Minimal clinically important difference for acupuncture for patients with chronic spontaneous urticaria: secondary analysis from a multicentre randomised controlled trial in China

Abstract

Objectives

To evaluate the minimal clinically important difference (MCID) value for acupuncture treatment in chronic spontaneous urticaria (CSU), providing guidance for its application in CSU management.

Design

Secondary analysis of data from a multicentre randomised controlled trial.

Setting

Three tertiary hospitals across three cities in China.

Participants

103 CSU patients (78.7% female) with an average age of 39.97 years.

Interventions

Participants received acupuncture treatment for 4 weeks in the original study.

Outcome measures

MCID and minimal detectable change (MDC) for the Urticaria Activity Score over 7 days (UAS7) in acupuncture treatment of CSU. Convergent validity assessed by intraclass correlation coefficient (ICC). Responsiveness evaluated through Spearman correlation between UAS7 improvements and anchor tools (physician’s and patient’s assessments). MDC calculated using SE of measurement of changes in UAS7 scores. MCID estimated using distribution-based and anchor-based methods.

Results

The ICC for UAS7 was 0.86. Improvements in UAS7 scores were significantly correlated with patient (r=0.44, p<0.01) and physician (r=0.85, p<0.01) assessments of CSU activity shifts. The MDC for UAS7 was 5.08. The MCID for acupuncture treatment in CSU was 8.3.

Conclusions

This study provides the first MCID value for acupuncture treatment in CSU. These findings contribute to the understanding of acupuncture’s effects in treating CSU and may inform future research and clinical practice in the management of this condition.

Trial registration number

ChiCTR1900022994.

Correspondence to Dr Yunzhou Shi; [email protected]

Strengths and limitations of this study

• This study employed both distribution-based and anchor-based methods to determine the minimal clinically important difference (MCID) for the Urticaria Activity Score over 7 days.

• Multiple statistical approaches, including intraclass correlation coefficient and Spearman correlation, were used to assess validity and responsiveness, strengthening the robustness of the findings.

• Both distribution-based and anchor-based methods for determining MCID have inherent considerations, with the former potentially not directly reflecting individual patient experiences and the latter being influenced by anchor selection.

• The relatively small sample size (n=103) may limit the precision of our estimates.

Background

Chronic spontaneous urticaria (CSU) stands as one of the most prevalent dermatological conditions. It is distinguished by the presence of hives, with or without angioedema, persisting for more than 6 weeks without an obvious trigger.¹ With a lifetime incidence rate of 1.4% within the general population,² CSU predominantly affects women and imposes a substantial burden on both patients and their families, as well as on healthcare systems.³ Current guidelines predominantly endorse the use of second-generation antihistamines (SgAH), omalizumab and cyclosporine as treatment options.¹ Each treatment has its own risk-benefit profile and requires careful customisation.⁴ Recent guidelines emphasise that the foremost treatment objective in managing CSU is to ensure patients achieve complete control over their condition.¹ However, existing pharmacological interventions may not fully cater to all patients’ needs.⁴ Given these limitations, emerging therapeutic interventions and strategies are being explored.⁵ Notably, recent guidelines now emphasise non-pharmacological therapies in managing this condition.¹ This shift highlights the need for more holistic and personalised treatment approaches. Hence, investigating effective non-pharmacological approaches is crucial not only for diversifying the comprehensive management of CSU but also for catering to patients who respond poorly to or are intolerant of conventional drug therapies.

Acupuncture, a complementary and alternative medical practice, has a longstanding history in China for treating urticaria. Systematic reviews⁶ and our previous study⁷ indicate its potential effectiveness in alleviating CSU symptoms. However, assessing the clinical efficacy of acupuncture for CSU remains challenging due to the lack of convincing standards. The minimal clinically important difference (MCID) plays a crucial role in sample size estimation and clinical decision-making and can be used as an important reference for clinical significance assessment.⁸ Existing studies^9–11 have calculated MCID for CSU based on pharmacological treatments. It is essential to recognise that the determination of MCID can vary depending on the specific treatment methods.¹² Applying these pharmacologically derived MCID values directly to evaluate the clinical effectiveness of acupuncture is not reliable.¹³ Therefore, conducting a dedicated study to determine the MCID for acupuncture in CSU treatment is of paramount importance. This will not only serve as a crucial benchmark for measuring acupuncture’s effectiveness but also as a valuable reference for evaluating other non-pharmacological interventions.

Methods

Patient group

This research used data from a multicentre randomised controlled trial focusing on acupuncture treatment for CSU.⁷ It included a total of 110 patients aged between 18 and 70, all of whom had been diagnosed with CSU at least 2 months prior to the study. Over 4 weeks, these participants received 16 sessions of acupuncture. The study’s protocol and treatment specifics are detailed in a previous publication.⁷ The analysis was carried out on a subset of 103 patients who completed the treatment without imputing missing data.

Assessment tools

The Urticaria Activity Score (UAS) is a validated, globally recognised patient-reported outcome measure for assessing the severity of CSU symptoms.⁹ The Urticaria Activity Score over 7 days (UAS7), a common application of UAS, aggregates daily hive count and itch intensity over 7 days (range 0–42), with higher scores indicating more active disease.¹ Current urticaria guidelines recommend UAS7 for monitoring disease activity and assessing treatment responses in CSU patients.⁴

Study design

Patients were instructed to record their disease activity using UAS7 during the week before the acupuncture treatment (baseline), as well as in the second and fourth weeks following treatment initiation. Additionally, both patients and physicians conducted overall assessments of treatment effectiveness. At the end of the 4-week treatment, patients assessed (PatGA) the effectiveness of acupuncture using a 4-point Likert scale, with categories including ‘Significant Improvement’ (symptom improvement over 75%), ‘Moderate Improvement’ (50% to 75% improvement), ‘Slight Improvement’ (25% to 50% improvement) and ‘No Change’ (less than 25% improvement). Physicians’ assessments (PhyGA) classified disease severity based on an urticaria severity scale,^{14 15} categorising patients at baseline and after 4 weeks of treatment into ‘Complete Remission’ (UAS7 score=0), ‘Well Controlled’ (UAS7 score=1–6), ‘Mild Activity’ (UAS7 score=7–15), ‘Moderate Activity’ (UAS7 score=16–27) and ‘Severe Activity’ (UAS7 score=28–42). A treatment was considered effective if there was at least a one-degree improvement in disease severity after 4 weeks of acupuncture treatment.

Convergent validity and responsiveness analysis

The study assessed test-retest reliability by calculating the intraclass correlation coefficient (ICC) for patients whose urticarial symptoms were deemed unchanged from baseline according to PhyGA at the second study visit.¹⁶ Additionally, the study analysed responsiveness by assessing the Spearman correlation between the improvement in UAS7 scores after 4 weeks of acupuncture treatment and the two anchor tools (PhyGA and PatGA), respectively.

Identification of MDC

The minimal detectable change (MDC) quantifies the smallest change in a scale not attributed to random error. MDC calculation is based on the SE of measurement (SEM), which is computed as SD * √ (1 − reliability coefficient), with SD being the SD of UAS7 changes over the first 2 weeks. In this study, the ICC is used as the test-retest reliability coefficient. The formula for MDC is 1.96 * √2 * SEM.¹⁰ The MDC threshold is established at this calculated value. A change in score exceeding the MDC suggests a genuine change beyond just random error.

Establishment of MCID

The MCID represents the smallest change in a clinical setting that is considered significant. This study used both distribution-based and anchor-based methods to establish MCID. Two distributional methods were included: one using the baseline UAS7 SD multiplied by 0.5^{9 11} and the other based on the SEM of UAS7 improvement.¹¹ Additionally, an anchor-based ‘mean change’ method was employed, with patient and physician overall assessments (PatGA and PhyGA) as anchors, respectively.⁹ In the PatGA analysis, the MCID values of UAS7 were reported using the anchor points ‘significant improvement,’ ‘moderate improvement’ and ‘slight improvement,’ respectively. In the PhyGA analysis, the MCID values of UAS7 were reported separately based on the different degrees of improvement in disease activity as anchor points.¹⁷ To estimate the 95% CIs for the MCID values, a bootstrap method was employed. The procedure involved 1000 bootstrap resamples with replacement, executed using the ‘boot’ package in R. For each resample, the corresponding MCID value was calculated. The 2.5th and 97.5th percentiles of the distribution of these 1000 MCID estimates were then used to determine the 95% CI (see online supplemental table S1).

Results

Clinical characteristics

The study focused on the effects of acupuncture on CSU patients. It initially included 110 patients, predominantly females (77.3%). The average age of the participants was 38.4 (±12.81) years, and they had been suffering from CSU for an average duration of 50.05 (±62.13) weeks since their diagnosis. At baseline of the study, the mean UAS7 score was 23.5 (±9.22). Following a 4-week course of acupuncture, seven patients opted out of the study. The mean UAS7 after treatment in the remaining 103 patients decreased to 15.01 (±8.88), with an average decrease of −8.76 (±10.30). Detailed characteristics of these patients are presented in table 1. After the treatment, 43 patients (41.86%) reported significant symptom improvement, 35 patients (33.98%) reported moderate improvement and 15 patients (14.56%) experienced slight improvement. Notably, 10 patients (9.71%) observed no significant changes in their symptoms.

Table 1

Clinical characteristics of the patient population

Characteristic	Baseline (before acupuncture)	Follow-up (4 weeks after acupuncture)	Change from baseline to follow-up
No. of patients	110	103	103
Age, years	38.4±12.81	39.97±12.99
Female sex, n(%)	85 (77.3%)	80 (78.7%）
Illness duration, week	50.05±62.13	52.61±63.35
UAS7, mean±SD	23.5±9.22	15.01±8.88	−8.76±10.30
PatGA—improved disease activity
Noticeable			43 (41.8%)
Moderate			35 (33.98%)
Slight			15 (14.56%)
No change			10 (9.71%)
PhyGA—degree of improvement
3 degrees			4 (3.88%)
2 degrees			23 (22.33%)
1 degree			38 (36.89%)
No change			30 (29.13%)
Worsen			8 (7.77%)

PatGA, patients assessed; PhyGA, physicians' assessments; UAS7, Urticaria Activity Score 7 days.

Convergent validity and responsiveness analysis

The UAS7 demonstrated high test-retest reliability, with an ICC of 0.86. Furthermore, a significant correlation was observed between the post-treatment UAS7 improvement and both patient and physician overall assessments. Specifically, the Spearman correlation coefficients between UAS7 improvement and PatGA/PhyGA were 0.44 (p<0.01) and 0.85 (p<0.01), respectively, further confirming the effectiveness and sensitivity of UAS7 in evaluating treatment outcomes.

Establishing MCID

The study employed both distribution-based and anchor-based methods for estimating the MCID. In the distribution-based section, the estimated MCID values for UAS7 were 4.67 (calculated as half the SD, SD*0.5) and 3.85 (calculated as the SE, SEM). In the anchor-based section, the MCID values of UAS7 corresponding to ‘significant improvement’, ‘moderate improvement’ and ‘slight improvement’ in PatGA are 14.16, 5.77 and 5.60 respectively (see table 2). Correspondingly, 30, 65 and 65 patients achieved the respective MCID thresholds. According to PhyGA, patients who experienced improvements in disease severity by 3 degrees, 2 degrees or 1 degree had MCID values of 33.00, 16.91 and 10.82, respectively. In these groups, 2, 21 and 43 patients met the respective MCID thresholds (see table 3). In this study, the distribution-based results did not exceed the MDC threshold, while the anchor-based result was more consistent with clinical reality. Therefore, the anchor-based methods were primarily used for determining the MCID. Considering both patient (PatGA) and physician (PhyGA) assessments as equally important, the study adopted an average of the two for the final MCID determination.¹⁸ Specifically, the average of the ‘moderate improvement’ MCID in PatGA (5.77) and the ‘slight improvement’ MCID in PhyGA (10.82) was chosen, resulting in a finalised MCID of 8.30. After 4 weeks of acupuncture treatment, a total of 53 patients (51.46%) reached this MCID value (see figure 1).

Figure 1. Overview of UAS7 improvement after 4 weeks of acupuncture treatment. The red five-pointed star at the top of the figure reflects the number of people corresponding to the UAS7 improvement value. The darker the colour, the greater the number of people. UAS7, Urticaria Activity Score 7 days.

Table 2

MCID estimates based on PatGA

PatGA (no.)	MCID value (95% CI)	No. of patients meeting the MCID threshold (%)
Significant improvement (n=43)	14.16 (11.81 to 16.79)	30 (29.13%)
Moderate improvement (n=35)	5.77 (3.46 to 8.11)	65 (63.11%)
Slight improvement (n=15)	5.60 (1.07 to 10.27)	65 (63.11%)

Calculate the MCID value of UAS7 based on the mean change method.

MCID, minimal clinically important difference; PatGA, patients assessed; UAS7, Urticaria Activity Score 7 days.

Table 3

MCID estimates based on PhyGA

PhyGA (no.)	MCID value (95% CI)	No. of patients meeting the MCID threshold (%)
Improved by 3 degrees (n=4)	33.00 (25.25 to 39.50)	2 (1.94%)
Improved by 2 degrees (n=23)	16.91 (15.13 to 19.13)	21 (20.39%)
Improved by 1 degree (n=38)	10.82 (9.08 to 12.53)	43 (41.75%)

Calculate the MCID value of UAS7 based on the mean change method.

MCID, minimal clinically important difference; PhyGA, physicians' assessments; UAS7, Urticaria Activity Score 7 days.

Discussion

The establishment of the MCID is crucial for assessing the clinical significance of trial results and guiding clinical decision-making.¹⁹ The UAS7 is extensively used for assessing CSU disease activity and response to treatment.¹⁶ Although several studies^{9 20 21} have explored the MCID of UAS7 in pharmacological treatment, there is a notable absence of MCID standards for acupuncture in urticaria treatment. Systematic reviews⁶ and our previous research⁷ have already confirmed the effectiveness of acupuncture in improving CSU. This study, for the first time, provides a standard for evaluating the clinical significance of acupuncture in CSU management. These findings are instrumental in offering practical guidance for future clinical practice.

To investigate the potential influence of long-term changes in CSU activity on UAS7 scoring results, we conducted test-retest reliability analyses. The ICC obtained in this study was 0.86, aligning closely with previous studies that reported ICCs of 0.84¹⁶ and 0.91.⁹ The ICC greater than 0.7 further confirms the outstanding reliability of the UAS7. Sensitivity analysis shows that post-treatment UAS7 improvements correlate closely with patient and physician assessments of CSU activity changes. However, there was a notable difference in the correlation coefficients between the two, possibly due to subjective differences in symptom perception and interpretation by patients and physicians.

Our study used an SEM-based method to determine that the MDC for UAS7 is 5.08, which is consistent with the benchmark of 5.0 identified in prior research.⁹ This suggests that any changes exceeding this threshold are significant and not merely a result of random error. To further clarify, while MDC represents the smallest change that can be reliably measured beyond random error, MCID reflects the smallest change that is clinically meaningful to patients.²² Based on this, the MCID value we evaluate should be higher than the MDC value to ensure its clinical significance and effectiveness.

To identify the UAS7 change threshold that is clinically meaningful for patients, our study employed multiple methods to calculate the MCID and performed a comprehensive analysis. Although the distribution criterion method estimates MCID from a statistical perspective, it does not account for the specific disease activity changes. However, as results based on the distribution method did not exceed the MDC threshold, we do not recommend using this method for determining the MCID value.

In comparison, anchor-based methods are generally considered a more suitable choice. In this approach, we evaluated MCID from both patient (PatGA) and physician (PhyGA) perspectives. For PatGA, ‘moderate improvement’ was selected as the anchor criterion, aligning with the criterion that a clinical symptom improvement exceeding 50% is considered an effective treatment response.²³ For PhyGA, the estimated MCID values for 2-degree and 3-degree improvement were notably higher than those from previous studies on omalizumab intervention,^{9 20 21} while MCID value for 1-degree improvement better aligned with actual clinical scenarios. Hence, it was chosen as the anchor criterion.

In clinical practice, the assessment of treatment outcomes by both patients and physicians holds equal importance,²⁴ so the evaluation results of both should be considered comprehensively to formulate MCID. Accordingly, we recommend the MCID value of the UAS7 score for acupuncture treatment is 8.3 points, which is consistent with a score of 7–8 based on usual practice data.¹⁶ Additionally, it aligns closely with the MCID value of 7.5 proposed by Fan et al ¹³ in response to our previous study.⁷ The systematic reviews⁶ have shown that acupuncture is as effective as conventional antihistamine-based treatments, further validating our MCID value’s alignment with clinical reality.

Notably, our MCID value is lower than the 9.5–10.5^{20 21} and 11⁹ reported in previous pharmacological studies. This discrepancy might be attributed to differences in treatment protocols and patient disease characteristics.¹² These studies mainly involved patients with antihistamine-refractory chronic urticaria; whereas, our study did not differentiate between refractory and non-refractory CSU patients. Moreover, these studies used omalizumab, a second-line therapy recommended by guidelines¹ for patients unresponsive to first-line SgAH, typically showing greater effectiveness. Therefore, it is objectively reasonable for acupuncture, as an alternative therapy, to have a lower MCID value compared with omalizumab.

A key strength of this study lies in its novel application of MCID to acupuncture, a non-pharmacological intervention for CSU. This contributes to the growing body of evidence on the effectiveness of acupuncture in managing chronic conditions. However, this study has some limitations. (1) The study’s focus on CSU in an Asian population may limit the generalisability of findings to broader patient populations or other urticaria subtypes. (2) The methods used to determine the MCID have inherent considerations. Distribution-based methods, while statistically robust, may not always directly reflect individual patient experiences of meaningful change. Anchor-based methods can be influenced by the choice of anchor, potentially affecting result interpretation. (3) The study relied solely on post-treatment assessments, which could lead to recall bias, potentially affecting both the MCID estimation and overall treatment effect evaluation. (4) Although the study was adequately powered for the primary outcome, the limited sample size might restrict the precision of estimates, particularly in detecting smaller effect sizes. Despite these limitations, the study’s exploration of MCID in acupuncture treatment represents a significant step in understanding the effectiveness of non-pharmacological interventions for CSU.

Conclusion

This study provides initial insights into the clinical significance assessment of acupuncture for treating CSU, and we estimated the MCID value for the UAS7 to be 8.3. This threshold not only assists in identifying significant clinical changes in CSU treatment but also facilitates the comparison of alternative therapy effects in both clinical research and practice. Future studies should aim to validate these findings and explore the MCID values of acupuncture in treating other medical conditions.

Data availability statement

Data are available upon reasonable request. Data are available on reasonable request. Data supporting findings of this study are not publicly available as participants have not consented for their data to be publicly available.

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

This study involves human participants. The study protocol has been approved by the Sichuan Regional Committee for Traditional Chinese Medicine Research Ethics (ref no. 2018KL-047). Participants gave informed consent to participate in the study before taking part.

Footnote

Contributors XX, WC and ZZ designed the study. SC, QY, DQ and MX collected data for the study. XX, HQ and PX analysed the data. XX, HQ and LW contributed to the interpretation of data. XX, WC and ZZ drafted the manuscript. XX, YS and YL contributed to reading, commenting and approving the final manuscript. XX is responsible for the overall content as guarantor. We used Claude 3.5 Sonnet to help us check if the expressions in our manuscript are clear and fluent.

Funding This work was supported by the National Natural Science Foundation of China [grant numbers 82205283, 82105026, 82305410]; the Natural Science Foundation of Sichuan Provincial Department of Science and Technology [grant number 2024NSFSC0728]; and the China Postdoctoral Science Foundation [grant numbers 2022MD723719, 2021MD693787].

Competing interests None declared.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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