Abstract: We included 12 RCTs (743 people). Among these RCTs, flexibility exercise training was compared to an untreated control group, land-based aerobic training, resistance training, or other interventions (i.e. Tai Chi, Pilates, aquatic biodanza, friction massage, medications). Studies were at risk of selection, performance, and detection bias (due to lack of adequate randomization and allocation concealment, lack of participant or personnel blinding, and lack of blinding for self-reported outcomes). With the exception of withdrawals and adverse events, major outcomes were self-reported and were expressed on a 0-to-100 scale (lower values are best, negative mean differences (MDs) indicate improvement). We prioritized the findings of flexibility exercise training compared to land-based aerobic training and present them fully here. Very low-certainty evidence showed that compared with land-based aerobic training, flexibility exercise training (five trials with 266 participants) provides no clinically important benefits with regard to HRQoL, pain intensity, fatigue, stiffness, and physical function. Low-certainty evidence showed no difference between these groups for withdrawals at completion of the intervention (8 to 20 weeks). Mean HRQoL assessed on the Fibromyalgia Impact Questionnaire (FIQ) Total scale (0 to 100, higher scores indicating worse HRQoL) was 46 mm and 42 mm in the flexibility and aerobic groups, respectively (2 studies, 193 participants); absolute change was 4% worse (6% better to 14% worse), and relative change was 7.5% worse (10.5% better to 25.5% worse) in the flexibility group. Mean pain was 57 mm and 52 mm in the flexibility and aerobic groups, respectively (5 studies, 266 participants); absolute change was 5% worse (1% better to 11% worse), and relative change was 6.7% worse (2% better to 15.4% worse). Mean fatigue was 67 mm and 71 mm in the aerobic and flexibility groups, respectively (2 studies, 75 participants); absolute change was 4% better (13% better to 5% worse), and relative change was 6% better (19.4% better to 7.4% worse). Mean physical function was 23 points and 17 points in the flexibility and aerobic groups, respectively (1 study, 60 participants); absolute change was 6% worse (4% better to 16% worse), and relative change was 14% worse (9.1% better to 37.1% worse). We found very low-certainty evidence of an effect for stiffness. Mean stiffness was 49 mm to 79 mm in the flexibility and aerobic groups, respectively (1 study, 15 participants); absolute change was 30% better (8% better to 51% better), and relative change was 39% better (10% better to 68% better). We found no evidence of an effect in all-cause withdrawal between the flexibility and aerobic groups (5 studies, 301 participants). Absolute change was 1% fewer withdrawals in the flexibility group (8% fewer to 21% more), and relative change in the flexibility group compared to the aerobic training intervention group was 3% fewer (39% fewer to 55% more). It is uncertain whether flexibility leads to long-term effects (36 weeks after a 12-week intervention), as the evidence was of low certainty and was derived from a single trial. Very low-certainty evidence indicates uncertainty in the risk of adverse events for flexibility exercise training. One adverse effect was described among the 132 participants allocated to flexibility training. One participant had tendinitis of the Achilles tendon (McCain 1988), but it is unclear if the tendinitis was a pre-existing condition. When compared with aerobic training, it is uncertain whether flexibility improves outcomes such as HRQoL, pain intensity, fatigue, stiffness, and physical function, as the certainty of the evidence is very low. Flexibility exercise training may lead to little or no difference for all-cause withdrawals. It is also uncertain whether flexibility exercise training has long-term effects due to the very low certainty of the evidence. We downgraded the evidence owing to the small number of trials and participants across trials, as well as due to issues related to unclear and high risk of bias (selection, performance, and detection biases). While flexibility exercise training appears to be well tolerated (similar withdrawal rates across groups), evidence on adverse events was scarce, therefore its safety is uncertain.

Plain-language summary: We searched the literature up to December 2017 and found 12 studies (743 individuals) that met our inclusion criteria. Flexibility interventions were compared with control (treatment as usual), aerobic training interventions (e.g. treadmill walking), resistance-training interventions (e.g. using weight machines that provide resistance to movement), and other interventions (e.g. Pilates). The average age of participants was 48.6 years. Trials were conducted in seven countries, and most studies (58.3%) included only female participants. Exercise trials ranged from 4 to 20 weeks. The stretching exercise programs ranged from 40 to 60 minutes, 1 to 3 times a day. The intensity of the stretches (e.g. how far the stretch was taken in the available range of motion) was not reported in most cases. The time each stretch was held ranged from 6 to 60 seconds. The targeted muscles were usually of both the upper and lower extremities, neck, and back. The flexibility training was either supervised or done at home. Our main comparison was flexibility exercise versus land-based aerobic training. Key results at the end of treatment for our main comparison Compared with land-based aerobic exercise training, flexibility exercise resulted in little benefit at 8 to 20 weeks' follow-up. Each measure below was measured on a scale from 0 to 100, with lower scores better. Health-related quality of life: People who received flexibility exercise training were 4% worse (ranging from 6% better to 14% worse). • People who had flexibility training rated their quality of life as 46 points. • People who had aerobic training rated their quality of life as 42 points. Pain intensity: People who received flexibility exercise training were 5% worse (ranging from 1% better to 11% worse). • People who had flexibility training rated their pain as 57 points. • People who had aerobic training rated their pain as 52 points. Fatigue: People who received flexibility exercise training were 4% better (ranging from 13% better to 5% worse). • People who had flexibility training rated their fatigue as 67 points. • People who had aerobic training rated their fatigue as 71 points. Stiffness: People who received flexibility exercise training were 30% better (ranging from 8% better to 51% better). • People who had flexibility training rated their stiffness as 49 points. • People who had aerobic training rated their stiffness as 79 points. Physical function: People who received flexibility exercise training were 6% worse (ranging from 4% better to 16% worse). • People who had flexibility training rated their physical function as 23 points. • People who had aerobic training rated their physical function as 17 points. Withdrawal from treatment A total of 18 per 100 people dropped out of the flexibility exercise training group for any reason compared to 19 per 100 people from the aerobic training group. Harms We found no clear information on harms. One study reported that one participant had swelling (tendinitis) of an ankle tendon (Achilles), but it is unclear if this was related to participation in the flexibility exercise. Quality of evidence The evidence does not show that flexibility exercise significantly improves health-related quality of life, pain, fatigue, or physical function. The number of people dropping out from each group was similar. Although the evidence suggests that flexibility exercise improves stiffness, caution is advised in interpretation of these results, as this improvement was seen in only one study with very few participants. We considered the overall certainty of the evidence to be low to very low due to study design issues, the small number of participants, and low certainty of results.