Introduction

Intragastric balloon (IGB) is a minimally invasive intervention used for obese patients who do not achieve adequate weight loss with standard medical therapy (SMT), which includes lifestyle interventions with or without pharmacological treatment. It is also an option for individuals who do not meet the criteria for bariatric surgery or choose not to undergo it. Despite its growing use, there is little data on the short and long-term effectiveness of IGB compared to SMT in randomized controlled trials (RCTs).

Aims & Methods

This systematic review and meta-analysis aimed to compare the efficacy of IGB therapy for at least six months versus SMT in the treatment of obesity, assessing outcomes at 6, 9, and 12 months. A comprehensive literature search was conducted in the MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome was the percentage of excess weight loss (%EWL), while secondary outcomes included absolute weight loss (AWL), percentage of total weight loss (%TWL), and body mass index reduction (BMIR). We calculated mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes. Meta-regression was performed using baseline body mass index (BMI) as a covariate, and subgroup analyses were conducted based on IGB type, baseline BMI, and pharmacological therapy in the SMT group.

Results

A total of 15 RCTs, including 1,961 patients, were included. Compared to SMT, IGB therapy resulted in significantly greater %EWL at 6 months (MD 16.80%; 95% CI [9.22%; 24.38%]), 9 months (MD 14.36%; 95% CI [7.67%; 21.04%]), and 12 months (MD 13.10%; 95% CI [10.43%; 15.77%]). IGB was also superior in AWL, %TWL, and BMIR across all time points (Table 1). Subgroup analyses revealed that results remained consistent regardless of pharmacological therapy use in the SMT group (p=0.77). The Orbera balloon showed superior %TWL at 6 months (p<0.01) and AWL at 6 months (test for subgroup differences with p=0.01), while the Spatz3 balloon demonstrated better %TWL at 9 months (p<0.01). Studies with a baseline BMI >40 kg/m² had significantly greater %TWL at 6 months (p=0.04) and AWL at 6 months (p<0.01) than those with BMI ≤40 kg/m². Meta-regression analysis indicated that higher baseline BMI was associated with greater AWL and BMIR at 6 months.

Conclusion

IGB therapy was significantly more effective than SMT, even when pharmacological therapy was included, leading to superior weight loss outcomes at 6, 9, and 12 months.

Table 1. Summary of findings.

References

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Introduction

While three JAK inhibitors are now available in Ulcerative Colitis (UC), no direct comparison exists between these drugs making difficult the hierarchization of these therapeutic options.

Aims & Methods

We performed a systematic review and network meta-analysis to compare the short and long-term efficacy of the three available JAK inhibitors (JAKi) (Tofacitinib/TOFA, filgotinib/FILGO, upadacitinib/UPA) in patients with moderat-to-severe UC.
We performed a systematic review and network meta-analysis (PRISMAguidelines) of randomized controlled trials (including post-hoc analyses) conducted in adults, evaluating the efficacy of JAKi in moderate-to-severe UC.
The outcome mesures were 1) steroid-free clinical remission (CFREM) after induction therapy (partial Mayo score ≤ 2), 2) CFREM with endoscopic improvement (endoscopic Mayo score ≤ 1) after induction therapy, 3) CFREM at one year among induction-responders, 4) CFREM at one year among patients in clinical remission after induction.
The network meta-analysis was carried out according to a random effects model. The results are presented as relative risk (RR) with 95% confidence interval. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ .
The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments.

Results

Nine studies were included in this network meta-analysis, including a total of 2015 patients.
TOFA 10mg bid, FILGO 200 mg qd and UPA 45mg qd were more effective than placebo to induce CFREM and CFREM with endoscopic improvement. Side-by-side comparisons between JAKi found a higher efficacy of UPA 45 mg qd versus FILGO 200 mg qd (RR=0.22[0.10; 0.45]) for induction but no other significant difference between JAKi. SUCRA ranking hierarchizes induction therapies as following : UPA 45 mg qd (0.99), TOFA 10mg bid (0.75), FILGO 200 mg qd (0.27) and placebo (0.01).
Among induction-responders, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with the following SUCRA ranking : UPA 30mg qd (0.85), TOFA 10mg bid (0.80), FILGO 200 mg qd (0.64), TOFA 5mg bid (0.56), UPA 15 mg (0.44), and placebo (0.01).
Among patients in CFREM after induction phase, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with a different ranking (SUCRA) : TOFA 10 mg bid (0.84), FILGO 200 mg bid (0.74), TOFA (5mg bid) (0 .66), UPA 30mg qd (0.63), UPA 15 mg (0.44) and placebo (0.09).

Conclusion

While this network meta-analysis confirms the efficacy of JAKi to induce and maintain CFREM in moderate-to-severe UC, UPA seems to be the most effective JAKi to induce and maintain CFREM. However, once CFREM achieved after induction, continuing the same dose than during induction such as TOFA (10mg bid) or FILGO 200 mg seems to be more effective than reducing the dose (UPA 30 mg or UPA 15 mg) to maintain remission highlighting the dose-efficacy relationship of JAKi.

Disclosure

Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda et Tillotts
Lecture fees from: Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma
Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda