or BASDAI ≥ 4 and Positive rheumatologist's opinion ASAS-EULAR recommendations for the treatment of patients with axSpA with bDMARDs. Ref: van der Heijde D, Ramiro S, Landewé R, et al. Ann Rheum Dis 2017;76:978–991. Smolen JS, Schols M, Braun J, et al. Ann Rheum Dis 2018;77:3–17. 2019 ACR/SPARTAN conditionally recommend against using a target of ASDAS over a treatment strategy based on physician assessment. This recommendation is based on a low level of evidence. Ref: Ward M et al. Arthritis & Rheumatology Vol. 71, No. 10, October 2019, pp 1599–1613. Assessment of spinal mobility Bath AS Metrology Index (BASMI) The BASMI is a composite index of spinal mobility, used in clinical practice and research to measure spinal mobility and is recommended by the ASAS. The BASMI is used to obtain a baseline measurement and monitor change over time and to assess the impact of clinical interventions. The scale of the BASMI ranges from 0 to 10, where 0 is no mobility limitation and 10 is very severe limitation. • tragus-to-wall distance (TWD) - The patient is standing with the heels and back resting against the wall, with the hips and knees as straight as possible. The chin should be held at the usual carrying level. The patient is asked to put maximal effort to touch the head against the wall. The distance between the tragus and wall is measured twice in cm to the nearest 0.1 cm on the left side, and the better of two tries is recorded. The same procedure is followed for the right side. The fnal TWD is calculated by averaging the best value for the left and the right side. • modifed Schober’s test - The patient is standing erect. An imaginary line, connecting both posterior superior iliac spines, is marked. A second mark is placed 10 cm above the frst mark. The patient is asked to bend forward maximally, and the distance between the two marks is measured. The increase in cm to the nearest 0.1 cm is recorded. The modifed Schober is measured twice, and the better of two tries is recorded. • cervical rotation - The patient is sitting straight on a chair, and the chin at the normal carrying level. The assessor places a goniometer at the top of the head in line with the nose. The patient is asked to rotate the neck maximally to the left, and the assessor follows with the goniometer. The angle between the frst sagittal plane and the new plane after rotation is measured in degrees. The better of two tries is recorded. The same procedure is followed for the right side. The fnal score for cervical rotation is calculated by averaging the best values for the left and the right side and recorded in degrees. 22
• lateral spinal fexion - The patient is standing with the heels and back resting against the wall, without fexion in the knees and without bending forward. A frst mark is placed on the right thigh, at the level of the patient’s middle fngertip. The patient is then asked to bend sideward to the right as far as possible without bending the knees or lifting the heels, and a second mark is placed again at the level of the patient’s middle fngertip. The distance between the two marks is measured in cm to the nearest 0.1 cm. The better of two tries is recorded. The same procedure is followed for the left side. The score for lateral spinal fexion is calculated by averaging the best values for the left and the right side • intermalleolar distance - The patient is lying with the legs separated as far as possible with the knees straight and the toes pointing upwards. The distance between the medial malleoli is measured in cm. Alternatively, the intermalleolar distance is measured with the patient standing erect and the legs separated as far as possible. The better of two tries is recorded. BASMI 3-point scale 0 Mild* 1 Moderate 2 Severe Lateral lumber fexion >10 cm 5–10 cm <5 cm Tragus to wall distance 15 cm 15–30 cm >30 cm Lumbar fexion (modifed Schober) >4 cm 2–4 cm <2 cm Maximal intermalleolar distance >100 cm 70–100 cm <70 cm Cervical rotation >70∞ 20–70∞ <20∞ Score=sum of points for all fve measurements * normal values ref: Jenkinson TR, Mallorie PA, Whitelock HC, Kennedy LG, et al. The Bath AS Metrology Index. J Rheumatol. 1994;21(9):1694–8. Additional ASAS recommended mobility measures • Occiput to wall distance - The patient is standing with the heels and back resting against the wall, with the hips and knees as straight as possible. The chin should be held at the usual carrying level. The patient is asked to put maximal effort to touch the head against the wall. The distance between occiput and wall is measured in cm to the nearest 0.1 cm. The OWD is measured twice, and the better of two tries is recorded. • Chest expansion - The patient is asked to rest his hands on or behind the head. The difference between maximal inspiration and expiration is measured at the fourth intercostal level anteriorly in cm to the nearest 0.1 cm. Chest expansion 2.5-5.5 cm is considered normal (normal values should be correlated to age and sex) and < 2.5 cm is considered abnormal. 23
Enthesitis assessment - Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) The Maastricht ankylosing spondylitis enthesitis score (MASES), developed in patients with AS, has been used in AS and AxSpA consistently, with good performance. • MASES is a validated score mainly used in research. • Thirteen sites are assessed: - Costochondral 1 right/left (a) - Costochondral 7 right/left (b) - Spina iliaca anterior superior right/left (c) - Crista iliaca right/left (d) - Spina iliaca posterior right/left (e) - Processus spinosus L5 (f) - Achilles tendon, insertion right/left (g) • All sites are scored as 0 or 1 • The MASES is the sum of all site scores (from 0 to 13) ref: Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 2003;62:127–32. Mease PJ. Arthritis Care Res 2011;63(S11):S64–S85 (a) (b) (c) (e) (f) (d) (g) 1st Costochondral joint (L,R) (a) 7th Costochondral joint (L,R) (b) Anterior superior iliac spine (L,R) ( c ) Inferior margin of tenth costal cartilage Anterior superior iliac spine Pubic symphysis Achilles tendon insertion (L,R) C7 spinous process (vertebra prominens) T3 spinous process Scapular spine T7 spinous process Inferior angle of scapula T12 spinous process L4 spinous process ilac cres Posterior superior ilac spine S2 spinous process Posterior superior iliac spine (L,R) Iliac crest (L,R) T3 T7 T10 T12 IC IC PSIS PSIS T3 T7 T12 L4 S2 Spinous process of L5 24
1. Putting on your socks or tights without help or aids (e.g.sock aid) easy impossible 012345678910 2. Bending forward from the waist to pick up a pen from the foor without an aid easy impossible 012345678910 3. Reaching up to a high shelf without help or aids (e.g. helping hand) easy impossible 012345678910 4. Getting up out of an armless dining room chair without using your hands or any other help easy impossible 012345678910 5. Getting up off the foor without help from lying on you back easy impossible 012345678910 6. Standing unsupported for 10 minutes without discomfort easy impossible 012345678910 7. Climbing 12-15 steps without using a handrail or walking aid, one foot on each step easy impossible 012345678910 8. Looking over your shoulder without turning your body easy impossible 012345678910 9. Doing physically demanding activities (e.g. physiotherapy exercises, gardening or sports) easy impossible 012345678910 10. Doing a full day's activities whether it be at home or at work easy impossible 012345678910 Assessment of Function BASFI BASFI is a patient-reported outcome that includes 10 questions; 8 of them refer to aspects of functional anatomy, and 2 pertain to the ability to cope with everyday life. All questions are completed on numerical rating scales or on a 10 cm visual analog scale (VAS) with “easy” and “impossible” as anchors. The total BASFI-score is the average of the 10 questions and ranges from 0 to 10. ref: Calin A, Garrett S, Whitelock H, Kennedy LG et al. J Rheumatol. 1994;21(12):2281–5. 25
a. ASAS 20 improvement criteria ASAS20 is defned as an improvement of at least 20% and an absolute improvement of at least 1 unit on a 0-10 scale in at least three of the following domains: - patient global (0-10) - patient pain (0-10) - function (assessed by BASFI) - infammation (mean of BASDAI questions 5 and 6) In the remaining domain, there should be no worsening of 20 % and a minimum of 1 unit, on a 0 to 10 scale. ref: Anderson JJ, Baron G, van der Heijde D, Felson DT, Dougados M. Arthritis Rheum. 2001;44:1876–86. b. ASAS 40 improvement criteria ASAS40 is defned as an improvement of at least 40% and an absolute improvement of at least 2 units on a 0-10 scale in at least three of the following domains: - patient global (0-10) - patient pain (0-10) - function (assessed by BASFI) - infammation (mean of BASDAI questions 5 and 6) In the remaining domain, there should be no worsening in the fourth domain. ref: Brandt J, Listing J, Sieper J, Rudwaleit M, et al. Ann Rheum Dis. 2004;63:1438–44. c. ASAS 5/6 improvement criteria The ASAS 5/6 improvement criteria = an improvement of at least 20% in at least fve of these six domains: - patient global (0-10) - patient pain (0-10) - function (assessed by BASFI) - infammation (mean of BASDAI questions 5 and 6) - CRP - spinal mobility (assessed by lateral spinal fexion) ref: Brandt J, Listing J, Sieper J, Rudwaleit M, et al. Ann Rheum Dis. 2004;63:1438–44. d. ASAS partial remission ASAS has defned a state of partial remission, which refects very low disease activity. In order to fulfll an ASAS partial remission state, a value of 2 (on a 0 to 10 scale) or less should be present in each of the following domains: patient global, pain, function (BASFI), and infammation (mean of BASDAI questions 5 and 6). ref: Brandt J, Listing J, Sieper J, Rudwaleit M, et al. Ann Rheum Dis. 2004;63:1438–44. e. BASDAI 50 response Response to a treatment is defned by improvement of at least 50 % in the BASDAI score or an absolute change of 2 units (on a 0 to 10 scale) after 3 months of treatment with TNF- inhibitors, together with an expert opinion compatible with improvement. ref: Braun J, Davis J, Dougados M, Sieper J, et al. Ann Rheum Dis. 2006;65(316–320). f. ASDAS improvement criteria ASAS has also defned ASDAS-based response criteria. According to the ASDAS improvement criteria, a change in the score of at least 1.1 units is equivalent to a “clinically important improvement,” and a change of at least 2.0 units is called a “major improvement” ref: Machado P, Landewé R, Lie E. et al. Ann Rheum Dis. 2011;70(1):47–53. g. ASDAS inactive disease ASAS has defned cutoffs for disease activity states, using the ASDAS score. A value below 1.3 is considered “inactive disease”. ref: Machado P, Landewé R, Lie E. et al. Ann Rheum Dis. 2011;70(1):47–53. • Clinically Important ASDAS ≥1.1 improvement The ASAS Response Criteria Response criteria are intended to measure a response to treatment. The ASAS-defned improvement criteria as well as BASDAI and ASDAS can be used for defning improvement or response in both clinical practice and in studies. • Major ASDAS ≥2.1 improvement 26
הינו כלי מרכזי SLEDAI 2K . מדד ה- BILAG ו- SLEDAI-2K קיימים מספר כלים מחקריים להערכת פעילות זאבת. שני הכלים המרכזיים הינם פריטים עם ניקוד משתנה בהתאם למערכת 24 במרפאה לקביעת רמת פעילות זאבת בשלושים יום האחרונים. המדד כולל הערכה של ). המדד נמצא גם בקשר לתמותה ולנזק EULAR המעורבת. זהו כלי יעיל המשמש לקבלת החלטות טיפוליות (בהתאם לקווים המנחים של המצטבר כתוצאה מזאבת. החסרונות העיקריים שלו: מדובר במדד דיכוטומי שאינו לוקח בחשבון את חומרת התסמינים, שיפור שלהם ואת סוג הטיפול התרופתי שניתן. המדד אינו כולל גם התייחסות למעורבות דרכי עיכול או אנמיה המוליטית. מופעים קליניים בחודש האחרון, בהשוואה לחודש שקדם לו. הציון 86 כולל את רמת פעילות זאבת בתשעה איברים ו- BILAG מדד ה- הסופי מתורגם לאותיות לפי רמת הטיפול הנדרשת. מדובר בכלי מחקרי בעיקרו ופחות נפוץ בשימוש שגרתי במרפאה, אם כי הוא מאפשר להעריך גם שיפור או החמרה של התסמינים. חסרונות המדד הינם המורכבות שלו והעובדה שכל התסמינים מקבלים משקל זהה בחישוב הסופי של המדד. SLEDAIDescriptor Defnition 2K score 8 Seizure Recent onset, exclude metabolic, infectious or drug causes. Altered ability to function in normal activity due to severe disturbance in the 8 Psychoosis perception of reality. Altered mental function with impaired orientation, memory or other 8 Organic brain syndrome intellectual funcion. 8 Visual disturbance Retinal changes. 8 Cranial nerve disorder New onset of sensory or motor neuropathy involving cranial nerves Severe, persistent headache which may be migrainous, but must be 8 Lupus headache nonresponsive to narcotic analgesia. 8 Cerabrovascular accident New onset of cerebrovascular accident(s). Exclude arteriosclerosis. Ulceration, gangrene, tender fnger nodules, periungual infarction, splinter 8 Vasculitis haemorrhages, or biopsy or angiogram proof of vasculitis. ≥2 joints with pain and signs of infammation (i.e. tenderness, swelling or 4 Arthritis effusion). Proximal muscle aching/weakness, associated with elevated creatine 4 Myositis phosphokinase/aldolase or electromyogram changes or biopsy showing myositis. 4 Urinary casts Heme granular or red blood cell casts. 4 Haematuria >5 red blood cells/high power feld. Exclude stone, infection or other cause. 4 Proteinuria >0.5 gram/24 hours. 4 Pyuria >5 white blood cells/high power feld. Exclude infection. 2 Rash Infammatory type rash. 2 Alopecia Abnormal,patchy or diffuse loss of hair. 2 Mucosal ulcers Oral or nasal ulceration. 2 Pleurisy Pleuritic chest pain with pleural rub or effusion, or pleural thickenning. Pericardial pain with at least 1 of the following: rub, effusion, or 2 Pericarditis electrocardiogram or echocardiogram confrmation. 2 Low complement Decrease in CH50, C3 or C4. 2 Increased DNA binding Increased DNA binding by Farr assay. 1 Fever >38°C. Exclude infectious cause. 9 1 Thrombocytopenia <100 000 platelets / x10 /L, exclude drug causes. 9 1 Leukopenia <3000 white blood cells / x10 /L, exclude drug causes. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002;29:288-91 Systemic Lupus Erythematosus Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) 27
Drugs used in the treatment of SLE Figure 1 Treatment of non-renal SLE-recommended drugs with respective grading of recommendation. aPL, aniphospholipid antibodies; AZA, azathioprine; BEL, belimumab; BILAG: British Isles Lupus Assessment Group disease activity index; CNIs, calcineurin inhibitors; CYC, cyclophosphamide; GC, glucocorticoids; HCQ, hydroxychloroquine; IM, intramuscular; MMF, mycophenolate mofetil; MTX, methotrexate; Pre, predinisone; PO, per os; RTX, rituximab, PLTs: Platelets; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosusAnnals of the Rheumatic Diseases 2019;78:736-745. Treatment of non-renal Systemic Lupus Erythematosus Adjunct: Sun protection Vaccinations Exercise No soking Body weight Blood pressure Lipids Glucose Antiplatelets anti-coagulants (in aPL-positive patient) Target Remission SLEDAI = 0 HCQ No GC or Low disease activity SLEDAI ≤ 4 HCQ Pre ≤ 7.5 mg/d Immunosuppressives (in stable doses and well-tolerated) Mild* HCQ GC PO/IM MTX /AZA BEL GC PO/IV st 1 line st 1 line st 1 line Refractory Refractory Refractory CYC RTX Moderate* Severe* CNI MMF Grade A Grade B Grade C Grade D 3 3- Mild: constitutional symptoms / mild arthritis / rash ≤9% BSA/PLTs 50-100 x 10 /mm . SLEDAI≤6: BILAG C or ≤1 BILAG B manifestation Moderate: RA-like arthritis / rash 9-18% BSA/cutaneous vasculitis ≤18% BSA; PLTs 20*50 *103/mm/serosities; SLEDAI 7-12; ≥2 BILAG B manifestations Severe: major organ threatening disease (nephritis, cerebritis, myelitis, pneumonitis, mesenteric vasculitis; thrombocytopenia with platelets <103* 20/mm; TTP-like disease or acute hemophagocytic syndrome; SLEDAI>12; ≥1 BILAG A manifestations 28
Clinical response criteria of lupus nephritis according to current guidelines Guideline Complete Response Criteria Partial Response Criteria No Response KDIGO Decline in UPCR to ≤0.5 g/g >50% decrease in UPCR; if there Failure to achieve a complete or (≤50mg/mmol); return of Scr to was nephrotic-range proteinuria, then partial remission previous baseline reduction to <3,000 mg/g [<300 mg/ mmol] also; stabilization (±25%), or improvement of Scr, but no to normal ACR UPCR <0.2 g/g; normal Scr, or 25% UPCR of 0.2-2 g/g; eGFR at baseline No change or worsening improvement in eGFR if abnormal at level or improves 25% if abnormal at proteinuria; decline in eGFR by LN fare; inactive urine sediment LN fare; inactive urine sediment ≥25%; active urine sediment EULAR/ERA- UPCR <0.5 g/g; (50 mg/mmol); ≥50% reduction in UPCR, to less than <50% reduction in proteinuria or EDTA GFR within 10% of previous normal nephrotic range; near-normal GFR persistent nephrotic proteinuria; (within 10% of prior baseline) by 12 abnormal GFR (>10% decrease mo of treatment from prior baseline) Dutch SLE Proteinuria <0.5 g/24 h; Scr within Reduction in proteinuria by >50% to Persistent proteinuria with <50% Working Group 25% of baseline before fare <3 g/24 h; Scr within 25% of prior reduction or persistently >3g/24h baseline by 6-12 mo of treatment after 6-12 mo; doubling of Scr within 3 mo of starting therapy Abbreviations: ACR, American College of Rheumatology; eGFR, estimated glomerular fltration rate; EULAR/ERA-EDTA, European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association; GFR, glomerular fltration rate; KDIGO, Kidney Disease: Improvin Global Outcomes; LN, lupus nephritis; Scr, serum creatinine; SLE, Systemic lupus erythematosus; UPCR, urinary protein-creatinine ratio. Parikh SV, Almaani S, Brodsky S et al. Update on Lupus Nephritis: Core Curriculum 2020. Am J Kidney Dis. 2020 Aug;76(2):26. Epub 2020 Mar 24. חודשים נמצא כמדד הפרוגנוסטי היחיד הטוב ביותר לניבוי הדרדרות כליתית או הגעה לאי ספיקת כליות סופנית 12 פרוטאינוריה בבחולות עם לופוס נפריטיס. The Safety of Estrogen in Lupus Erythematosus National Assessment (SLENA) trial defnitions of fare 'mild/moderate fare' 'Severe fare' • a change in SLEDAI ≥3 points, or • change in SLEDAI >12, or • new/worse skin, stomatitis, serositis, arthritis, fever, or • new/worse CNS-SLE, vasculitis, nephritis, myositis, Plt < 60,000 hemolytic ane- • increased prednisone <0.5mg/kg/d, or mia with Hb <7 mg/dl, requiring doubling or >0.5 mg/kg/d prednisone, or • added NSAID/Plaquenil, or • hospitalization for SLE, or • ≥1.0 increase in a physician's global assessment (0-3 scale) • prednisone > 0.5 mg/kg/d, or • new immunosuppressive, or • increase in physician's global assessment to > 2.5 Petri M, Buyon J, Kim M. Classifcation and defnition of major fares in SLE clinical trials. Lupus. 1999;8(8):685-691. מדד פרקטי להערכה של התלקחות זאבת, בנוסף להערכה של רמת פעילותה. , בנוסף למספר פרמטרים פשוטים הנלקחים במרפאה כגון שינוי קליני, שינוי תרופתי והערכת הרופא המטפל SLEDAI המדד מורכב מ- .)0-3 (בסקאלה של Scoring of the British Isles Lupus Assessment Group (BILAG) E M Hay, P A Bacon, C Gordon et al. The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 1993 Jul;86(7):447-58. Letter Defnition Categorization A Severe disease requiring increases in prednisone to >20 mg/day and/or the addition of immunosuppressive agents B LESS ACTIVE disease requiring low-dose prednisone and/or symptomatic treatment with NSAIDs and/or antimalarials C Mild disease requiring symptomatic therapy such as simple analgesics or stable disease on current therapy D Previous organ system involvement without current disease activity E No previous or current disease involvment in that organ system 29
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