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that time. Serum samples were collected   Table 1. Baseline characteristics of patients from both groups
          from the patients just before the first
          apheresis procedure and one week after                                        LCAP group  Control group
          the last one. These samples were stored   Characteristics                      (n = 20)    (n = 31)
          at -80°C until the cytokine analysis was   Demographics
          performed.                            Sex (% female)                           87.50%      87.10%
                                                Age, years                             46.00 ± 16.06  49.00 ± 12.84
          Intervention                        RA activity
             LCAP was performed using a direct   Mean disease duration, months            22.16       24.95
          hemoperfusion column, a Cellsorba     Tender joint count (range, 0–28)        14.31 ± 9.4  10.45 ± 7.91
          column (CS-180S; Asahi Kasei Medical,   Swollen joint count (range, 0–28)     8.68 ± 7.71  9.54 ± 6.14
          Tokyo, Japan), to remove circulating   Patient assessment of pain, VAS (range, 0–10)  5.18 ± 1.51  5.90 ± 1.01
          leukocytes from the patients’ blood. The   Patient assessment of global severity, VAS (range, 0–10)  5.37 ± 1.66  6.20 ± 0.94
          column is packed with fine-diameter   Physician assessment of global severity, VAS (range, 0–10)  5.28 ± 1.50  5.67 ± 0.90
          polyethylene terephthalate fibers that are   ESR,mm/h                        38.75 ± 27.55  46.35 ± 30.99
          commonly used for adsorbing white     CRP,mg/dL                               4.46 ± 3.91  3.01 ± 2.34
          blood cells to prevent febrile,       DAS28                                   5.81 ± 1.29  5.80 ± 1.36
          nonhemolytic transfusion reaction     HAQ-DI                                  6.93 ± 6.89  5.58 ± 3.87
          during blood transfusion. 3,19
             Briefly, when whole blood is passed   Note: values are the mean ± SD.
          through  the  fiber  layer  in  the  cylinder,
          leukocytes—including  monocytes,   Abbreviations: LCAP, leukocytapheresis; RA, rheumatoid arthritis;
          neutrophils, and lymphocytes—are   HAQ-DI, Health Assessment Questionnaire Disability Index; VAS, visual analog
          trapped and filtered by the fiber layer. In   scale; CRP, C-reactive protein; ESR erythrocyte sedimentation rate.
          each apheresis procedure in the current
          study, 3000 mL of whole blood were filtered and returned to   The DAS has been developed as a quantitative index to
          each patient. The column was mounted on the machine for   be able to measure, study and manage disease activity in RA
          extracorporeal circulation  (PlasautoiQ21,  Asahi Kasei   in daily clinical practice, clinical trials, and long term
          Medical) and was perfused with blood at a flow rate of    observational studies. The most widely used method for RA
          50 mL/min for 60 minutes with the aid of a peristaltic pump.   activity evaluation is the DAS and its simplified version –
          Sodium heparin was infused into the outlet line initially at a   DAS28. DAS score was developed in Nijmegen, the
          rate of 30 mg/h and then at 10 mg/h as a local anticoagulant.   Netherlands. The development began in 1983 for the purpose
          The apheresis procedure was performed every 5 days for a   of assessment of RA activity for a clinical study and was
          total of 5 treatments.                             continued for several years thereafter. DAS/DAS28 is a
                                                             continuous measure of RA disease activity that combines
          Outcome Measures                                   information  from  Swollen-joint  count,  Tender-joint  count,
             American College of Rheumatology (ACR) recommend   acute phase response including ESR, CRP, and patient
          the Clinical Disease Activity Index, Disease Activity Score   self-report  of general  health  which  call  The VAS  assesses
          (DAS) with 28-joint counts (erythrocyte sedimentation rate   patients’ pain. Cut points were developed to classify patients
          or C-reactive protein), Patient Activity Scale (PAS), PAS-II,   in remission, as well as low, moderate, and severe disease
          Routine Assessment of Patient Index Data with 3 measures,   activity in the 1990s.
          and Simplified Disease Activity Index because they are   DAS28 score is currently used in clinical practice more
          accurate reflections of disease activity; 20,21  are sensitive to   commonly than the DAS score because it requires assessment
          change; discriminate well between low, moderate, and high   of fewer joints (only 28 joints are assessed for the DAS28
          disease activity states; have remission criteria; and are feasible   score). Twenty-eight tender and swollen joint scores include
          to perform in clinical settings.                   the same joints: shoulders, elbows, wrists, metacarpophalangeal
             Most clinical studies on  RA have included  clinical   joints, proximal interphalangeal joints and the knees.
          outcomes, such as the ACR definition of improvement, the   More recently, an alternative formulation of the DAS28
          DAS, and disease-specific quality of life (QoL), such as health   based on CRP has been proposed and developed.
          assessment questionnaire disability index (HAQ-DI).   In clinical trials the DAS28 can be used to assess whether
             In rheumatoid arthritis, disease activity cannot be   an individual patient has a significant improvement of the
          measured using a single variable. Current EULAR diagnostic   disease activity, compared to baseline. For this aim, the
          criteria for RA include disease activity parameters, such as   EULAR response criteria can be used. The DAS28 can be
          erythrocyte sedimentation rate (ESR) and C-reactive protein   calculated with the CRP instead of the ESR. The C-reactive
          (CRP), which are used to calculate disease activity scores,   protein (CRP) may be used as an alternative to ESR in the
          including DAS and DAS28.                           calculation of the DAS or the DAS28. The DAS28 can be


           38   ALTERNATIVE THERAPIES, JUL/AUG 2020 VOL. 26 NO. 4    Huang—Leukocytapheresis Therapy for Rheumatoid Arthritis
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