Optimum duration of antithyroid drug treatment determined by assay of thyroid stimulating antibody in patients with Graves' disease.

OBJECTIVE--To determine the optimal duration of antithyroid drug treatment by monitoring serum thyroid stimulating antibody values in patients with Graves'' disease. DESIGN--Prospective longitudinal trial of patients with Graves'' disease followed up for 24 months after withdrawal of treatment. SETTING--Tertiary referral centre. PATIENTS--A total of 64 consecutive patients with untreated Graves'' disease, eight of whom were subsequently excluded. Fifty six patients completed the study. INTERVENTIONS--All patients were treated initially with carbimazole 40 mg, then with decreasing doses that maintained a euthyroid state. Treatment was scheduled to continue for 18 months but was withdrawn earlier if serum thyroid stimulating antibody became undetectable. END POINT--Serum values of thyroid stimulating antibody (assayed by stimulation of human thyroid cells in vitro) and thyroid hormones and thyroid state every three months during treatment and afterwards every six months for 24 months. MEASUREMENTS AND MAIN RESULTS--In 44 patients serum thyroid stimulating antibody became undetectable during treatment and treatment was withdrawn (median duration of treatment nine months, range 3-18 months). In 12 patients the antibody could be detected during 18 months of treatment. Among the first group of 44 patients initial values of the antibody before treatment were significantly lower than in the second group of 12 patients (median 225% (range 138-1236%) v 570% (250-1480%), p less than 0.001); the incidence of relapse was also lower (41% v 92%, p less than 0.001); and among those who did relapse the disease free interval after treatment was longer (median 12 months v 1 month, p less than 0.001). Moreover, the initial median serum values of thyroid stimulating antibodies were not related to the occurrence of relapse or remission as these did not differ between patients who did and did not have a relapse (median 267% (range 139-1480%) v 220% (range 138-1236%). CONCLUSION--Monitoring of serum thyroid stimulating antibody was a good guide to the duration of treatment as it allowed the treatment period to be considerably shortened in a large group of patients with no loss of efficiency.     

Expectations of assisted conception for infertility.

OBJECTIVE--To provide reliable prognostic information for couples seeking assisted conception. DESIGN--Analysis of four years'' practice (1988-91). SETTING--Private university service linked with NHS reproductive medicine services. PATIENTS--804 couples with various causes of subfertility, median duration five years, median age of women 34 years. INTERVENTIONS--1280 completed cycles: 950 in vitro fertilisation, 144 gamete intrafallopian transfer, and 186 intrauterine insemination and superovulation. MAIN OUTCOME MEASURES--Pregnancy and birth rates per cycle and cumulative pregnancy and take home baby rates per couple. RESULTS--In women under 40 years and men with normal sperm, whatever the cause of infertility, results with in vitro fertilisation improved steadily reaching a pregnancy rate per cycle of 30% (95% confidence interval 26% to 35%) during 1990-1 and birth rate per cycle of 29% (23% to 35%) in 1990. Pregnancy and birth rates for gamete intrafallopian transfer were 36% (28% to 44%) and 26% (17% to 37%) and for intrauterine insemination 18% (12% to 24%) and 16% (10% to 22%). After six cycles cumulative probability of pregnancy was 82% and cumulative take home baby rate 70%. Considering only in vitro fertilisation and gamete intrafallopian transfer after four cycles the pregnancy rate was 78% (66% to 91%). CONCLUSIONS--Conception is less likely in women over 40 and men with sperm dysfunction. For other couples the prognosis for a live birth is at least as good as for fertile couples if they persist with treatment.     

Exploring the use of internal and externalcontrols for assessing microarray technical performance

Background

Anthroposophic medicine is a physician-provided complementary therapy system involving counselling, artistic and physical therapies, and special medications. The purpose of this analysis was to identify predictors of symptom improvement in patients receiving anthroposophic treatment for chronic diseases.

Methods

913 adult outpatients from Germany participated in a prospective cohort study. Patients were starting anthroposophic treatment for mental (30.4% of patients, n = 278/913), musculoskeletal (20.2%), neurological (7.6%), genitourinary (7.4%) or respiratory disorders (7.2%) or other chronic indications. Stepwise multiple linear regression analysis was performed with the improvement of Symptom Score (patients' assessment, 0: not present, 10: worst possible) after 6 and 12 months as dependent variables. 61 independent variables pertaining to socio-demographics, life style, disease status, co-morbidity, health status (SF-36), depression, and therapy factors were analysed.

Results

Compared to baseline, Symptom Score improved by average 2.53 points (95% confidence interval 2.39-2.68, p < 0.001) after six months and by 2.49 points (2.32-2.65, p < 0.001) after 12 months. The strongest predictor for improvement after six months was baseline Symptom Score, which alone accounted for 25% of the variance (total model 32%). Improvement after six months was also positively predicted by better physical function, better general health, shorter disease duration, higher education level, a diagnosis of respiratory disorders, and by a higher therapy goal documented by the physician at baseline; and negatively predicted by the number of physiotherapy sessions in the pre-study year and by a diagnosis of genitourinary disorders. Seven of these nine variables (not the two diagnoses) also predicted improvement after 12 months. When repeating the 0-6 month analysis on two random subsamples of the original sample, three variables (baseline Symptom Score, physical function, general health) remained significant predictors in both analyses, and three further variables (education level, respiratory disorders, therapy goal) were significant in one analysis.

Conclusion

In adult outpatients receiving anthroposophic treatment for chronic diseases, symptom improvement after 6 and 12 months was predicted by baseline symptoms, health status, disease duration, education, and therapy goal. Other variables were not associated with the outcome. This secondary predictor analysis of data from a pre-post study does not allow for causal conclusions; the results are hypothesis generating and need verification in subsequent studies.     

Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden

The objective of this work is to compare the adherence to therapy of patients receiving etanercept and infliximab during first tumour necrosis factor (TNF)-blocking treatment course in rheumatoid arthritis. Special emphasis is placed on potential predictors for treatment termination and the impact of concomitant methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). Patients (n = 1,161) with active rheumatoid arthritis, not responding to at least two DMARDs including MTX starting etanercept or infliximab therapy for the first time, were included in a structured clinical follow-up protocol. Information on diagnosis, disease duration, previous and ongoing DMARDs, treatment start and termination, as well as cause of withdrawal was prospectively collected during the period of March 1999 through December 2004. Patients were divided into six groups according to TNF-blocking drugs and concomitant DMARDs. Five-year level (one-year) of adherence to therapy was 36% (69%) for patients receiving infliximab in combination with MTX compared with 65% (89%) for patients treated with etanercept and MTX (p < 0.001). Cox regression models showed that the risk for premature treatment termination of patients treated with infliximab was threefold higher than for etanercept (p < 0.001). Also, the regression analysis showed that patients receiving concomitant MTX had better treatment continuation than patients treated solely with TNF blockers (p < 0.001). Moreover, patients receiving concomitant MTX had superior drug survival than patients receiving other concomitant DMARDs (p < 0.010). The superior effect of MTX was associated primarily with fewer treatment terminations because of adverse events. In addition, the study identifies low C-reactive protein level, high age, elevated health assessment questionnaire score, and higher previous number of DMARDs as predictors of premature treatment termination. In summary, treatment with etanercept has higher adherence to therapy than treatment with infliximab. Concomitant MTX is associated with improved treatment continuation of biologics when compared with both TNF blockers as monotherapy and TNF blockers combined with other DMARDs.     

Incidence and duration of lactation and lactational performance among mothers of low-birth-weight and term infants.

The lactation experience of 55 mothers of 62 infants of low birth weight (2500 g or less) was prospectively compared with that of 55 mothers of 55 control infants (38 weeks'' gestation or more, birth weight more than 2500 g) born at the same institution. The incidence rates of lactation at delivery were 73% for the control group and 58% for the low-birth-weight group; 11% of the infants of low birth weight fed breast milk were never put to the breast. The mean age at first suckling was 277.3 hours in the low-birth-weight group, compared with 3.3 hours in the control group (p less than 0.0005). At first suckling 81% of the low-birth-weight infants and 25% of the control infants sucked poorly or refused the breast (p less than 0.001). At discharge 65% of the breast-milk-fed control infants were exclusively breast-fed, compared with 3% of the low-birth-weight infants fed breast milk (p less than 0.001). The incidence rates of lactation over time were similar in the control and low-birth-weight groups (51% v. 44% at 1 month, 29% v. 13% at 3 months, 13% v. 4% at 6 months and 4% v. 2% at 12 months). The mean duration of lactation was 3.2 months for the control group and 2.5 months for the low-birth-weight group. In the long term 37% of the low-birth-weight infants fed breast milk failed to breast-feed, compared with 2% of the control infants, and only 31% were exclusively breast-fed, compared with 85% of the control infants (p less than 0.001). However, the degree of satisfaction with the lactation experience was similar in the two groups. We conclude that mothers of low-birth-weight infants have good potential for lactation.     

宫腔镜联合腹腔镜在女性不孕症诊治中的应用

摘要目的：探讨宫腔镜联合腹腔镜在女性不孕诊断及治疗中的临床应用价值。方法：回顾性分析60 例我院收治的采用宫腔镜联 合腹腔镜进行诊断和治疗的女性不孕症患者为研究对象,对其临床资料进行分析。结果：宫腔镜联合腹腔镜检查发现,60 例不孕 症患者中,56.7 %的患者患有慢性盆腔炎,16.7 %的患者为子宫内膜异位症,11.7 %的患者为多囊卵巢综合征;单纯腹腔镜检查的 阳性检出率为60.0 %,单纯宫腔镜检查的阳性检出率为28.3 %,宫腔镜联合腹腔镜检查的阳性检出率高达91.7 %,宫腔镜联合腹 腔镜镜检阳性发现率明显高于前二者(P < 0.05)。治疗前,双侧不通、一侧通畅和双侧输卵管通畅的患者分别为38.3 %、48.3 %和 13.3 %,经宫腔镜联合腹腔镜治疗后分别为11.7 %、50.0 %和38.3 %,差异均有统计学意义(P<0.05)。34 例原发性不孕患者,术后 13例妊娠,妊娠率38.2 %;26 例继发性不孕患者,术后15 例妊娠,妊娠率57.7 %;总妊娠率为46.7 %,其中宫外孕2例。结论：宫 腔镜联合腹腔镜检查可帮助明确女性不孕症患者明确原因及发病部位,并可针对病因进行治疗,提高女性不孕症的病因诊断准 确率及治愈率。     

Heat stress-induced alterations in the synthesis and secretion of proteins and prostaglandins by cultured bovine conceptuses and uterine endometrium

Effect of in vitro heat stress on protein and prostaglandin synthesis and secretion by bovine conceptuses and endometrium was examined. Conceptuses (n = 11) and endometrium (n = 10) obtained on Day 17 of pregnancy were cultured at thermoneutral (39 degrees C, 24 h) or heat stress (39 degrees C, 6 h; 43 degrees C, 18 h) temperatures in medium supplemented with L-[4,5-3H]leucine (100 microCi) and arachidonic acid (10 micrograms/ml). Radiolabeled protein secreted into culture medium increased with time in both groups. Heat stress reduced (p less than 0.001) incorporation of [3H]leucine into intracellular and secreted proteins by conceptuses but did not alter incorporation of [3H]leucine by endometrium. In particular, heat stress reduced by 72% the secretion of bovine trophoblast protein-1, the conceptus polypeptide believed to cause extension of luteal lifespan. Two-dimensional, sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that heat stress altered the array of proteins in endometrial and conceptus tissues, as evidenced by the induction of "heat-shock proteins." Endometrial secretion of prostaglandin F (p less than 0.001) and conceptus secretion of prostaglandin E2 (p less than 0.05) increased in response to heat stress. Sensitivity of bovine conceptuses and endometrium to heat stress in vitro suggests that infertility associated with maternal heat stress may be caused, partially by alterations in signals required for maintenance of the corpus luteum during early pregnancy.     

Evaluation of intra-uterine contraception in selected mission hospitals in India

The follow-up records of the 4067 women accepting Lippes loops (27.5 and 30 mm) during 1967-1968 in 15 randomly selected member mission hospitals of the Family Planning Project of the Christian Medical Association of India were studied. 97.7% of the insertions were not postpartum. Median age was 29.8. The difference between the mean number of living children, 3.7, and the mean parity, 4.9, suggests that a relatively high rate of infant and child mortality is characteristic of IUD acceptors. Analysis of the responses of 1656 acceptors to 1 query showed attitude toward the loop was favorable by both husband and wife in 77.3% of these cases and by either husband or wife in 90.5% of these cases. Expulsions, removals, and pregnancies were unaffected in any significant way by age. Expulsion, removal, and pregnancy rates were higher, but nonsignificantly so, for the 27.5 mm than for the 30 mm loop. The 27.5 mm loop was associated with a significantly higher proportion (p less than .05) of prolonged and heavy bleeding than was the 30 mm loop. The average number of women months of use was 6.7 (very low in a follow-up study of 24 months) and more or less unrelated to age. Most removals were due to bleeding, symptoms associated with bleeding, or desire for planned pregnancy. Removal rate was more or less uniform for all parities. With increase in the duration of use up to 18 months the complaint rate appeared to decrease, but after 18 months it appeared to increase again suggesting that IUDs cause irritation of the endometrium after long periods of use. Women less than age 25 had a significantly greater (p less than .01) percentage of reinsertion than did women age 25 or greater. The cumulative net termination rate after 24 months was 53.9 (plus or minus 1.4) per 100 first insertions, a rate comparing well with similar Indian figures. Pregnancy rate was 2 per 100 first insertions. Of the 2 devices the 30 mm loop seems the more effective and ideally suited for fertility control.     

Prevalence of primary infertility in China: in-depth analysis of infertility differentials in three minority province/autonomous regions

Following the 1994 UN International Conference on Population and Development, there was a shift in emphasis on women's reproductive health and there emerged a need for more knowledge about levels and differentials of infertility. Using the data from the 1988 National Two-Per-Thousand Sample Survey on Fertility and Contraception, this paper estimated the prevalence of primary infertility in China. To determine the predictors of primary infertility, multiple logistic regression analyses were done on three minority province/autonomous regions where primary infertility was the highest. A non-contracepting, sexually active woman was considered to have primary infertility if she had not reported a recognized pregnancy after at least seven years of marriage. The analysis shows that the national level of primary infertility was relatively low (1.3%). Primary infertility was higher in Qinghai (2.3%), Tibet (3.7%) and Xinjiang (3.7%) compared with other provinces. Tibetans in Qinghai and Uygurs in Xinjiang had a higher level of primary infertility than the Han Chinese. Ethnic differences remained after adjusting for other background characteristics. Divorced and remarried women had significantly higher odds of primary infertility compared with first-married women in Qinghai and Xinjiang. The elevated level of primary infertility in Qinghai, Tibet and Xinjiang and its disproportionate prevalence among Tibetans and Uygurs highlight the need for further work to understand the causes and social consequences of infertility for the minority population in China.     

Chronic otitis media with effusion (glue ear) and adenotonsillectomy: prospective randomised controlled study.

A prospective study was conducted of the effects of adenoidectomy and adenotonsillectomy on established otitis media with effusion unresponsive to medical treatment. The operations were performed at random with a controlled no surgery group on a cohort of 103 children with the condition and the results assessed six weeks, three months, six months, nine months, and one year later. After adenoidectomy the rate of resolution of the condition increased from 39% at six weeks to 72% at one year; and after adenotonsillectomy the rate increased from 59% at six weeks to 62% at one year. In the no surgery group the rate increased from 16% at six weeks to 26% at one year. Compared with the no surgery group the effect of adenoidectomy alone at one year was highly significant (p less than 0.001), and similarly the effect of adenotonsillectomy was significant (p less than 0.01). There was, however, no increased benefit from the addition of tonsillectomy compared with adenoidectomy alone. Thus there was resolution of 36-46% of chronic effusions as a result of adenoidectomy.     

Interpretation of semen analysis among infertile couples.

Among the male partners of 1074 infertile couples the mean results of semen analysis were sperm count 78 X 10(6)/ml, seminal volume 4.0 ml, proportion of progressively motile sperm 54%, proportion of sperm with normal morphologic features 81.4% and total motile sperm count 152.3 X 10(6) per ejaculate. After excluding 65 couples who chose donor insemination and 300 with known female causes of infertility, the cumulative pregnancy rates in the remaining 709 couples were higher with increasing sperm density and motility and seminal volume, but the higher rates were significant only when these variables were combined into total motile sperm count per ejaculate. The cumulative pregnancy rates were 20% with a total motile sperm count of 9 X 10(6) or less, 37% with a count of 10 to 19 X 10(6) and 52% with a count of 20 X 10(6) or more (p = 0.001). Counts higher than 20 X 10(6) were not associated with a further improvement in pregnancy rates, but variability in the results was high, which suggests that the test should be repeated as necessary to determine the true range. Although standards for these and other seminal variables are ill defined, the total motile sperm count incorporates the most useful prognostic information from semen analysis, and the associated pregnancy rates can help guide clinical decisions.     

Prediction of recurrence in incompletely excised basal cell carcinoma

This 5-year prospective study evaluated histologic criteria as predictors of tumor recurrence for the individual with a "positive-margin" basal cell carcinoma. The results demonstrated that 93 percent of patients with greater than 75 percent of their tumor cords containing irregularities in in the peripheral palisade had tumor recurrence, while no patient with less than 25 percent of their tumor cords containing irregularities in the peripheral palisade developed a recurrence in 5 years of follow-up. After statistical analysis for the other histologic variables, the presence of greater than 75 percent irregularities in the peripheral palisade conferred a 39-fold increased risk of tumor recurrence, significant at the p much less than 0.001 level. For the patient in the intermediate group (25 to 75 percent irregularities in the peripheral palisade), the presence of a weak host response (absent to minimal infiltration of small lymphocytes) increased the risk of tumor recurrence fourfold, with this effect being significant at the p less than 0.05 level. The presence of tumor ulceration conferred a 2.8-fold increased risk for tumor recurrence, significant at the p less than 0.01 level, while the presence of squamous differentiation conferred no increased risk. This study may provide a valid basis for predicting tumor recurrence in the individual with a positive-margin basal cell carcinoma.     

Marriage season, promptness of successful pregnancy and first-born sex ratio in a historical natural fertility population – evidence for sex-dependent early pregnancy loss?

 We investigated population-based vital records of the seventeenth and eighteenth century French Canadian population to assess the effects of marriage season on the outcome of the first births under natural fertility conditions (n=21,698 marriages). Promptness of the first successful conception after marriage differed according to marriage season; the proportion of marriages with a marriage-first birth interval of 8.0–10.0 months was lowest (34%) for marriages in August–October (P=0.001). Although the male/female sex ratio of the babies born with an interval of 8.0–10.0 months was generally higher (1.10) than those with an interval of 10.0–24.0 months (1.05), the marriages in August–October resulted in a significantly reduced sex ratio (0.96) among only the prompt conceptions (P=0.026). We discuss whether this seasonal reduction of the sex ratio could be partly explained by a clustered pregnancy loss of male zygotes in early pregnancy. Received: 5 January 1998 / Accepted: 9 September 1998     

The effect of gender and age on growth hormone replacement in growth hormone-deficient patients.

We analyzed the effect of growth hormone replacement therapy (36 months) analyzed at a dose adjusted to maintain serum insulin-like growth factor-I level between the median and the upper end of the age-related reference range on bone mineral density, body composition, and carbohydrate metabolism with respect to gender and age in 20 adult patients (9 women, 11 men, mean age: 43 years, range: 21-61 years). The lumbar and femoral T-score was increased after 12 and after 18 months of therapy respectively in men (p < 0.001 and p = 0.002), but did not changed significantly in women. The increase of femoral T-score was greater in young men (< or = 45 years, n = 6) than old men (> 45 years, n = 5, p < 0.001). Body fat was lower in men than in women after 6 months (p = 0.002). The waist/hip ratio only decreased in women (p = 0.044). The waist circumference decreased in both genders after 6 months of therapy (p < 0.001), but more markedly in females than in males (p < 0.05). The sum of skinfold thicknesses was reduced in males after 6 months of therapy (p < 0.001). Changes in body composition parameters measured were independent of age. The glycosylated hemoglobin increased without sex or age difference after 12 months of initiation of therapy (p < 0.001), but fasting glucose and insulin levels did not change during the therapy. Our results indicate that the effect of growth hormone replacement on bone mineral content in adults is age- and gender-dependent, gender dependent on body composition, but independent of age and gender on carbohydrate metabolism.     

Increase in urinary thromboxane excretion during pregnancy and labor

Urinary TXB2 excretion was measured during pregnancy and labor using high pressure liquid chromatography and radioimmunoassay. From the first trimester onwards TXB2 levels in urine of pregnant women (n = 60) were significantly (p less than 0.001) higher than in non-pregnant women (n = 12) and they increased, albeit not significantly, with advancing gestation. Labor was associated with a two-fold increase in urinary TXB2 excretion. Levels in established labor were significantly higher than at any other time in pregnancy (p less than 0.001), but the levels in incipient labor showed considerable overlap with these in late pregnancy. Thus urinary TXB2, while not necessarily originating from the pregnant uterus, appears to reflect the uterine activity of labor and may be the expression of a general stimulation of prostanoid production during parturition.     

Cervical diameter after suction termination of pregnancy.

The diameter of the internal cervical os was measured in several groups of patients in an attempt to assess any damage caused by suction termination of pregnancy. Pregnant women who had had a previous abortion by vacuum aspiration had significantly greater cervical diameters than those who had not, and there was a statistically significant correlation between dilatation of the cervix at operation and cervical diameter at six weeks'' follow-up. Cervical dilatation to 10 mm or less was subsequently associated with a normal cervical diameter, but the diameter was often large when the extent of dilatation was greater than 12 mm or not known. Cervical dilatation at termination of pregnancy should, if possible not exceed 10 mm.     

Occupational Health Practice

The working status of 1165 patients aged 59 years or less (mean 49.8 years) was evaluated 7 to 77 months (mean 36 months) after aortocoronary bypass surgery. Although 76% of the patients eventually returned to work, only 56% were working 6 months after their operation. The proportion of patients working peaked at 2 years after the operation (at 66%) and decreased progressively to 56% at 4 years and 53% at 5 years without ever reaching the proportions that applied 12 and 6 months before the operation (84% and 69% respectively). Multivariate analysis identified three socioeconomic and three clinical variables as predicting the working status at 6 months and at yearly points during the first 4 years after the operation. Of the socioeconomic variables analysed, preoperative unemployment of long duration, a preoperative occupation that required strenuous physical effort and a low level of education were, in that order, the strongest predictors of postoperative unemployment. Among the clinical variables, associated noncardiovascular illness and the severity and duration of angina pectoris independently influenced the patients'' post-operative working status. The authors conclude that modification of some of these variables should by attempted both before and after aortocoronary bypass surgery to see whether the rate of return to employment after the operation can be improved in selected patients.     

椎间孔镜与开窗术对腰椎间盘突出患者远期治疗效果对比

目的:探究椎间孔镜与开窗术对腰椎间盘突出患者治疗远期效果对比。方法:选择2016年3月至2018年3月于我院接受治疗的腰椎间盘突出患者,按照其接受术式的不同将其分为孔镜组(108例)和开窗组(40例),对比两组手术出血量、术后卧床时间及切口长度,对比两组术前、术后3个月及术后12个月腰椎日本矫形外科学会(Japan Orthopaedic Assoctiation,JOA)评分、Odwestry功能障碍指数(Odwestris ability index, ODI)评分、视觉模拟评分(Visual analog scales,VAS)及生活质量评分,最后对比两组术后12个月椎间隙高度降低数值。结果:(1)孔镜组术中出血量、术后卧床时间及切口长度均小于开窗组,手术时间长于开窗组(P0.05);(2)术前两者JOA及ODI评分对比无统计学意义(P0.05),术后3个月及术后12个月孔镜组JOA及ODI评分优于开窗组(P0.05);(3)术前两组VAS及SF-36量表(the 36-item shot form health survey,SF-36)评分对比无统计学意义(P0.05),术后3个月及12个月两组VAS评分均有明显下降,SF-36评分有明显上升(P0.05),且术后3个月及12个月孔镜组SF-36评分高于开窗组(P0.05),VAS评分对比无统计学意义(P0.05);(4)术后12个月,孔镜组椎间隙高度降低率低于开窗组(P0.05)。结论:椎间孔镜在治疗腰椎间盘突出方面效果较好,相比于开窗术,孔镜术患者术中创伤小、术后恢复快、腰椎功能改善明显,且远期随访显示患者生活质量更高,值得进行临床推广。     

Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden

The objective of this work is to compare the adherence to therapy of patients receiving etanercept and infliximab during first tumour necrosis factor (TNF)-blocking treatment course in rheumatoid arthritis. Special emphasis is placed on potential predictors for treatment termination and the impact of concomitant methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). Patients (n = 1,161) with active rheumatoid arthritis, not responding to at least two DMARDs including MTX starting etanercept or infliximab therapy for the first time, were included in a structured clinical follow-up protocol. Information on diagnosis, disease duration, previous and ongoing DMARDs, treatment start and termination, as well as cause of withdrawal was prospectively collected during the period of March 1999 through December 2004. Patients were divided into six groups according to TNF-blocking drugs and concomitant DMARDs. Five-year level (one-year) of adherence to therapy was 36% (69%) for patients receiving infliximab in combination with MTX compared with 65% (89%) for patients treated with etanercept and MTX (p < 0.001). Cox regression models showed that the risk for premature treatment termination of patients treated with infliximab was threefold higher than for etanercept (p < 0.001). Also, the regression analysis showed that patients receiving concomitant MTX had better treatment continuation than patients treated solely with TNF blockers (p < 0.001). Moreover, patients receiving concomitant MTX had superior drug survival than patients receiving other concomitant DMARDs (p < 0.010). The superior effect of MTX was associated primarily with fewer treatment terminations because of adverse events. In addition, the study identifies low C-reactive protein level, high age, elevated health assessment questionnaire score, and higher previous number of DMARDs as predictors of premature treatment termination. In summary, treatment with etanercept has higher adherence to therapy than treatment with infliximab. Concomitant MTX is associated with improved treatment continuation of biologics when compared with both TNF blockers as monotherapy and TNF blockers combined with other DMARDs.