Vol 48, No 4 (2010)
Articles
14-26 957
Abstract
Objective: To evaluate the impact of rituximab (RTM) therapy on the clinical, morphological, and immunological parameters of lupus
nephritis (LN) activity.
Subjects and methods. The study included 19 patients with types III and IV LN (WHO classification) with its 6-133-month history. Their
mean age was 28,6 years (18-63 years). RTM was given in a dose of 500 mg weekly for 4 weeks or 1000 mg twice at an interval of 2
weeks. Fourteen patients received a complete course of RTM therapy. Five cases could not complete the course due to poor tolerability or
death. Renal rebiopsy was performed in 8 patients 6-12 months after therapy initiation.
Results. Thirteen patients achieved partial remission in different follow-up periods. Complete remission was noted in 7 patients a year after a
course of RTM therapy. There were no exacerbations of LN in remission patients. Just a month after therapy was marked by a decline in the
systemic lupus erythematosus disease activity index (SLEDAI 2K) from 20.4+7.3 to 14.3+6.5 (p<0.05). A significant anti-dsDNA antibody
titer decrease and C3 and C4 normalization were detectable at 3-6-12 months. Overall, RTM therapy proved to be effective in 13 (68%) of
the 19 patients. Morphological re-examination of renal biopsy specimens revealed that all cases had a considerable average reduction in morphological
activity index from 8 (6-9) to 3 (1-4) (p=0.027). Transformation of LN to its better type was found in 5 cases. RTM therapy
turned out to be ineffective in 6 patients with evident renal failure. There were no serious adverse reactions and complications after RTM use.
Conclusion. RPM therapy results in a reduction in the clinical, laboratory, and morphological activity of LN in most cases provided that
renal nitrogen-excretory function is preserved at therapy start.
nephritis (LN) activity.
Subjects and methods. The study included 19 patients with types III and IV LN (WHO classification) with its 6-133-month history. Their
mean age was 28,6 years (18-63 years). RTM was given in a dose of 500 mg weekly for 4 weeks or 1000 mg twice at an interval of 2
weeks. Fourteen patients received a complete course of RTM therapy. Five cases could not complete the course due to poor tolerability or
death. Renal rebiopsy was performed in 8 patients 6-12 months after therapy initiation.
Results. Thirteen patients achieved partial remission in different follow-up periods. Complete remission was noted in 7 patients a year after a
course of RTM therapy. There were no exacerbations of LN in remission patients. Just a month after therapy was marked by a decline in the
systemic lupus erythematosus disease activity index (SLEDAI 2K) from 20.4+7.3 to 14.3+6.5 (p<0.05). A significant anti-dsDNA antibody
titer decrease and C3 and C4 normalization were detectable at 3-6-12 months. Overall, RTM therapy proved to be effective in 13 (68%) of
the 19 patients. Morphological re-examination of renal biopsy specimens revealed that all cases had a considerable average reduction in morphological
activity index from 8 (6-9) to 3 (1-4) (p=0.027). Transformation of LN to its better type was found in 5 cases. RTM therapy
turned out to be ineffective in 6 patients with evident renal failure. There were no serious adverse reactions and complications after RTM use.
Conclusion. RPM therapy results in a reduction in the clinical, laboratory, and morphological activity of LN in most cases provided that
renal nitrogen-excretory function is preserved at therapy start.
26-31 1352
Abstract
Objective: To study the time course of changes in the indices of the blood lipid spectrum in patients with rheumatoid arthritis (RA) treated
with rituximab during a 24-week follow-up.
Subjects and methods. The study enrolled 39 patients (36 females and 3 males) with a valid diagnosis of RA; their mean age was 50 years;
disease duration 93.5 months; duration activity scale (DAS) 6.1 scores. A previous ineffective treatment with methotrexate was found in 6
patients; that with two basic anti-inflammatory drugs or more in 30, and previous TNF- inhibitor therapy failed in 14 of the 39 patients.
The blood lipid spectrum and intima-media thickness (IMT) were determined before and 24 weeks after the first injection of rituximab.
The drug was intravenously administered dropwise in a dose of 1000 mg twice at a 14-week interval. Therapeutic efficiency was estimated
according to the RA activity index - DAS28. All the patients showed a satisfactory/good response to rituximab therapy.
Results. There was a double reduction in the frequency of hypoalfalipoproteinemia and in the increased atherogenicity index (AI). Elevated
cholesterol (CH), triglycerides (TG), and low-density lipoprotein (LDL CH) levels were found in equal frequencies before and 24 week
after rituximab administration. There was a 5% rise in CH concentrations, a considerable (22%) increase in high-density lipoprotein CH,
and an 18.6% decrease in AI (p<0.05 in all cases). The levels of LDL CH and TG tended to increase; however, they failed to achieve statistical
significance. The change in the spectrum of lipids and blood lipoproteins was associated with the pronounced decline in disease
activity (decreases in C-reactive protein concentrations, erythrocyte sedimentation rate, IgM rheumatoid factor, and DAS28 index) and
better patient functional status (Health Assessment Questionnaire (HAQ) index) (p<0.05). There was a significant reduction in the maximum
carotid IMT in patients with RA: it was 1.09 (0.94-1.2) and 0.95 (0.8-1.3) mm before and 24 weeks after rituximab administration,
respectively (p=0.001).
with rituximab during a 24-week follow-up.
Subjects and methods. The study enrolled 39 patients (36 females and 3 males) with a valid diagnosis of RA; their mean age was 50 years;
disease duration 93.5 months; duration activity scale (DAS) 6.1 scores. A previous ineffective treatment with methotrexate was found in 6
patients; that with two basic anti-inflammatory drugs or more in 30, and previous TNF- inhibitor therapy failed in 14 of the 39 patients.
The blood lipid spectrum and intima-media thickness (IMT) were determined before and 24 weeks after the first injection of rituximab.
The drug was intravenously administered dropwise in a dose of 1000 mg twice at a 14-week interval. Therapeutic efficiency was estimated
according to the RA activity index - DAS28. All the patients showed a satisfactory/good response to rituximab therapy.
Results. There was a double reduction in the frequency of hypoalfalipoproteinemia and in the increased atherogenicity index (AI). Elevated
cholesterol (CH), triglycerides (TG), and low-density lipoprotein (LDL CH) levels were found in equal frequencies before and 24 week
after rituximab administration. There was a 5% rise in CH concentrations, a considerable (22%) increase in high-density lipoprotein CH,
and an 18.6% decrease in AI (p<0.05 in all cases). The levels of LDL CH and TG tended to increase; however, they failed to achieve statistical
significance. The change in the spectrum of lipids and blood lipoproteins was associated with the pronounced decline in disease
activity (decreases in C-reactive protein concentrations, erythrocyte sedimentation rate, IgM rheumatoid factor, and DAS28 index) and
better patient functional status (Health Assessment Questionnaire (HAQ) index) (p<0.05). There was a significant reduction in the maximum
carotid IMT in patients with RA: it was 1.09 (0.94-1.2) and 0.95 (0.8-1.3) mm before and 24 weeks after rituximab administration,
respectively (p=0.001).
31-40 945
Abstract
Objective: To evaluate the functional status of patients with rheumatoid arthritis (RA) receiving two courses of rituximab (RTМ) therapy
and its efficiency from the Russian registrys data.
Subjects and methods. The analysis covered 269 patients receiving 1 or 2 courses of RT therapy, their clinical follow-up schedules and
quality of life (QL) questionnaires were filled in before drug administration and at 8, 16, and 24 weeks of a follow-up: 220 and 49 patients
received 1 and 2 courses of RT therapy, respectively. The DAS28 index was used to evaluate disease activity; the patients functional status
was assessed according to the Health Assessment Questionnaire (HAQ).
Results. The patients' mean age was 46.5311.79 years; the disease duration was 9.806.87 years; disease activity scale (DAS28) scores
were 6.501.06; the majority of patients had significant functional disorders estimated at 1.90 [1.37-2.38] scores according to the HAQ;
78% patients had extra-articular manifestations; rheumatoid factor was detected in 82.9%; the patients received more than 2 basic antiinflammatory
drugs on average; 33.5% took TNF-р inhibitors.
After the first course of therapy at 24 weeks of the follow-up, there was a gradual decline in DAS28 from 6.491.05 to 4.091.32 scores (p
< 0.000001, ANOVA). A significant reduction in serum C-reactive protein was achieved during the first course of therapy just at 2 weeks of
the follow-up. A decrease in DAS28 to і1.2 was seen in 79.9 of the patients after the first course at 24 weeks of the follow-up and in 85.7%
after the second course. 13% of patients achieved drug-induced remission (DAS28 <2.6) at 24 weeks of the follow-up after the first course
of RT therapy; the proportion of remission patients increased up to 14.3% after the second course.
Median HAQ index decreased by 0.52, 0.77, and 0.78 scores at 8, 16, and 24 weeks of follow-up, respectively; 15% of the patients had
population-based functional status values at 24 follow-up weeks.
Logistic regression analysis indicated that the previous use of TNF- inhibitors was a predictor of the response to RT therapy during the
first course; odds ratio (OR) = 2.27 [1.07-4.80].
Conclusion. RTМ therapy substantially improved functional capacities in patients with RA. Previous therapy with TNF- inhibitors had no
negative impact on the results of treatment.
and its efficiency from the Russian registrys data.
Subjects and methods. The analysis covered 269 patients receiving 1 or 2 courses of RT therapy, their clinical follow-up schedules and
quality of life (QL) questionnaires were filled in before drug administration and at 8, 16, and 24 weeks of a follow-up: 220 and 49 patients
received 1 and 2 courses of RT therapy, respectively. The DAS28 index was used to evaluate disease activity; the patients functional status
was assessed according to the Health Assessment Questionnaire (HAQ).
Results. The patients' mean age was 46.5311.79 years; the disease duration was 9.806.87 years; disease activity scale (DAS28) scores
were 6.501.06; the majority of patients had significant functional disorders estimated at 1.90 [1.37-2.38] scores according to the HAQ;
78% patients had extra-articular manifestations; rheumatoid factor was detected in 82.9%; the patients received more than 2 basic antiinflammatory
drugs on average; 33.5% took TNF-р inhibitors.
After the first course of therapy at 24 weeks of the follow-up, there was a gradual decline in DAS28 from 6.491.05 to 4.091.32 scores (p
< 0.000001, ANOVA). A significant reduction in serum C-reactive protein was achieved during the first course of therapy just at 2 weeks of
the follow-up. A decrease in DAS28 to і1.2 was seen in 79.9 of the patients after the first course at 24 weeks of the follow-up and in 85.7%
after the second course. 13% of patients achieved drug-induced remission (DAS28 <2.6) at 24 weeks of the follow-up after the first course
of RT therapy; the proportion of remission patients increased up to 14.3% after the second course.
Median HAQ index decreased by 0.52, 0.77, and 0.78 scores at 8, 16, and 24 weeks of follow-up, respectively; 15% of the patients had
population-based functional status values at 24 follow-up weeks.
Logistic regression analysis indicated that the previous use of TNF- inhibitors was a predictor of the response to RT therapy during the
first course; odds ratio (OR) = 2.27 [1.07-4.80].
Conclusion. RTМ therapy substantially improved functional capacities in patients with RA. Previous therapy with TNF- inhibitors had no
negative impact on the results of treatment.
40-48 959
Abstract
Genetic engineering biologicals (GEBs) show promises in treating rheumatoid arthritis (RA), their efficacy and tolerability have been studied
and indications and contraindications defined. However, the extensive application of GEBs is limited due to their high cost. In Russia,
GEB therapy is paid by the government. To plan and optimize expenditures, it is necessary to have standardized indications and to know
the number of patients who need biological therapy.
Objective: To define a need for GEBs (tumor necrosis factor- (TNF-) inhibitors) in patients with RA in real clinical practice in Russia.
Subjects and methods. The study comprised 2 stages. At Stage 1, the expert method was used to develop a standardized scale to define indications
for GEB therapy in patients with RA (StansRA). Disease activity (DAS 28) and duration, progression rate, and tolerability of earlier
used basic anti-inflammatory drugs, including methotrexate (MT) in a dose of ≥15 mg/week were considered. Each index was estimated as
scores. According to the total scores (min 0, max 0), the patients were divided into 4 groups: 1) GEBs are absolutely indicated (≥7 scores);
2) more likely indicated (5-6 scores); 3) more unlikely indicated (3-4 scores); 4) absolutely contraindicated (<3 scores). At Stage 2, a
total of 1810 patients with RA (mean age 54.111.4 years; male/female ratio 1:5.2) who met the 1987 ACR criteria were simultaneously
examined in the clinics of 23 Russias regions. The mean disease duration was 8.8 years (min 3 months; max 30 years); DAS 28 5.51.4.
There were predominant patients with moderate (DAS 28 3.2-5.1) and high (DAS 28 >5.1) RA activity (27 and 65%, respectively). 69%
took MT (mean dose 12.52.5 mg).
Results. 4.4% of the 1810 patients had contraindications for GEB therapy. According to the StansRA, GEB therapy is absolutely contraindicated
in 6% of cases and 52.7% had indications for GEB use (absolutely and more likely indicated in 9.5 and 43%, respectively). Of
them, only 7 (0.5%) patients collected the maximum (9) scores; 33 (2.2%) patients had 8 scores; 101 (6.8%) had 7 scores.
Conclusion. The StansRA developed and tested at the population level aids in reducing subjectivism to use these medicines and in optimizing
financial expenses on the treatment of patients with RA in real clinical practice in Russia.
and indications and contraindications defined. However, the extensive application of GEBs is limited due to their high cost. In Russia,
GEB therapy is paid by the government. To plan and optimize expenditures, it is necessary to have standardized indications and to know
the number of patients who need biological therapy.
Objective: To define a need for GEBs (tumor necrosis factor- (TNF-) inhibitors) in patients with RA in real clinical practice in Russia.
Subjects and methods. The study comprised 2 stages. At Stage 1, the expert method was used to develop a standardized scale to define indications
for GEB therapy in patients with RA (StansRA). Disease activity (DAS 28) and duration, progression rate, and tolerability of earlier
used basic anti-inflammatory drugs, including methotrexate (MT) in a dose of ≥15 mg/week were considered. Each index was estimated as
scores. According to the total scores (min 0, max 0), the patients were divided into 4 groups: 1) GEBs are absolutely indicated (≥7 scores);
2) more likely indicated (5-6 scores); 3) more unlikely indicated (3-4 scores); 4) absolutely contraindicated (<3 scores). At Stage 2, a
total of 1810 patients with RA (mean age 54.111.4 years; male/female ratio 1:5.2) who met the 1987 ACR criteria were simultaneously
examined in the clinics of 23 Russias regions. The mean disease duration was 8.8 years (min 3 months; max 30 years); DAS 28 5.51.4.
There were predominant patients with moderate (DAS 28 3.2-5.1) and high (DAS 28 >5.1) RA activity (27 and 65%, respectively). 69%
took MT (mean dose 12.52.5 mg).
Results. 4.4% of the 1810 patients had contraindications for GEB therapy. According to the StansRA, GEB therapy is absolutely contraindicated
in 6% of cases and 52.7% had indications for GEB use (absolutely and more likely indicated in 9.5 and 43%, respectively). Of
them, only 7 (0.5%) patients collected the maximum (9) scores; 33 (2.2%) patients had 8 scores; 101 (6.8%) had 7 scores.
Conclusion. The StansRA developed and tested at the population level aids in reducing subjectivism to use these medicines and in optimizing
financial expenses on the treatment of patients with RA in real clinical practice in Russia.
48-53 927
Abstract
Objective: To define the specific features of bone metabolism and to estimate bone mineral density (BMD) in patients with early rheumatoid
arthritis (ERA).
Subjects and methods. Fifty-three patients (9 males and 44 females) with ERA were examined. Markers of bone metabolism markers were
assessed, by measuring the serum levels of osteocalcin and C-terminal telopeptides (bCrosslaps) by electrochemoluminescence immunoassay
and those of type II interleukin (IL) 1 receptor (IL1RII) and IL-6 by enzyme-linked immunosorbent assay. Bone mineral density
(BMD) was studied by distal forearm densitometry (dual-energy X-ray absorptiometry) on a DexaScan DX-10 apparatus. BMD was estimated
in postmenopausal women by the T-test and in men and premenopausal women by the Z-test, as well as by the absolute value of
BMD (g/cm2).
Results. In patients with ERA, the level of bCrosslaps was 0.50.3 ng/ml (p<0.05) and that of osteocalcin was 209.9 ng/ml (p>0.05),
which is accordingly higher and lower than the reference values. There were no changes in these parameters in relation to serogroup and Xray
disease stage. With higher ERA activity, there was a tendency for bCrosslaps to increase and osteocalcin to remain unchanged. There
was a tendency towards decreased IL1 RII and increased proinflammatory IL-6 levels. Correlation analysis revealed a correlation between
the value of BMD and the content of bCrosslaps and osteocalcin in patients with ERA and between the levels of IL-6 and bCrosslaps.
Regression analysis showed a significant impact of the parameters of the course of the disease and immunological parameters on BMD
changes and bone metabolism markers. Age and body mass index also affected the parameters of BMD in patients with ERA.
arthritis (ERA).
Subjects and methods. Fifty-three patients (9 males and 44 females) with ERA were examined. Markers of bone metabolism markers were
assessed, by measuring the serum levels of osteocalcin and C-terminal telopeptides (bCrosslaps) by electrochemoluminescence immunoassay
and those of type II interleukin (IL) 1 receptor (IL1RII) and IL-6 by enzyme-linked immunosorbent assay. Bone mineral density
(BMD) was studied by distal forearm densitometry (dual-energy X-ray absorptiometry) on a DexaScan DX-10 apparatus. BMD was estimated
in postmenopausal women by the T-test and in men and premenopausal women by the Z-test, as well as by the absolute value of
BMD (g/cm2).
Results. In patients with ERA, the level of bCrosslaps was 0.50.3 ng/ml (p<0.05) and that of osteocalcin was 209.9 ng/ml (p>0.05),
which is accordingly higher and lower than the reference values. There were no changes in these parameters in relation to serogroup and Xray
disease stage. With higher ERA activity, there was a tendency for bCrosslaps to increase and osteocalcin to remain unchanged. There
was a tendency towards decreased IL1 RII and increased proinflammatory IL-6 levels. Correlation analysis revealed a correlation between
the value of BMD and the content of bCrosslaps and osteocalcin in patients with ERA and between the levels of IL-6 and bCrosslaps.
Regression analysis showed a significant impact of the parameters of the course of the disease and immunological parameters on BMD
changes and bone metabolism markers. Age and body mass index also affected the parameters of BMD in patients with ERA.
54-59 726
83-86 1159
Abstract
The paper describes a case of Gorham-Stout syndrome, a rare condition, which is accompanied by massive osteolysis of different portions
of bone tissue. It reviews the data available in the literature on this problem. Idiopathic osteolysis concurrent with chylothorax has a poor
prognosis. The syndrome can be treated only with calcitonins or bisphosphonates.
of bone tissue. It reviews the data available in the literature on this problem. Idiopathic osteolysis concurrent with chylothorax has a poor
prognosis. The syndrome can be treated only with calcitonins or bisphosphonates.
ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)
ISSN 1995-4492 (Online)