Objective To evaluate the efficacy and toxicity of methotrexate (MTX) in the treatment of ankylosing spondylitis (AS). Methods Randomized controlled trials (RCTs) were identified from CENTRAL (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to November 2005); EMBASE (1980 to November 2005); CINAHL (1982 to November 2005). The quality of included trials was evaluated. Data were extracted by two reviewers independently using a specially designed extraction form. The Cochrane Collaboration’s RevMan 4.2 software was used for data analysis. Results Three trials involving 116 patients were included. One 12-month trial compared naproxen plus MTX with naproxen alone. Two 24-week trials compared different doses of MTX with placebo. No statistically significant differences were found for the primary outcome measures of physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs and patient and physician global assessment. The response rate in one trial showed statistically significant benefits of 36% in the MTX group compared with the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was a composite index including assessment of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. However, no single outcome showed a statistically significant difference between the MTX and placebo groups when endpoint results were compared. Therefore, this benefit of MTX was questionable. No serious side effects were reported in these studies. Conclusions There is no enough evidence to show any benefit of MTX in the treatment of AS. High quality randomized controlled trials of longer duration and with larger sample size are needed to clarify the effect of MTX on AS.
ObjectiveTo evaluate the effectivity and safety of posterior osteotomy for thoracolumbar stress fracture in ankylosing spondylitis (AS) through the gap of a pathological fracture.MethodsBetween April 2012 and August 2015, 8 patients with AS combined with thoracolumbar stress fracture were treated with posterior osteotomy through the gap of a pathological fracture to correct the kyphosis. There were 7 males and 1 female, with an average age of 51 years (range, 37-74 years). The history of AS was 1-40 years (mean, 21.7 years) and disease duration of stress fracture was 2-60 months (mean, 18.5 months). The segmental lesions included T8, 9 in 1 case, T10, 11 in 2 cases, T11 in 2 cases, T12, L1 in 1 case, L1, 2 in 1 case, and L2, 3 in 1 case. The nerve function before operation according to Frankel grading was grade D in 3 cases and grade E in 5 cases. The pre- and post-operative X-ray films, CT three-dimensional reconstruction, and MRI were collected to measure the global kyphosis (GK), local kyphosis (LK), angle of the fusion levels (AFL), pelvic incidence (PI), pelvic tilt (PT), and sagittal vertical axis (SVA). Visual analogue scale (VAS) score was used to assess the back pain intensity.ResultsThe operation time was 210-320 minutes (mean, 267 minutes), and the intraoperative blood loss was 400-2 000 mL (mean, 963 mL). Cerebrospinal fluid leakage was found in 3 patients, and the wound healed by removal of drainage tube and suturing drainage outlet after 5-7 days of operation. The wounds of the rest patients healed by first intention. Lower extremity numbness occurred in 1 case and recovered after 1 month of postoperative administration of oral mecobalamin. All the patients were followed up 20-43 months (mean, 28.4 months). No internal fixator loosening, fracture, and other complications occurred. All the fractures healed with the healing time of 3-12 months (mean, 6.8 months). At 3 months after operation, 3 cases with spinal cord injury of preoperative Frankel grade D recovered to grade E. The GK, LK, AFL, PI, PT, SVA, and VAS scores at 1 week after operation and at last follow-up were significantly improved when compared with preoperative ones (P<0.05). Except for VAS score at last follow-up was significantly improved when compared with that at 1 week after operation (P<0.05), there was no significant difference in the other indexes between at 1 week after operation and at last follow-up (P>0.05).ConclusionPosterior osteotomy through the gap of a pathological fracture is a safe and effective surgical procedure for kyphosis correction and relief of back pain in AS patients combined with thoracolumbar stress fracture. Successful bony fusion and good clinical outcomes can also be achieved by this surgical procedure.
Objective To investigate the effect of the morphological changes in the proximal femur on the prothesis selection in the total hip arthroplasty in the patients with ankylosing spondylitis. Methods The experimental group was composed of 13 patients (16 hips) with ankylosing spondylitis, which was treated with the total hip arthroplasty, and the control group was composed of 16 patients（19 hips）with non-ankylosing spondylitis，which was also treated with the total hip arthroplasty. In the two groups, the measurements of Singh index，canal flare index，morphological index of the cortex and cortical index were performed in the two groups. Results The results of the statistical analysis on Singh index，canal flare index, morphological index of the cortex and cortical index in the experimental group were 3.81±0.54, 2.63±0.41, 2.02±0.38 and 1.69±0.69, respectively, but 4.63±0.62, 3.03±0.27, 2.76±0.28 and 2.12±0.24, respectively in the control group. Therewas a significant difference in Singh index, canal flare index, and morphological index of the cortex between the two groups (Plt;0.05)，while there was no statistical difference in cortical index between the two groups (P＞0.05). The patientswith ankylosing spondylitis had more serious osteoporosis in their proximal femur. Conclusion Cemented femoral prosthesis should be used in the total hip replacement in patients with ankylosing spondylitis, and the revision total hip arthroplasty should be performed on patients with more serious osteoporosis.
Objective To explore the safety and effectiveness of one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation in the treatment of ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. Methods A clinical data of 20 patients with ankylosing spondylitis kyphosis combined with acute thoracolumbar spine fracture, who were treated with one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation between April 2016 and January 2022, was retrospectively analyzed. Among them, 16 cases were male and 4 cases were female; their ages ranged from 32 to 68 years, with an average of 45.9 years. The causes of injury included 10 cases of sprain, 8 cases of fall, and 2 cases of falling from height. The time from injury to operation ranged from 1 to 12 days, with an average of 7.1 days. The injured segment was T11 in 2 cases, T12 in 2 cases, L1 in 6 cases, and L2 in 10 cases. X-ray film and CT showed that the patients had characteristic imaging manifestations of ankylosing spondylitis, and the fracture lines were involved in the anterior, middle, and posterior columns and accompanied by different degrees of kyphosis and vertebral compression; and MRI showed that 12 patients had different degrees of nerve injuries. The operation time, intraoperative bleeding, intra- and post-operative complications were recorded. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were used to evaluate the low back pain and quality of life, and the American spinal cord injury association (ASIA) classification was used to evaluate the neurological function. X-ray films were taken, and local Cobb angle (LCA) and sagittal vertical axis (SVA) were measured to evaluate the correction of the kyphosis. Results All operations were successfully completed and the operation time ranged from 127 to 254 minutes (mean, 176.3 minutes). The amount of intraoperative bleeding ranged from 400 to 950 mL (mean, 722.5 mL). One case of dural sac tear occurred during operation, and no cerebrospinal fluid leakage occurred after repair, and the rest of the patients did not suffer from neurological and vascular injuries, cerebrospinal fluid leakage, and other related complications during operation. All incisions healed by first intention without infection or fat liquefaction. All patients were followed up 8-16 months (mean, 12.5 months). The VAS score, ODI, LCA, and SVA at 3 days after operation and last follow-up significantly improved when compared with those before operation (P<0.05), and the difference between 3 days after operation and last follow-up was not significant (P>0.05). The ASIA grading of neurological function at last follow-up also significantly improved when compared with that before operation (P<0.05), including 17 cases of grade E and 3 cases of grade D. At last follow-up, all bone grafts achieved bone fusion, and no complications such as loosening, breaking of internal fixation, and pseudoarthrosis occurred. Conclusion One-stage posterior eggshell osteotomy and long-segment pedicle screw fixation is an effective surgical procedure for ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. It can significantly relieve patients’ clinical symptoms and to some extent, alleviate the local kyphotic deformity.
Objective To assess the midterm follow-up outcomes of total hip arthroplasty (THA) for the treatment of patients with juvenile-onset ankylosing spondylitis (JAS). Methods The clinical data of 81 patients (127 hips) with JAS (age≤16 years, JAS group) and 267 patients (391 hips) with adult onset ankylosing spondylitis (AAS) (age>16 years, AAS group) between January 2004 and March 2018 were retrospectively analysed. The baseline demographics, clinical, radiographic, and laboratory parameters were collected. Before operation and at last follow-up, the overall disease activity [Bath ankylosing spondylitis disease activity index (BASDAI)] and function status [Bath ankylosing spondylitis functional index (BASFI)], hip subjective score [Harris hip score (HHS)] and objective score [12-item short form health survey (SF-12), including physical component score (PCS) and mental component score (MCS)], and patient satisfaction for THA were reviewed. The major orthopedic complications, including periprosthetic infection, dislocation, periprosthetic fractures, and poor incision healing, were also recorded during the follow-up period. Results The comparison of preoperative baseline parameters showed that the body mass, body mass index, age of onset, age of surgery, disease duration, and the proportion of combined smoking history in the JAS group were significantly lower than those in the AAS group (P<0.05), the proportion of bilateral surgeries, proportion of uveitis, proportion of combined family history, C-reactive protein, albumin, and preoperative BASFI were significantly higher than those in the AAS group (P<0.05). Both groups were followed up. The follow-up time in the JAS group was 29-199 months, with an average of 113 months; in the AAS group was 35-199 months, with an average of 98 months. Incisions in both groups healed by first intention. During the follow-up period, there were 1 case of periprosthetic fracture, 1 case of dislocation, and 1 case of ceramic fragmentation in the JAS group, 1 case of periprosthetic infection and 6 cases of periprosthetic fracture in the AAS group. There was no significant difference in the incidence of complications between the two groups (P>0.05). At last follow-up, the BASDAI, BASFI, SF-12 MCS, SF-12 PCS, and HHS score of the two groups were significantly improved when compared with those before operation (P<0.05); but there was no significan difference in the difference of the above parameters before and after operation and the patient satisfaction between the two groups (P>0.05). Conclusion The midterm follow-up outcomes of THA for the treatment of JAS patients were reliable. A low age at disease onset did not exert a significant negative effect on THA reconstruction for the treatment of ankylosing spondylitis.
ObjectiveTo systematically review the effectiveness and safety of thalidomide for ankylosing spondylitis (AS). MethodsDatabases including Ovid MEDLINE (1946 to 2014.2.1), EMbase (1947 to 2014.2.1), CENTRAL (Issue 1, 2014), CBM (1978 to 2014.2.1), CNKI (1994 to 2014.2.1), WanFang Data (1980 to 2014.2.1) and VIP (1989 to 2014.2.1) were searched for randomized controlled trials about the effectiveness and safety of thalidomide for AS. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Meta-analysis was then conducted using RevMan 5.2 software. ResultsSeven RCTs were included involving 544 patients. The results of meta-analysis showed that, compared with the blank group, thalidomide increased clinical remission, but it showed no obvious advantage in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and secondary outcome index, with an increased total rate of withdrawal/drop-out. Compared with SSZ, thalidomide increased the rate of maintaining remission when it was used in the maintenance treatment after the patients attained ASAS20; and for other outcomes it was similar to SSZ. Compared with NSAIDs, thalidomide increased the rate of maintaining remission when it was used in the maintenance treatment after the patients attained ASAS20; it increased clinical remission; for secondary outcomes it was similar to NSAIDs; and it had a higher incidence of adverse reaction as well as an increased total rate of withdrawal/drop-out. ConclusionCompared with the blank group, thalidomide increases clinical remission, with an obviously-increased total rate of withdrawal/drop-out. Compared with SSZ, thalidomide increases the rate of maintaining remission when it is used in the maintenance treatment after patients attain ASAS20. Compared with NSAIDs, thalidomide increases the rate of maintaining remission when it is used in the maintenance treatment after patients attain ASAS20; it also increases clinical remission; but it has a higher incidence of adverse reaction as well as an increased total rate of withdrawal/drop-out. Due to limited quantity and quality of the included studies, the above conclusion needs to be verified by conducting more high quality studies.
Objective To summarize the mid- to long-term effectiveness of total hip arthroplasty (THA) in the treatment of the involved hips in patients with ankylosing spondylitis (AS), and to investigate its influencing factors. Methods Between March 1999 and May 2011, 32 patients (42 hips) with AS and involved hip underwent THA. There were 26 males and 6 females with a mean age of 39 years (range, 20-78 years). The disease duration ranged from 2 to 41 years, with a median of 10 years. Metal-on-polyethylene bearings were used in 19 hips, and ceramic-on-ceramic bearings in 23 hips. The diameter of prosthetic femoral head was 36 mm in 15 hips and was 28 mm in 27 hips; and all the prostheses were fixed biologically. The Harris score, visual analogue scale (VAS) score, and total range of motion (ROM) of the hip were compared between at pre- and post-operation to evaluate the effectiveness. The DeLee zone was used for describing acetabular prosthesis, the Gruen zone for describing femoral prosthesis, and the Brooker criterion for evaluating the heterotopic ossification. Results Healing of incision by first intention was achieved in all patients after operation. There was no complication of anesthetic accident, infection, or neurovascular injury. Twenty-nine cases (39 hips) were followed up 5-17 years (mean, 9 years). Anterior dislocation of hip joint occurred in 2 hips of 24 hips (28 mm diameter), but did not in 15 hips (36 mm diameter). At last follow-up, the Harris score, VAS score, and the total hip ROM were significantly improved (P<0.05). The shorter the disease duration was, the higher postoperative Harris score and the greater postoperative total hip ROM would be (P<0.05); the bigger diameter of prosthetic femoral head was, the greater postoperative total hip ROM would be (P<0.05). All the acetabular components and femoral stems were well fixed at last follow-up. The osteolysis rate around the acetabular cup in the metal-on-polyethylene bearing group (50%, 9/18) was higher than that in the ceramic-on-ceramic bearing group (0, 0/21). No prosthetic loosening was observed in 2 groups. Seven hips were found to have heterotopic ossification, including 5 hips of Brooker grade I and 2 hips of Brooker grade II. Conclusion THA is an effective method to treat involved hips in patients with AS; especially for patients having shorter duration of the disease, THA shows better effectiveness when the bigger diameter of prosthetic femoral head and ceramic-on-ceramic bearing are used.
ObjectivesTo systematically review the proportion of Tregs in peripheral blood of patients with ankylosing spondylitis (AS) and its relationship with Treg's diffrent phenotypes.MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect case-control studies on peripheral Tregs of AS patients from inception to November 31st, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 61 case-control studies involving 2 466 AS patients and 1 879 controls were included. The results of meta-analysis showed that: the proportion of peripheral Tregs of patients with AS was significantly lower than that of the normal control (SMD=−0.905, 95%CI −1.294 to −0.517, P<0.000 1), and the proportion of Tregs in the disease-active group was significantly lower than that in disease-inactive group (SMD=−0.928, 95%CI −1.431 to −0.425, P<0.000 1). The proportion of CD4+CD25+FOXP3+Tregs and CD4+CD25+CD127low/−Tregs were lower in AS patients than that in control subjects (SMD=−2.547, 95%CI −3.521 to −1.573, P<0.000 1; SMD=−0.709, 95% CI −1.056 to −0.362, P<0.000 1). The proportion of Tregs defined by CD4+CD25low/−FOXP3+ was higher in AS patients (SMD=0.683, 95%CI 0.161 to 1.206, P=0.01). There was no significant difference betweew other phenotypes of Tregs groups.roups.ConclusionsThe reduction of Tregs may be one of the important reasons for the occurrence and development of AS, which may provide a new approach for the diagnosis and treatment of AS.
Objective To explore the characteristics and the related factors of the lipid profiles in patients with ankylosing spondylitis (AS). Methods Sixty AS patients and 60 healthy controls were included retrospectively from January 2005 to January 2015. Information including general data, physical examination, and blood sample were collected; triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), and C-reactive protein (CRP) were assessed. Results TG increased in 46.7% (28/60) patients, and HDL-C decreased in 50.0% (30/60). Compared with the control group, AS patients had lower levels of HDL-C, TC and LDL-C, and higher levels of TG, VLDL-C, VLDL-C/LDL-C ratio, LDL-C/HDL-C ratio, and TC/HDL-C ratio; the differences above were all statistically significant (P<0.01). Spearman correlation test demonstrated that HDL-C level was correlated negatively with serum CRP (rs=–0.359, P=0.005). Multiple linear regression model demonstrated that CRP was associated with HDL-C in AS patients (P=0.019). Conclusions Dyslipoproteinemia is a common feature in AS patients. The main characteristic is the increase of TG and decrease of HDL-C, related with inflammation. It suggests a high risk of atherosclerosis.
Therapeutic drug monitoring (TDM) has been more widely used in small molecule agents, such as immuno-suppressants, antiepileptic drugs and antibiotics, with less attention in the field of therapeutic biological agents. Monoclonal drugs represented by tumor necrosis factor alpha (TNF-α) inhibitors have shown a good relationship between exposure and efficacy in clinical studies. There are corresponding guidelines and consensus for the recommendations of TDM based on current research evidence. Therefore, this paper introduced the current evidence, strategies and considerations for TDM in the optimal treatment of adalimumab from the perspective of adalimumab TDM to provide references for the clinical practice of adalimumab TDM.