Fármacos antiinflamatorios no esteroideos (AINE) para el dedo en gatillo
Resumen
Antecedentes
El dedo en gatillo es una afección común de la mano que se produce cuando el movimiento del tendón flexor del dedo a través de la primera polea anular (A1) se ve afectado por degeneración, inflamación y tumefacción. Esto provoca dolor y restricción del movimiento del dedo afectado. Las opciones de tratamiento no quirúrgico incluyen la modificación de la actividad, los antiinflamatorios no esteroideos (AINE) orales y tópicos, el uso de férulas y las inyecciones locales con antiinflamatorios.
Objetivos
Revisar los efectos beneficiosos y perjudiciales de los antiinflamatorios no esteroideos (AINE) versus placebo, glucocorticoides o diferentes AINE administrados por la misma vía para el dedo en gatillo.
Métodos de búsqueda
Se realizaron búsquedas en CENTRAL, MEDLINE, Embase, CINAHL, CNKI (China National Knowledge Infrastructure), ProQuest Dissertations and Theses, www.ClinicalTrials.gov, y el portal de ensayos de la OMS hasta el 30 de septiembre de 2020. No se aplicaron restricciones con respecto al idioma ni el estado de publicación.
Criterios de selección
Se buscaron los ensayos controlados aleatorizados (ECA) y los ensayos cuasialeatorizados en participantes adultos con dedo en gatillo que compararon los AINE administrados por vía tópica, oral o inyectada versus placebo, glucocorticoides o diferentes AINE administrados por la misma vía.
Obtención y análisis de los datos
Dos o más autores de la revisión revisaron de forma independiente los informes, extrajeron los datos y evaluaron el riesgo de sesgo y la certeza de la evidencia según el método GRADE. Los siete desenlaces principales fueron la resolución de los síntomas del dedo en gatillo, los síntomas persistentes moderados a graves, la recurrencia de los síntomas, la amplitud total de movimiento activo del dedo, el dolor residual, la satisfacción del paciente y los eventos adversos. Los efectos del tratamiento se presentaron como razones de riesgos (RR) y diferencias de medias (DM) con intervalos de confianza (IC) del 95%.
Resultados principales
Se incluyeron dos ECA realizados en un ámbito hospitalario ambulatorio (231 participantes adultos, media de edad 58,6 años, 60% mujeres, 95% a 100% con enfermedad moderada a grave). Ambos estudios compararon una única inyección de un AINE no selectivo (12,5 mg de diclofenaco o 15,0 mg de ketorolaco) administrada a dosis inferiores a las normales con una única inyección de un glucocorticoide (20 mg o 5 mg de triamcinolona), con una duración máxima de seguimiento de 12 o 24 semanas.
En ambos estudios se detectó riesgo de sesgo de deserción y de realización. Un estudio también tenía riesgo de sesgo de selección. Los efectos del tratamiento fueron sensibles a las suposiciones sobre los desenlaces faltantes. En un estudio se informaron los siete desenlaces y cinco en el otro.
La inyección de AINE podría tener poco o ningún efecto beneficioso sobre la inyección de glucocorticoides, según evidencia de certeza baja a muy baja de dos ensayos. La calidad de la evidencia se disminuyó por el sesgo y la imprecisión. Podría haber poca o ninguna diferencia entre los grupos en la resolución de los síntomas a las 12 a 24 semanas (34% con AINE, 41% con glucocorticoides; efecto absoluto 7% menor, intervalo de confianza [IC] del 95%: 16% menor a 5% mayor; dos estudios, 231 participantes; RR 0,83; IC del 95%: 0,62 a 1,11; evidencia de certeza baja). La tasa de síntomas persistentes moderados a graves podría ser mayor a las 12 a 24 semanas en el grupo de AINE (28%) en comparación con el grupo de glucocorticoides (14%) (efecto absoluto 14% mayor; IC del 95%: 2% a 33% mayor; dos estudios, 231 participantes; RR 2,03; IC del 95%: 1,19 a 3,46; evidencia de certeza baja). No se sabe con certeza si los AINE dan lugar a menos recurrencias a las 12 a 24 semanas (1%) en comparación con los glucocorticoides (21%) (efecto absoluto 20% menor; IC del 95%: 21% a 13% menor; dos estudios, 231 participantes; RR 0,07; IC del 95%: 0,01 a 0,38; evidencia de certeza muy baja). Podría haber poca o ninguna diferencia entre los grupos en la media del movimiento activo total a las 24 semanas (235 grados con AINE, 240 grados con glucocorticoides) (efecto absoluto 5% menor; IC del 95%: 34,54% menor a 24,54% mayor; un estudio, 99 participantes; DM ‐5,00; IC del 95%: ‐34,54 a 24,54; evidencia de certeza baja). Podría haber poca o ninguna diferencia entre los grupos en el dolor residual a las 12 a 24 semanas (20% con AINE, 24% con glucocorticoides) (efecto absoluto 4% menor; IC del 95%: 11% menor a 7% mayor; dos estudios, 231 participantes; RR 0,84; IC del 95%: 0,54 a 1,31; evidencia de certeza baja). Podría haber poca o ninguna diferencia entre los grupos en el éxito del tratamiento informado por el participante a las 24 semanas (64% con AINE, 68% con glucocorticoides) (efecto absoluto 4% menor; IC del 95%: 18% menor a 15% mayor; un estudio, 121 participantes; RR 0,95; IC del 95%: 0,74 a 1,23; evidencia de certeza baja).
No hay certeza acerca de que la inyección de AINE tenga un efecto sobre los eventos adversos a las 12 a 24 semanas (1% con AINE, 1% con glucocorticoides) (efecto absoluto 0% de diferencia; IC del 95%: 2% menor a 3% mayor; dos estudios, 231 participantes; RR 2,00; IC del 95% 0,19 a 21,42; evidencia de certeza muy baja).
Conclusiones de los autores
En adultos con dedo en gatillo a las 24 semanas de seguimiento, los resultados de dos ensayos muestran que, en comparación con la inyección de glucocorticoides, la inyección de AINE dio lugar a poco o ningún efecto beneficioso en el tratamiento del dedo en gatillo. En concreto, no hubo diferencias en la resolución, los síntomas, la recurrencia, el movimiento activo total, el dolor residual, el éxito del tratamiento informado por el participante o los eventos adversos.
PICO
Resumen en términos sencillos
¿Qué tipos de medicamentos funcionan mejor cuando se inyectan en la mano para tratar un dedo hinchado y doloroso (dedo en gatillo)?
Mensajes clave
1. Una única inyección de un medicamento llamado AINE (antiinflamatorio no esteroideo) para tratar el dedo en gatillo produjo poco o ningún efecto beneficioso a los seis meses
2. Una inyección de un AINE podría no funcionar mejor que una inyección de un corticoide para tratar los síntomas del dedo en gatillo
3. Es posible que un mayor número de personas sigan presentando síntomas moderados o intensos entre tres y seis meses después de una inyección de AINE, en comparación con las que recibieron una inyección de corticoides
4. No hubo diferencias en el número de efectos no deseados notificados después de las inyecciones de uno u otro tipo de medicamento (con o sin corticosteroides)
¿Qué es el dedo en gatillo?
El dedo en gatillo es una enfermedad que afecta a uno o varios tendones de la mano. Los tendones son tejidos que unen el músculo al hueso y permiten mover las articulaciones. Cuando un tendón de la mano está inflamado, doblar el dedo afectado resulta difícil y doloroso. Sin tratamiento, el dedo afectado podría quedar permanentemente doblado, lo que dificulta las tareas cotidianas.
Tratamiento del dedo en gatillo
En algunas personas el dedo en gatillo puede mejorar sin tratamiento. Si no lo hace, los tratamientos incluyen:
1. descanso: evitar ciertas actividades;
2. fisioterapia;
3. fijar el dedo a una pieza de plástico (férula) para reducir el movimiento;
4. medicamentos conocidos como AINE que se toman por vía oral o directamente a través de la piel para reducir el dolor; y
5. medicamentos esteroideos inyectados para reducir la inflamación.
Si ninguno de estos tratamientos funciona, podría necesitarse la cirugía para ayudar a que el tendón vuelva a moverse libremente.
¿Por qué se ha realizado esta revisión Cochrane?
La inyección de corticosteroides en la mano para tratar el dedo en gatillo podría provocar efectos no deseados. Se quería determinar si la inyección de medicamentos AINE en la mano podía ayudar a las personas con dedo en gatillo y causar menos efectos no deseados que los corticosteroides.
¿Qué se hizo?
Se buscaron los estudios que estudiaron los medicamentos AINE inyectados para tratar el dedo en gatillo. Se compararon los resultados de los estudios encontrados para obtener a una estimación general de la eficacia de una inyección de AINE en el tratamiento del dedo en gatillo.
¿Cuál es el grado de actualización de esta revisión?
Se incluyó la evidencia hasta el 30 de septiembre de 2020.
¿Qué se encontró?
Se encontraron dos estudios en 231 adultos (edad promedio 59 años; 60% mujeres) que fueron tratados para el dedo en gatillo en clínicas ambulatorias en Singapur y Malasia. Un estudio duró tres meses y el otro seis meses. Un estudio no informó la fuente de financiación y el otro estudio no recibió financiación comercial.
En ambos estudios, las personas que participaron recibieron una inyección de:
1. un medicamento esteroideo (llamado triamcinolona); o
2. un AINE (diclofenaco o ketorolaco).
¿Cuáles son los resultados principales de esta revisión?
En comparación con una inyección de corticosteroides, una inyección de AINE podría tener poco o ningún efecto en:
1. que los síntomas desaparezcan (evidencia de dos estudios en 231 personas);
2. el grado de movilidad del dedo afectado de tres a seis meses después (un estudio en 99 personas);
3. cuántas personas siguen teniendo dolor después de tres a seis meses de tratamiento (dos estudios en 231 personas); y
4. cuántas personas dicen que su tratamiento fue exitoso (un estudio en 121 personas).
Como promedio, por cada 100 personas tratadas:
1. los síntomas podrían desaparecer después de tres meses en 34 personas que recibieron un AINE, en comparación con 41 personas que recibieron un corticoide;
2. 28 personas que recibieron un AINE podrían seguir teniendo síntomas de moderados a graves después de tres a seis meses, en comparación con 14 personas que recibieron un corticoide;
3. 20 personas que recibieron un AINE podrían seguir sintiendo dolor después de tres a seis meses, en comparación con 24 personas que recibieron un corticoide;
4. 64 personas que recibieron un AINE podrían decir que su tratamiento fue exitoso en comparación con 68 personas que recibieron un corticoide.
No se sabe si una inyección de AINE:
1. afecta la posibilidad de que los síntomas del dedo en gatillo vuelvan a aparecer después del tratamiento; ni si
2. causa menos efectos no deseados que una inyección de corticoides (evidencia de dos estudios en 231 personas).
Limitaciones de la evidencia
La confianza en los resultados es limitada porque proviene sólo de dos estudios pequeños. Estos estudios utilizaron diferentes dosis de corticoides para la inyección, lo que podría haber afectado la comparación de los estudios. Es probable que nuevos estudios de investigación cambien estos resultados o aumenten la confianza en ellos.
Authors' conclusions
Summary of findings
| NSAID injection compared to glucocorticoid injection for trigger finger | ||||||
| Patient or population: adults (> 18 years of age) with trigger finger | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | №. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with glucocorticoid injection | Risk with NSAID injection | |||||
| Resolution at 12 to 24 weeks Quinell Grade (range 0 to 4, resolved disease is grade 0) | 41 per 100 | 34 per 100 (25.4 to 45.5) | RR 0.83 | 231 | ⊕⊕⊝⊝ | NSAID injection may have little to no effect on resolution of symptoms Absolute difference 7% lower (16% lower to 5% higher),c risk ratio 17% lower (38% lower to 11% higher) |
| Persistent moderate to severe symptoms at 12 to 24 weeks | 14 per 100 | 28 per 100 (16.3 to 47.3) | RR 2.03 | 231 | ⊕⊕⊝⊝ | NSAID injection may result in more people with persistent moderate to severe symptoms Absolute difference 14% higher (2% higher to 33% higher), risk ratio 103% higher (19% higher to 246% higher) NNTH 7, 95% CI 3 to 38 |
| Recurrence at 12 to 24 weeks | 21 per 100 | 1 per 100 (0.2 to 7.8) | RR 0.07 | 231 | ⊕⊝⊝⊝ | It is uncertain if NSAID injection results in fewer people with recurrence of symptoms Absolute difference 20% lower (21% to 13% lower), risk ratio 93% lower (99% lower to 62% lower) NNTB 6, 95% CI 5 to 8 |
| Total active motion | Mean total active motion was 240 degrees | Mean total active motion was 5 degrees lower (34.54 degrees lower to 24.54 degrees higher) | ‐ | 99 | ⊕⊕⊝⊝ | NSAID injection may have little to no effect on total active motion Absolute difference 5% lower (34.54% lower to 24.54% higher), risk ratio 2.1% lower (14.8% lower to 10.2% higher) |
| Residual pain | 24 per 100 | 20 per 100 (12.9 to 31.4) | RR 0.84 | 231 | ⊕⊕⊝⊝ | NSAID injection may have little to no effect on residual pain Absolute difference 4% lower (11% lower to 7% higher), risk ratio 16% lower (46% lower to 31% higher) |
| Participant‐reported treatment success | 68 per 100 | 64 per 100 (50.1 to 83.3) | RR 0.95 | 121 | ⊕⊕⊝⊝ | NSAID injection may have little to no effect on treatment success Absolute difference 4% lower (18% lower to 15% higher), risk ratio 5% lower (26% lower to 23% higher) |
| Adverse events | 1 per 100 | 1 per 100h | RR 2.00 | 231 | ⊕⊕⊝⊝ | It is uncertain if NSAID injection results in fewer adverse events Absolute difference 0% (2% lower to 3% higher), risk ratio 0% (200% lower to 300% higher) |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group (steroid injection) and the relative effect of the intervention (and its 95% CI). The exception is the adverse events outcome, for which the absolute effect of the intervention is used (see Footnote 9). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aDowngraded by one level for risk of bias (high risk of selection and attrition bias). bDowngraded by one level for imprecision (95% CI supports both superiority for steroid injections and weak superiority for NSAID injections). cWith the exception of the adverse events outcome (see Footnote 10),the absolute effect is the simple difference between NSAID and steroid group risks in columns three and two of the table. dDowngraded by one level for imprecision (95% CI supports both superiority for steroid injection and no important difference between the two interventions). eDowngraded by two levels for risk of bias (high risk of selection and attrition bias; magnitude and precision of the pooled effect are highly sensitive to inclusion/exclusion of participants not at risk of recurrence; see Analysis 4.1). fDowngraded by one level for imprecision (95% CI supports substantial or weak superiority for NSAID injections). gDowngraded by one level for imprecision (95% CI supports superiority for steroid and NSAID injections). hThe risk in the intervention group was based on the pooled risk ratio because this effect uses data from both studies (Analysis 1.7), unlike the relative effect (see footnote below). iThis risk ratio estimate is based on only one study (Shakeel 2012), as the risk ratio of the excluded study ‐ Leow 2018 ‐ was not estimable due to zero adverse events in both treatment groups. jDowngraded by two levels for imprecision (data from only one study ‐ Shakeel 2012 ‐ and very few events). | ||||||
Background
Description of the condition
Trigger finger is a common condition that occurs when the gliding movement of an inflamed and swollen flexor tendon is obstructed by the narrowed osteofibrous canal of the first annular (A1) pulley, resulting in pain, clicking, catching, and loss of motion of the affected finger (Choudhury 2014). The A1 pulley is a fibrous condensation located at the metacarpophalangeal (MCP) joint. The forearm muscles that flex the fingers to enable grasping transmit force through long cord‐like flexor tendons that cross over the wrist and palm and attach to the fingers. To increase mechanical efficiency, these tendons slide through tunnel‐like tendon sheaths, which anchor the tendons closely to the volar surface of the finger bones (Peters‐Veluthamaningal 2009), in the same way that eyelets on a fishing rod constrain a tense fishing line to follow the curvature of the flexing rod. Trigger finger occurs when the smooth gliding movement of the flexor tendon through the A1 pulley is impaired by swelling of the tendon and the A1 pulley. This results in pain, clicking, catching, and restricted movement of the finger (Choudhury 2014; Makkouk 2008).
Trigger finger is a common hand condition with a prevalence of 2.6% in the general population (Makkouk 2008), more commonly affecting women and people in their fifth and sixth decades (Choudhury 2014). People who have arthritis and diabetes are more susceptible, with prevalence ranging from 5% to 36% (Cagliero 2002; Ray 2011). Trigger finger presents with different levels of severity. The most characteristic complaint is a finger stuck ("triggered") in the flexed position with difficulty returning to full extension (Choudhury 2014; Kolind‐Sørensen 1980; Peters‐Veluthamaningal 2009). It may eventually be released spontaneously with a snapping action (active correction) or with the help of the other hand (passive correction). In more severe cases, the finger may be locked in the bent position due to severe pain and mechanical tightness at the A1 pulley. In milder cases, patients may just experience uneven finger movements with accompanying discomfort and stiffness. Quinnell 1980 proposed a five‐point ordinal scale on which to grade the severity of trigger finger: Grade 0 – normal but possibly some mild crepitus during movement, Grade 1 – no triggering but uneven movement, Grade 2 – triggering but actively correctable, Grade 3 – triggering but passively correctable, Grade 4 – locked finger. Others have used very similar scales, with Grades 0 and 1 indicating no and mild disease, respectively, and Grade 4 indicating a fixed flexion (Eastwood 1992; Green 2005; Patel 1997).
Description of the intervention
The first line of treatment for trigger finger is conservative management, which involves activity modification, administration of topical or oral non‐steroidal anti‐inflammatory drugs (NSAIDs), and splinting (Choudhury 2014; Evans 1988; Patel 1992; Ryzewicz 2006). People with mild symptoms and those who have declined local injections and surgery are offered conservative treatment. Topical NSAIDs such as ketoprofen and oral NSAIDs such as ibuprofen are commonly given to relieve the pain caused by trigger finger. If conservative treatment fails, or if symptoms are severe (Quinell Grade 3 or 4), patients have the option of local glucocorticoid injections or surgery. A Cochrane Review has summarised the efficacy of glucocorticoid injections for trigger finger (Peters‐Veluthamaningal 2009). These injections are given locally at the affected A1 pulley. Variations in injection methods include palmar versus mid‐lateral approach (Jianmongkol 2007), at the A1 pulley versus at the proximal phalanx (Bodor 2009; Pataradool 2011), intra‐sheath versus extra‐sheath (Mardani‐Kivi 2018), and passing through versus not passing through the tendon substance (Akhtar 2006). It is thought that injectable NSAIDs might be an effective alternative to injectable glucocorticoids in situations where glucocorticoids are arguably contraindicated, as in diabetic patients with poor blood sugar control or in patients with infection or poor immunity (Leow 2017).
How the intervention might work
NSAIDs act via the arachidonic pathway, which involves inhibition of the cyclo‐oxygenase (COX) receptors, which in turn inhibits the synthesis of important pro‐inflammatory prostaglandins and blood clotting thromboxanes, resulting in reduced inflammation. NSAIDs are subdivided into two classes: (1) non‐selective NSAIDs, which inhibit both COX‐1 and COX‐2 enzymes, and (2) COX‐2‐selective NSAIDs (Waller 2013). The inflammation, swelling, and pain that impair tendon mobility are counteracted by the anti‐inflammatory and analgesic properties of NSAIDs.
The potent anti‐inflammatory effects of glucocorticoids are mediated by lipocortin‐1 (annexin‐1) synthesis and its downstream effects on phospholipase A2 synthesis and the arachidonic pathway. Glucocorticoids have a larger immunosuppressive effect than NSAIDs, as they work at the hormonal level and suppress the inflammatory process through numerous pathways (Barnes 2009).
Adverse effects of NSAIDs are primarily related to their inhibition of protective prostaglandins and thromboxanes, which increases the risk of adverse effects. Systemic events are expected to be more common with oral NSAIDs because of systemic absorption. These include hepatic injury, gastrointestinal irritation, ulcers, and bleeding, especially with non‐selective NSAIDs (Baigent 2013; Gabriel 1991; Ong 2007; Schneeweiss 2005; Sostres 2010); transient increase in blood pressure, heart attack, and stroke, especially with the thrombogenic COX‐2‐selective NSAIDs (Baigent 2013; Bresalier 2005; Kearney 2006); renal injury and hypertension due to inhibition of blood flow through the kidney (Thomas 2000); dry skin, rash, dermatitis, paraesthesia, pruritis, urticaria, and vesiculobullous rash (Makris 2007); and dizziness, vertigo, and headache (Makris 2007; Rannou 2016). Local events are relevant to topical or injectable NSAIDs but are not expected with an appropriate dosing schedule. Effects occur at the site of application or injection and include bleeding, pain, and allergic reactions.
Adverse effects of glucocorticoids occur at the site of injection and include bleeding, tendon rupture (Fitzgerald 2005; Gyuricza 2009; Wei 2006), skin thinning (Fitzgerald 2005; Gyuricza 2009), and discolouration due to effects on collagen metabolism (Brinks 2010; Friedman 1988). These effects are rare and are reported in very few case studies. Glucocorticoid injections are typically safe. Usually, there is a limit of three injections given at the same site. Systemic events are expected to be very uncommon for topical and local injections of glucocorticoids due to the local route of administration, which minimises systemic absorption. These events would be more common for oral glucocorticoids and may include infection and delayed healing due to immunosuppression (Coutinho 2011), transient hyperglycaemia due to effects on glucose synthesis and transport (Baumgarten 2007; Wang 2006), and allergic reactions.
Why it is important to do this review
Trigger finger is one of the most common hand conditions. Topical and oral NSAIDs are routinely prescribed as first‐line conservative treatment. Clinical experience shows that topical NSAIDs can help to relieve the pain and triggering caused by trigger finger. In people for whom the first line of treatment has failed, or in those with more severe cases, injectable glucocorticoids are an option. Our review summarises available evidence on the effectiveness, safety, and benefits of topical, oral, and injectable NSAIDs, and evaluates their effectiveness as an alternative to glucocorticoids.
Objectives
To review the benefits and harms of non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, glucocorticoids, or different NSAIDs administered by the same route for trigger finger.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials (RCTs) or quasi‐randomised trials were included. Quasi‐random methods of assignment to interventions are systematic methods that are not truly random, such as allocation by date of birth, hospital record number, or alternation. Studies reported as full text or only as an abstract and unpublished data were included. We applied no language restrictions.
Types of participants
Only studies of adults (older than 18 years) with a clinical diagnosis of trigger finger (triggering with or without locking of a finger or pain at the A1 pulley), irrespective of the duration of symptoms, were included. Studies of trigger finger caused by infection were excluded.
Types of interventions
We included all studies using traditional or COX‐2 selective NSAIDs administered topically, orally, or by injection. Comparators included placebo, glucocorticoids, or different NSAIDs delivered by the same route as the intervention.
Types of outcome measures
Follow‐up time points for the outcomes of interest were 4 weeks, 12 weeks, 24 weeks, 38 weeks, and 52 weeks.
Major outcomes
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Resolution of trigger finger symptoms (dichotomous: resolved/not resolved): resolution of symptoms was defined as a Quinell Grade (or equivalent) of 0; all other grades were classified as unresolved disease
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Persistent moderate to severe trigger finger symptoms (dichotomous: present/absent): moderate to severe symptoms was defined as a Quinell Grade of 2 or higher; Grade 1 was classified as mild, and Grade 0 as resolved
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Recurrence of trigger finger symptoms (dichotomous: recurring symptoms/no recurring symptoms): usually measured as the proportion with recurrence (definition of recurrence may vary across trials)
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Total active motion (continuous): defined as the investigator‐reported sum of active range of motion of the three finger joints (metacarpophalangeal, proximal interphalangeal, and distal interphalangeal) as measured by a goniometer in degrees; normal range of motion is as follows: metacarpophalangeal 19 to 71 degrees; proximal interphalangeal 23 to 87 degrees; distal interphalangeal 10 to 64 degrees (Bain 2014)
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Residual pain (dichotomous: pain/no pain): defined as participant‐reported residual pain or tenderness at the base of the finger
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Severity of pain: reporting of pain as a continuous outcome would be considered if visual analogue or other such pseudo‐continuous scales were used
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Participant‐reported treatment success (dichotomous: satisfied/not satisfied): defined as participant‐reported satisfaction with treatment
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Adverse effects of treatment (dichotomous: present/absent): defined as the investigator‐reported total number of adverse effects or complications of treatment
Search methods for identification of studies
Electronic searches
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE (1966 to 2020); Embase (1988 to 2020); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1937 to 2020); the China National Knowledge Infrastructure (CNKI; 1915 to 2020); and ProQuest Dissertations and Theses (1980 to 2020). A search of www.ClinicalTrials.gov and the World Health Organization (WHO) trials portal was also conducted (www.who.int/ictrp/en/). We applied no restriction on language of publication. The detailed search strategy for MEDLINE (Ovid) is provided in Appendix 1. This search strategy was adapted appropriately for the other electronic databases. The search was conducted on 30 September 2020.
Searching other resources
We checked the reference lists of all primary studies and review articles for additional references.
Data collection and analysis
Selection of studies
Two review authors (ML, QZ) independently screened titles and abstracts for possible inclusion. Two review authors (ML, SCT) independently screened the full‐text reports retrieved to confirm eligibility and to document reasons for exclusion. Any disagreement was resolved by consensus. Results at various stages of the selection process were recorded by using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram (prisma-statement.org/PRISMAStatement/Default.aspx; PRISMA Group).
Data extraction and management
Three review authors (ECSY, ML, QZ) independently extracted the following study data using a standard data collection form. Any disagreement was resolved by consensus.
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Methods: study design, total duration of study, details of any 'run‐in' period, number of study centres and locations, study settings, withdrawals, and dates of study.
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Participants: N, mean age, age range, sex, disease duration, severity of condition, diagnostic criteria, medical history of participants, inclusion criteria, and exclusion criteria.
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Interventions: name, dosage, route of administration, and concomitant and excluded medications.
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Outcomes: outcomes, treatment group statistics (i.e. number of events, means, standard deviations, and number of participants per treatment group), and time points. If outcomes for time points falling outside the pre‐specified values were reported, we extracted the data corresponding to a time closest to one of the pre‐specified time points to create as far as possible intention‐to‐treat (ITT) samples for analysis
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Characteristics of the design of the trial for assessment of risk of bias, including sources of funding and conflicts of interest
Assessment of risk of bias in included studies
Three review authors (ECSY, ML, QZ) independently assessed risk of bias for each study, using the Cochrane ’Risk of bias’ (RoB) tool (Higgins 2017). Two authors of this review are the authors of one of the studies included in this review (Leow 2018). This potential bias was resolved by having Renea Johnston from the Cochrane Musculoskeletal Group and an independent methodologist (ECSY) assess risk of bias, and by involving two methodologists (ECSY, QZ) in all critical steps (Contributions of authors). An independent methodologist (ECSY) assessed risk of bias, and two methodologists (ECSY, QZ) were involved in all critical steps to avoid bias (Contributions of authors).
Any disagreement was resolved by consensus. The following domains were graded as having high, low, or unclear risk of bias (RoB).
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Random sequence generation.
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Allocation concealment.
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Blinding of participants and study personnel (performance bias).
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Blinding of outcome assessment (detection bias).
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Incomplete outcome data.
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Selective outcome reporting.
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Other potential bias.
Separate RoB judgements were made for performance bias and detection of outcome bias. For performance bias, we considered blinding of participants and study personnel involved in treatment and caregiving. For detection bias, we separately assessed blinding of investigator‐reported outcome measurements (resolution, moderate to severe symptoms, recurrence, total active motion, and adverse events) and blinding of participant‐reported outcome measurements (pain and satisfaction).
Measures of treatment effect
We analysed dichotomous outcomes as risk ratios (RRs) or as Peto odds ratios when intervention effects were small or even zero, and we reported 95% confidence intervals (CIs). We analysed continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs), depending on whether the same scale was used to measure an outcome, and we reported 95% CIs. We entered data presented on a scale with a consistent direction of effect across studies.
When different scales were used to measure the same conceptual outcome (e.g. function), we planned to calculate SMDs, along with corresponding 95% CIs. We would back‐translate SMDs to a typical scale (e.g. 0 to 10 for pain) by multiplying the SMD by a typical among‐person standard deviation (e.g. standard deviation of the control group at baseline from the most representative trial), as per Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Schünemann 2017).
In the Effects of interventions section and in the 'Comments' column of the Characteristics of included studies table, we provided the absolute per cent difference, the relative per cent change from baseline, and the number needed to treat for an additional beneficial outcome (NNTB) (provided only when the effect was clinically significant). For dichotomous outcomes, we calculated the NNTB or the number needed to treat for an additional harmful outcome (NNTH) from the control group event rate and the risk ratio, using the Visual Rx NNT calculator (Cates 2016). We calculated the NNTB or the NNTH for continuous outcomes using the Wells calculator (available at the CMSG Editorial Office; http://musculoskeletal.cochrane.org/).
For dichotomous outcomes, we calculated the absolute risk difference using the risk difference statistic in Review Manager 5 (RevMan 2014), and we expressed the result as a percentage. For continuous outcomes, we calculated the absolute difference as the mean in the intervention group minus the mean in the control group, in original units, expressed as a percentage.
We derived the relative per cent change for dichotomous data as the risk ratio of 1 and expressed it as a percentage. For continuous outcomes, we calculated the relative difference in the change from baseline as the absolute difference divided by the mean of the control group, expressed as a percentage.
Unit of analysis issues
Each finger of a study participant was the unit of analysis; if multiple fingers from individual participants were included (i.e. those participants represent a cluster of units), we employed a variance inflating correction for the correlated outcomes from that study, if not already reported (Higgins 2011). If multiple trial arms were reported in a single trial, we included only the relevant arms. If two comparisons (e.g. drug A versus placebo and drug B versus placebo) were combined in the same meta‐analysis, we halved the control group to avoid double‐counting.
Dealing with missing data
Whenever possible, we contacted the study authors to verify key study characteristics and to obtain missing data.
For dichotomous outcomes, we performed an ITT analysis by using the total number of randomised participants as the denominator for group risks, with participants analysed in their randomised groups. When attrition caused missing outcome data, we presented the ITT analysis scenario, which assumed all study dropouts did not experience the outcome event (middle case 1 scenario) as the default analysis (see Sensitivity analysis). For continuous outcomes, we reported a per‐protocol analysis by using the number of participants who completed follow‐up.
Assessment of heterogeneity
We assessed clinical and methodological heterogeneity in terms of participants, interventions, outcomes, and study characteristics to determine if similarity was sufficient for meta‐analysis to be appropriate (see Characteristics of included studies). We quantified statistical heterogeneity by using the I² statistic (Deeks 2017), and we judged inconsistency by using the following guidelines: I² value of 0% to 40% 'might not be important'; 30% to 60% may represent 'moderate' heterogeneity; 50% to 90% may represent 'substantial' heterogeneity; and 75% to 100% represents 'considerable' heterogeneity (Deeks 2017).
Assessment of reporting biases
We checked trial protocols against published reports to assess outcome reporting bias. For studies published after 1 July 2005, we screened the WHO International Clinical Trials Registry Platform for prospectively written trial protocols (www.who.int/ictrp/en/). We reported any commercial funding or serious conflict of interest in the "Other bias" domain. If we identified sufficient studies, and if all other major biases (except publication bias) could be ruled out (Sterne 2017), we examined a funnel plot for asymmetry; otherwise a funnel plot would not be produced.
Data synthesis
We estimated pooled effects only when there was meaningful clinical and methodological similarity; pooling was done by using a random‐effects (RE) model.
Subgroup analysis and investigation of heterogeneity
If data were available, we planned subgroup analyses to explore differences in treatment effects for participants with diabetes mellitus. We found that these patients had poorer treatment outcomes with glucocorticoids and could benefit from NSAIDs (Baumgarten 2007).
Outcomes that we will include in the subgroup analysis include resolution and the severity of trigger finger (e.g. Quinnell grading; Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire) and pain score obtained from a visual analogue scale (VAS).
Sensitivity analysis
When relevant, we assessed the robustness of the meta‐analyses for reviewer decisions in the following areas.
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Resolution and recurrence outcomes: inclusion/exclusion of studies at high or unclear risk of selection bias.
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Participant‐reported (subjective) outcomes: inclusion/exclusion of studies with inadequate or unclear participant blinding (this was not done, as participant blinding was adequate in all studies).
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Method of imputing missing events in the ITT analysis of dichotomous outcomes for participants who were lost to follow‐up (we compared analyses for four ITT data imputation scenarios described in Table 1 and Table 2 for benefit and harm dichotomous outcomes, respectively).
| ITT scenarios | Dropouts assumed to have the good outcome | |
| NSAID group | Steroid group | |
| Best case (for NSAID) | yes | no |
| Middle case 1 | no | no |
| Middle case 2 | yes | yes |
| Worst case (for NSAID) | no | yes |
ITT: intention‐to‐treat.
NSAID: non‐steroidal anti‐inflammatory drug.
| ITT scenarios | Dropouts assumed to have the bad outcome | |
| NSAID group | Steroid group | |
| Best case (for NSAID) | no | yes |
| Middle case 1 | no | no |
| Middle case 2 | yes | yes |
| Worst case (for NSAID) | yes | no |
ITT: intention‐to‐treat.
NSAID: non‐steroidal anti‐inflammatory drug.
Summary of findings and assessment of the certainty of the evidence
We created a 'Summary of findings' (SoF) table for the NSAID injection/glucocorticoid injection comparison using the following outcomes at the final time point.
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Resolution of trigger finger.
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Moderate to severe symptoms of trigger finger.
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Recurrence of trigger finger.
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Total active motion of the finger.
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Residual pain.
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Severity of pain.
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Participant‐reported treatment success.
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Adverse effects of treatment.
Two review authors (ML, QZ) independently assessed the quality of the evidence. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence as it relates to studies that contributed data to the meta‐analyses for pre‐specified outcomes, and we reported the quality of evidence as high, moderate, low, or very low. We used GRADEpro software to prepare the SoF tables (GRADEpro GDT 2015). We justified all decisions to downgrade the quality of studies by using footnotes, and we made comments to aid the reader's understanding of the review when necessary. We were aware of distinguishing lack of evidence of effect from lack of effect (Schünemann 2017). We based our conclusions only on findings from the quantitative or narrative synthesis of included studies for this review. We avoided making recommendations for practice, and our implications for research suggest priorities for future research and outline remaining uncertainties in this area.
Results
Description of studies
See the Characteristics of included studies and Characteristics of excluded studies tables.
Results of the search
The latest search results (up till September 2020) are shown in Figure 1. We conducted full‐text screening of 67 records (MEDLINE: 23, Embase: 33, CENTRAL: 5, CINAHL: 6). Overall, we included two studies (Leow 2018; Shakeel 2012), and we excluded 56 studies. We identified no ongoing studies and no studies awaiting classification. Of the excluded studies, we excluded 22 because they examined non‐trigger finger, 27 because they were not RCTs, and seven because they did not include an NSAID treatment arm. We found no records in CNKI nor in ProQuest Dissertations and Theses.
Study flow diagram.
Included studies
We included two RCTs (221 participants; one digit per participant) evaluating the efficacy and safety of an injectable NSAID versus an injectable glucocorticoid (Leow 2018; Shakeel 2012). They included 75 males and 146 females. The mean age of participants in Shakeel 2012 was 60 years, and the mean age of participants in Leow 2018 was 57.5 years.
We found no studies of oral or topical NSAIDs and no studies that compared NSAIDs by any route with placebo or another NSAID.
Participants
Both studies recruited adults without previous injections at the finger site. The study population in Shakeel 2012 had slightly more severe disease ‐ all were Quinell Grade 2 or higher (64% Grade 2, 29% Grade 3, and 7% Grade 4). Leow 2018 included a small proportion with Grade 1 (mild) disease (7.4%), 61.2% with Grade 2, 31.4% with Grade 3, and none with Grade 4 disease. Quinnell 1980 proposed a five‐point ordinal scale to grade the severity of trigger finger: Grade 0 – normal but possibly some mild crepitus during movement, Grade 1 – no triggering but uneven movement, Grade 2 – triggering that is actively correctable, Grade 3 – triggering that is passively correctable, Grade 4 – locked finger. Moderate to severe symptoms were defined as Quinell Grade 2 or higher; Grade 1 was classified as mild; and Grade 0 was resolved. Hand dominance was not recorded in either study.
Interventions
Both studies used single injections of a non‐selective NSAID at lower doses than are typically used in injections. Shakeel 2012 used diclofenac sodium at half the typically used dose (12.5 mg), and Leow 2018 used ketorolac trometamol at one‐quarter (15 mg) the typically used dose in combination with 5 mg 1% lidocaine. Both studies used single injections of triamcinolone acetonide as the control. Shakeel 2012 used 20 mg triamcinolone, and Leow 2018 used 5 mg in combination with 5 mg 1% lidocaine. Shakeel 2012 used an exclusively intrasynovial injection technique; Leow 2018 used combined intrasynovial and extrasynovial injections.
Outcomes
The outcomes measured in Shakeel 2012 were reported at three time points ‐ baseline (time of injection), 3 weeks, and 3 months. Those measured in Leow 2018 were reported at five time points ‐ baseline, 3 weeks, 6 weeks, 12 weeks, and 24 weeks.
Shakeel 2012 used Quinell grades (Table 1), and Leow 2018 used Green's version (Green 2005). Moderate to severe symptoms were defined as Quinell Grade 2 or higher; Grade 1 as mild; and Grade 0 as resolved disease. Both studies defined disease resolution as achieving a grade of zero as assessed by the investigator at the end of follow‐up.
Recurrence of trigger finger symptoms in participants who experienced temporary resolution was reported by Leow 2018; in Shakeel 2012, recurrence was reported but was not explicitly defined.
Pain was measured as a dichotomous outcome in Shakeel 2012 in Leow 2018, pain was measured on a 0 to 10 rating scale and was also reported as a dichotomous outcome (present/absent).
Total active motion and participant satisfaction were reported only by Leow 2018.
Both studies reported adverse events.
Excluded studies
We excluded 56 studies for the following reasons: 22 studies were not about trigger finger (Akdogan 2014; Al‐Homood 2013; Alvarez‐Nemegyei 2004; Andreu 2011; Coleman 2008; Farouk 2010; Gheita 2011; Gigante 2011; Giuliani 2015; Hardy 2013; Heffernan 2001; Lebiedz‐Odrobina 2010; Lintermans 2011; Londono 2012; Reading 2001; Sainsbury 2008; Sheon 1997; Silva 2012; Vega‐Morales 2014; Waimann 2011; Woo 2017; Wysocki 2012); 27 were not RCTs (Akhtar 2005; Bullocks 2009; Choudhury 2014; Crop 2011; Davidson 2011; Egido 2008; Harvard News Letter 2017; Lim 2007; Huisstede 2010; Jacobs 2009; Jacobs 2013; Kamath 2016; Kim 2011; Lim 2017; Ma 2019; Massoud 2018; Mutlu 2017; Nimigan 2006; Panayotopoulos 1992; Pargali 2011; Park 2009; Saldana 2001; Sayilir 2017; Schulman 2013; Soto Quijano 2005; Taras 2010; Wiwanitkit 2012); and seven did not include an NSAID intervention arm (Anderson 1991Chao 2009; Foster 2015; Ilyas 2019; Kosiyatrakul 2018Peters‐Veluthamaningal 2009; Weinheimer 2019).
Risk of bias in included studies
The risk of bias (RoB) assessment is summarised in Figure 2 and in the Characteristics of included studies tables.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Random sequence generation
We judged Leow 2018 as having low RoB, as the sequence generation was computerised and baseline characteristics were reported and judged as balanced.
Shakeel 2012 used a physical method (drawing marked slips from a container) to randomise treatment. However these researchers did not assess the success of the procedure in balancing baseline characteristics, nor did they report a table of baseline characteristics, so we judged the RoB as unclear.
Allocation concealment
Leow 2018 implemented the allocation through opaque, sequentially numbered envelopes. These envelopes were opened by a research assistant (who was not involved in the treatment or outcome assessment process) after the participant had consented, so we judged the RoB to be low.
In Shakeel 2012, the treatment slips in the container were openly marked with the treatment names "NSAID" or "STEROID", instead of a more secure numerical code (decipherable only by the trial pharmacist). So it would have been possible for a study team member to pre‐draw the slips and create an unblinded random treatment allocation schedule. Even if the slips were drawn in real time and were not pre‐drawn, awareness of the assigned treatment could have influenced the behaviour of the recruiter. As a result, we judged the RoB to be high.
Blinding
Performance bias
Blinding of participants
In both studies, participants were blinded.
Blinding of study personnel
In both studies, study personnel were not blinded.
For both studies, we judged the risk of performance bias as unclear.
Detection bias
Investigator‐reported outcomes
In both studies, these outcomes were measured by blinded assessors, and we judged RoB as low.
Participant‐reported outcomes
In both studies, participants were blinded, and we judged RoB as low.
Incomplete outcome data
In Leow 2018, the attrition rate at 12 weeks (3 months), which is the measurement time point most similar to the latest time point in Shakeel 2012, was 23.7% (NSAID) and 22.6% (glucocorticoid); and at 24 weeks, the attrition rate was 20.3% (NSAID) and 16.1% (glucocorticoid). No reasons were given (except for three participants in the NSAID group who opted for surgery). Study authors performed a per‐protocol analysis that excluded the study dropouts (per personal communication with study author).
In Shakeel 2012, the attrition rate at 3 months was 9.1% in both groups. A per‐protocol analysis (excluding the 10 who did not complete the 3‐month follow‐up) was done.
In both studies, all attrition rates are comparable in magnitude to the outcome event rates, thus making the treatment effects sensitive to assumptions about the outcome status of those who dropped out. We therefore judged RoB as high.
Selective reporting
In both studies, the major outcomes of resolution and moderate to severe symptoms could be determined for all time points mentioned in the Methods section. Even though the results were not reported as point estimates with confidence intervals, we obtained sufficient detail to estimate treatment effects and 95% CIs for all review outcomes measured at the latest follow‐up times. We judged RoB as low.
Other potential sources of bias
Funding for Leow 2018 was received from non‐commercial sources, and the study was judged at low RoB, Shakeel 2012 did not mention study funders, and we judged RoB for this study as unclear.
Effects of interventions
See: Summary of findings 1 NSAID injection compared to glucocorticoid injection for trigger finger
All review outcomes were reported in at least one study. Outcomes were measured at multiple time points ‐ 3 weeks and 3 months for Shakeel 2012, and 3, 6, 12, and 24 weeks for Leow 2018. Except for Quinnell grades for disease severity, group results for the other outcomes were not reported in full. All investigator‐reported analyses were based on those who completed follow‐up. In both studies, no treatment effect estimates or 95% CIs were reported ‐ only P values. However reported data were sufficient for us to calculate some effect estimates and CIs for the latest follow‐up time point of 24 weeks for Leow 2018 and 3 months (taken as 12 weeks) for Shakeel 2012. We expressed these in a standardised statement, which incorporates a judgement about the clinical importance, direction, and certainty of evidence of the effect (see Data synthesis). We performed sensitivity analyses for various reasons; these are described under the relevant outcome headings.
The only comparison reported was NSAID injection versus glucocorticoid injection (see summary of findings Table 1).
NSAID injection versus glucocorticoid injection
Major outcomes
Resolution of trigger finger symptoms
Shakeel 2012 measured the severity of trigger finger symptoms using Quinnell grading. However, Leow 2018 used a modified Quinell grading system, which distinguishes between required passive extension (Grade 3a) and inability to actively flex (Grade 3b) for Grade 3 trigger finger, and does not include Grade 4 for a "locked" finger. At baseline, 92.6% (112/121) of participants in Leow 2018 had severe disease (Quinnell Grade 2 or higher) compared to 100% in Shakeel 2012.
Our analysis pooled outcomes measured at 24 weeks in Leow 2018 with those measured at 12 weeks in Shakeel 2012 (Analysis 1.1). For a sensitivity analysis, we pooled only 12‐week outcomes from both studies. The RR of symptom resolution at 12 to 24 weeks was 0.83 in favour of glucocorticoid injection (95% CI 0.62 to 1.11 times higher), and the absolute effect was 7% lower in favour of glucocorticoid injection (95% CI 16% lower to 5% higher); the risk difference was 17% lower (95% CI 38% lower to 11% higher) (Analysis 1.1; summary of findings Table 1). For adults with trigger finger, NSAID injection may make little to no difference in the chance of symptom resolution at 12 to 24 weeks compared to glucocorticoid injection (2 studies, 231 participants; low‐certainty evidence, downgraded for bias and imprecision).
Persistent moderate to severe trigger finger symptoms
This outcome measures the failure of treatment to reduce symptom severity from what was initially a moderate or severe condition to a mild or resolved condition (i.e. persistently moderate or severe symptoms at the end of follow‐up) (Quinnell Grade 2 or higher).
For adults with trigger finger, NSAID injection may increase the chance of persistent moderate to severe symptoms at 12 to 24 weeks compared to glucocorticoid injection (2 studies, 231 participants). The RR of persistent moderate to severe symptoms at 12 to 24 weeks was 2.03 in favour of glucocorticoid injection (95% CI 1.19 to 3.46 times higher) (Analysis 1.2; summary of findings Table 1). The absolute risk is 14% higher in favour of glucocorticoid injection (95% CI 2% to 33% higher) and the risk difference is 103% higher in favour of glucocorticoid injection (95% CI 19% to 246% higher) (NNTH 7, 95% CI 3 to 38; low‐certainty evidence, downgraded for bias and imprecision).
Recurrent trigger finger symptoms
Leow 2018 reported recurrence in the glucocorticoid injection group as a percentage only; exact numbers of events and definitions were obtained by personal communication. Our default analysis counted all randomised participants in the denominator for risk calculations. We also conducted a sensitivity analysis using only participants at risk of recurrence in the denominator of the risk calculations (i.e. those participants who had experienced initial resolution of symptoms during follow‐up).
For adults with trigger finger, it is very uncertain whether NSAID injection decreases the chance of symptom recurrence at 12 to 24 weeks compared to glucocorticoid injection (2 studies, 231 participants). The RR of symptom recurrence at 12 to 24 weeks was 0.07 in favour of NSAID (95% CI 0.01 to 0.38 times higher) (Analysis 1.3summary of findings Table 1) (NNTB 6, 95% CI 5 to 8; very low‐certainty evidence, downgraded by two levels for bias and by one level for imprecision).
Total active motion
Only Leow 2018 reported total active range of motion. This is an objective measure of unaided mobility of the three finger joints. A per‐protocol analysis of this continuous outcome is reported.
For adults with trigger finger, NSAID injection may make little to no difference in mean total active motion at 24 weeks compared to glucocorticoid injection. Mean total active range of motion for each group was 235 degrees (NSAID) and 240 degrees (glucocorticoid). The mean difference in total active range of motion at 24 weeks was 5 degrees less in favour of glucocorticoid injection (95% CI 35.54 less to 24.54 more), absolute difference was 5% lower (95% CI 34.54% lower to 24.54% higher), and risk difference was 2.1% lower (95% CI 14.8% lower to 10.2% higher) (Analysis 1.4; summary of findings Table 1) (1 study, 99 participants; low‐certainty evidence, downgraded for bias and imprecision).
Residual pain
Leow 2018 measured residual pain on a 0 to 10 scale, with 0 signifying "no pain". This original analysis was based on comparison of median pain scores. To enable pooling with pain data from Shakeel 2012, a dichotomous outcome was defined (pain/no pain). Compared to Leow 2018, Shakeel 2012 reported considerably fewer residual pain events described as continuous pain at the injection site and classified as a "complication" (adverse event), but they opine that this pain could be unresolved pain from the trigger finger rather than a genuine adverse event. Our default analysis assumes this is residual pain from the presenting disease. But we also performed a sensitivity analysis in which this was not counted and in which suspected under‐reporting of pain was adjusted for by assuming all participants with moderate disease at the end of follow‐up had residual pain (Shakeel 2012).
For adults with trigger finger, NSAID injection may make little to no difference in the chance of residual pain at 12 to 24 weeks compared to glucocorticoid injection. The RR of residual pain at 12 to 24 weeks was 0.84 in favour of NSAID (95% CI 0.54 to 1.31 times higher), absolute difference was 4% lower (95% CI 11% lower to 7% higher), and risk difference was 16% lower (95% CI 46% lower to 31% higher) (2 studies, 231 participants; low‐certainty evidence, downgraded for bias and imprecision) (Analysis 1.5; summary of findings Table 1).
Participant‐reported treatment success
Only Leow 2018 reported participant satisfaction with treatment.
For adults with trigger finger, NSAID injection may make little to no difference in the chance of participant satisfaction at 24 weeks compared to glucocorticoid injection. The RR of participant‐reported treatment success at 24 weeks was 0.95 in favour of glucocorticoid injection (95% CI 0.74 to 1.23 times higher), absolute difference was 4% lower (95% CI 18% lower to 15% higher), and risk difference was 5% lower (95% CI 26% lower to 23% higher) (1 study, 121 participants; low‐certainty evidence, downgraded for bias and imprecision) (Analysis 1.6; summary of findings Table 1).
Adverse events
Leow 2018 reported no adverse events in either group. Shakeel 2012 reported "complications", but of the eight reported in the NSAID group, we did not consider six of them to be adverse effects of treatment (five nodular swellings and stiffness at the injection site, one recurrence of triggering). We regarded these as residual symptoms of unresolved disease. Therefore we counted only two adverse events in the NSAID group (both were continuous mild dull aches at the injection site). In the glucocorticoid injection group, ten "complications" were reported, one of which was continuous pain at the injection site and nine recurrences of triggering; we excluded recurrence events and counted only one adverse event in the glucocorticoid injection group. This would be consistent with a systematic review that reported pain at the injection site as a possible adverse reaction following glucocorticoid injection (Brinks 2010).
For adults with trigger finger, It is uncertain if NSAID injection results in fewer adverse events at 12 to 24 weeks compared to glucocorticoid injection. The pooled RR of adverse events at 12 to 24 weeks was not estimable due to zero events in both treatment groups in the Leow 2018 study (Analysis 1.7; summary of findings Table 1). The estimate from just Shakeel 2012 was RR 2.00 in favour of glucocorticoid injection (95% CI 0.19 to 21.42 times higher) (2 studies, 231 participants; very low‐certainty evidence, downgraded by one level for bias and by two levels for imprecision).
Sensitivity analysis
Resolution of trigger finger symptoms
Excluding Shakeel 2012 because of high risk of selection bias leaves just Leow 2018 from which to estimate the effect of treatment on symptom resolution, for an RR of 0.97 compared to the pooled estimate of 0.83, both favouring glucocorticoid injection (Analysis 1.1). Comparison of various ITT scenarios was based on different assumptions about outcome events among participants who were lost to follow‐up (Analysis 2.1). Leow 2018 reported 12 and 10 dropouts in NSAID and glucocorticoid groups, respectively; Shakeel 2012 reported 5 dropouts in each group. Scenario RRs ranged from 0.67 (favouring glucocorticoid) to 1.30 (favouring NSAID). The two middle scenarios had RRs of 0.83 and 0.90 (favouring glucocorticoid injection). Sensitivity to missing data assumptions supports a high risk of attrition bias judgement (Figure 2). Comparing pooling of the 12‐week outcome in Shakeel 2012 with 12‐ or 24‐week outcomes in Leow 2018 revealed favouring of glucocorticoid injection, with a pooled estimate of 0.32 (0.03, 3.03) at 12‐week and 0.83 (0.62, 1.11) at 24‐week follow‐up (Analysis 3.1).
Persistent moderate to severe trigger finger symptoms
Excluding Shakeel 2012 because of high risk of selection bias leaves just Leow 2018 from which to estimate the effects of treatment on persistent symptoms, for an RR of 1.84 compared to the pooled estimate of 2.03, both favouring glucocorticoid injection (Analysis 1.2). When various ITT scenarios were compared (Analysis 2.2), scenario RRs ranged from 1.06 to 3.11 (favouring glucocorticoid injection). The two middle scenarios had RRs of 1.62 and 2.03 (favouring glucocorticoid injection). When pooling of the 12‐week outcome in Shakeel 2012 was compared with pooling of 12‐ or 24‐week outcomes in Leow 2018 (Analysis 3.2), RRs ranged from 2.03 to 3.20 (favouring glucocorticoid injection).
Recurrent trigger finger symptoms
Excluding Shakeel 2012 because of high risk of selection bias leaves just Leow 2018 from which to estimate the effect of treatment on recurrence, for an RR of 0.03 compared to the pooled estimate of 0.07, both favouring NSAID (Analysis 1.3). When various ITT scenarios were compared (Analysis 2.3), scenario RRs ranged from 0.05 to 0.78 (favouring NSAID). The two middle scenarios had RRs of 0.07 and 0.48 (favouring NSAID). When pooling only of participants at risk of symptom recurrence in the denominator of the risk calculation was compared with pooling of all randomised participants (our default analysis) (Analysis 4.1), pooled RRs ranged from 0.07 to 0.13 (favouring NSAID). The larger effect in favour of NSAID seen in the "at risk" analysis is highly imprecise (95% CI ‐0.70 to 0.01), with high heterogeneity (I² = 88%).
Residual pain
When various ITT scenarios were compared (Analysis 2.4), scenario RRs ranged from 0.58 (favouring NSAID) to 2.26 (favouring glucocorticoid injection). The two middle scenarios had RRs of 0.84 and 0.95 (favouring NSAID). When three pain outcome scenarios ‐ including or excluding persistent pain as a bona fide pain outcome and assuming the presence of residual pain among Shakeel 2012 study participants who had Grade 2 severity at the end of follow‐up ‐ were compared (Analysis 5.1), RRs ranged from 0.82 (favouring NSAID) to 1.36 (favouring glucocorticoid).
Participant‐reported treatment success
When various ITT scenarios were compared (Analysis 2.5), scenario RRs ranged from 0.77 (favouring glucocorticoid injection) to 1.25 (favouring NSAID). The two middle scenarios had RRs of 0.95 (favouring glucocorticoid) and 1.01(favouring NSAID).
Adverse events
When various ITT scenarios were compared (Analysis 2.6), pooled scenario RRs ranged from 0.12 (favouring NSAID) to 11.13 (favouring glucocorticoid). The two middle scenarios had RRs of 0.77 (favouring NSAID) and 2.00 (favouring glucocorticoid). Shakeel 2012 opined that the three "continuous pain at injection site" events could be persistent symptoms of the disease rather than true adverse events. A subsequent sensitivity analysis included and excluded these events as adverse events (Analysis 6.1).
Discussion
For this review, we found two studies with 221 participants (aged 40 to 87 years) that compared the effectiveness of non‐steroidal anti‐inflammatory drug (NSAID) and glucocorticoid injections for adults with trigger finger (Leow 2018; Shakeel 2012). Both studies used non‐selective NSAIDs. No studies examined oral, topical, or cyclo‐oxygenase (COX)‐2‐selective NSAIDs or non‐injectable glucocorticoids or placebo.
Summary of main results
Our comparative analyses treated the NSAID injection as the experimental intervention and glucocorticoid as the comparator. Evidence is presented from the perspective of our working hypothesis that injectable NSAIDs might be clinically superior to injectable glucocorticoids.
Evidence on outcomes ranged from low to very low certainty. We found low‐certainty evidence for resolution, persistent moderate to severe symptoms, pain, total active motion, and treatment success reported by participants, and very low‐certainty evidence for recurrence and adverse events.
We considered resolution of symptoms by the end of follow‐up as the most stringent criterion of treatment success, by which absence of symptoms can be considered successful treatment. In this review, low‐certainty evidence suggests that a single NSAID injection may have little to no effect on resolution of symptoms compared with glucocorticoid injection at 12 to 24 weeks. Due to risk of selection and attrition bias and imprecision, we determined the certainty of evidence to be low.
Low‐certainty evidence suggests that a single NSAID injection may result in more people with persistent moderate to severe symptoms compared to a glucocorticoid injection. Data show that NSAID injection may even increase the chance of unresolved symptoms at 12 to 24 weeks. Due to risk of selection and attrition bias and imprecision, we determined the certainty of evidence to be low.
It is uncertain if NSAID injection results in fewer people with recurrence of symptoms due to very low‐certainty evidence; we do not know if there are differences in recurrence rates between groups. The evidence is of very low certainty, downgraded twice for bias and once for imprecision.
Low‐certainty evidence suggests that a single NSAID injection may have little to no effect on total active motion compared with a glucocorticoid injection. The difference of 5 degrees in favour of glucocorticoid is small and is distributed over the range of motion of three joints; we judged this difference to be clinically not significant. Due to risk of selection and attrition bias and imprecision, we determined that the certainty of evidence is low.
Low‐certainty evidence suggests that a single NSAID injection may have little to no effect on residual pain. Concern about the accuracy of reporting of pain in Shakeel 2012 was caused by uncertainty as to whether pain was a presenting symptom or an adverse effect caused by the intervention, or whether pain was under‐reported by participants. Our sensitivity analyses indicate that the default analysis is robust. Due to risk of selection and attrition bias and imprecision, we determined that the certainty of evidence is low.
Low‐certainty evidence suggests that a single NSAID injection may have little to no effect on treatment success. The risk difference of 5% in favour of glucocorticoid is small, and we judged it to be clinically not significant. Due to risk of selection and attrition bias and imprecision, we determined that the certainty of evidence is low.
All reported adverse events were local and were related to the injection procedure. Evidence is of very low certainty, downgraded once for bias and twice for imprecision, and It is uncertain if NSAID injection results in fewer adverse events.
Overall completeness and applicability of evidence
Overall, we found very limited to no randomised controlled trial (RCT) evidence that addresses the objectives of this review. We identified only two eligible studies for the current review (221 participants randomised; 199 study completers) that used lower than normal concentrations of two different non‐selective injectable NSAIDs in comparison with two different doses of triamcinolone glucocorticoid injection (5 and 20 mg). In one study, 5 mg of 1% lidocaine was used as a co‐intervention in both treatment groups. The longest follow‐up times were limited to between 12 and 24 weeks; two follow‐up time points were common to both studies ‐ 3 weeks and 12 weeks. We found small numbers of adverse events reported in the two included studies.
Doses of glucocorticoid (triamcinolone acetonide) given in the two studies were different (Leow 2018; Shakeel 2012). Shakeel 2012 used 20 mg triamcinolone acetonide, and Leow 2018 used 10 mg triamcinolone acetonide. This could have resulted in the difference in treatment efficacy in the glucocorticoid groups. Also, the drug was given neat in Shakeel 2012, but anaesthetic drug (parenteral lidocaine 1%, 10 mg/mL) was added to the glucocorticoid or NSAID in Leow 2018. No study has been conducted to evaluate the efficacy of the drug given neat versus the drug given in combination. However, the literature has recommended mixing anaesthetic drug with glucocorticoid for trigger finger injection (Kale 2017). The type of NSAID used was different in the two studies. Shakeel 2012 used diclofenac sodium, and Leow 2018 used ketorolac trometamol. A previous systematic review on the use of NSAID for osteoarthritis found that dose and type of NSAID used could affect treatment efficacy (da Costa 2017), and a review on low back pain found no differences in efficacy between various NSAIDs (Roelofs PDDM 2008). Thus, it is not conclusively known whether the efficacy of NSAIDs for trigger finger depends on the type of NSAID used.
We found no RCT evidence on the possible effectiveness of a wider range of NSAIDs including COX‐2‐selective ones, administered by oral and topical routes, at higher doses, in combination with anaesthetic drugs (da Costa 2017; Kale 2017; Roelofs PDDM 2008), and we found no evidence of comparisons against a wider range of glucocorticoid, non‐injection routes of delivery or against placebo. Applicability to patients with diabetes is very uncertain. Although about 39% of participants in Shakeel 2012 were diabetic, the reported analysis was not relevant, as it showed how intervention modified the effect of diabetes on symptom severity (see Table 4 of Shakeel 2012), instead of how diabetes modified the effect of intervention on symptom severity.
We suggest that a non‐inferiority analysis perspective may be more relevant when NSAIDs are compared with glucocorticoid treatment, as it is conceivable that the patient and the clinician would be willing to accept some NSAID treatment inferiority in exchange for the benefit of reduced risk of glucocorticoid adverse reactions. If so, this requires an a priori specification of a "non‐inferiority margin", which represents the maximum NSAID treatment inferiority that would be acceptable. However, logic dictates that the non‐inferiority margin should not exceed the inferiority of placebo as assessed in placebo‐controlled trials of glucocorticoid.
An even more crucial consideration is that analysis of just recurring symptoms may not provide a clinically meaningful measure of treatment effectiveness, as it is only one of two possible treatment failure events. The other event that is ignored is failure due to sustained symptom non‐responsiveness (without transient symptom resolution), and this happens to be the dominant failure mode in these two studies (Table 3). Ignoring this other failure event can lead to misleading conclusions about treatment efficacy, as is the case here. A more sensible analysis would combine both types of treatment failure. A sensitivity analysis shows that the treatment effect estimated from only recurrence failures is markedly different in magnitude and direction from that estimated from both types of failure (34% lower risk of failure versus 5% higher risk of failure; Analysis 7.1) and therefore is potentially seriously misleading.
| Study | Intervention group | Recurrence failure events | Sustained failure events |
| NSAID | 0 | 47 | |
| Steroid | 15 | 34 | |
| Total failure | 15 | 81 | |
| NSAID | 1 | 26 | |
| Steroid | 9 | 11 | |
| Total failure | 10 | 37 |
NSAID: non‐steroidal anti‐inflammatory drug.
Quality of the evidence
We assessed the quality of evidence for each outcome at the individual study level (risk of bias) and at the pooled data level (certainty of evidence).
Of the eight risk of bias (RoB) domains, Leow 2018 showed high risk of bias due to incompleteness of outcome data and unclear risk of bias for performance bias regarding blinding of participants and study personnel; the remaining six domains were at low risk of bias. Shakeel 2012 showed high risk of bias for allocation concealment and incompleteness of outcome data and unclear risk of bias for random sequence generation, blinding of participants and study personnel (performance bias), and other biases (non‐reporting of funding); the remaining three domains were at low risk of bias.
We found low‐certainty evidence for five (resolution, moderate to severe symptoms, total active motion, residual pain, and participant satisfaction) of the seven outcomes. We downgraded the evidence for risk of bias and imprecision. We found very low‐certainty evidence for symptom recurrence, as the risk of bias was judged very serious and the estimate imprecise. We found very low‐certainty evidence for adverse events, downgraded twice for imprecision, as data were derived from only one study and very few events were reported.
We are unable to comment on the clinical significance of a difference of 5 degrees lost in total active motion. This may be due to slight variability during measurements, and participants may not have any deficits in function.
Potential biases in the review process
Two authors of this review are the authors of one of the studies included in this review (Leow 2018). We resolved this potential bias by having Renea Johnston from the Cochrane Musculoskeletal Group and independent methodologist ECSY assess the risk of bias, and by involving two methodologists (ECSY, QZ) in all critical steps (Contributions of authors).
Agreements and disagreements with other studies or reviews
No other published review has considered NSAIDs for trigger finger. No prospective studies have examined the efficacy of topical or oral NSAIDs and glucocorticoids. We summarise the findings of a Cochrane Review synthesising the evidence for glucocorticoid injection for trigger finger (Peters‐Veluthamaningal 2009). These review authors found only two pseudo‐randomised studies (63 participants), both of which reported the dichotomous outcome "treatment success" (resolved, asymptomatic, or sufficiently improved to justify no further treatment), with maximum follow‐up of 1 month and 4 months. Corticosteroid injection with lidocaine was more effective than lidocaine alone for treatment success at 4 weeks (risk ratio 3.15, 95% confidence interval (CI) 1.34 to 7.40). The number needed to treat for an additional beneficial outcome was 3. No adverse events or side effects were reported. The findings from this review cannot be compared to the results of our review due to differences in interventions. We do not have another published review on NSAIDs for trigger finger against which to compare the findings of the present review.
Study flow diagram.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: NSAID injection vs steroid injection, Outcome 1: Resolution at 12 to 24 weeks
Comparison 1: NSAID injection vs steroid injection, Outcome 2: Moderate to severe disease at 12 to 24 weeks
Comparison 1: NSAID injection vs steroid injection, Outcome 3: Recurrence at 12 to 24 weeks
Comparison 1: NSAID injection vs steroid injection, Outcome 4: Total active motion
Comparison 1: NSAID injection vs steroid injection, Outcome 5: Pain
Comparison 1: NSAID injection vs steroid injection, Outcome 6: Satisfaction
Comparison 1: NSAID injection vs steroid injection, Outcome 7: Adverse events
Comparison 2: Sensitivity analysis (ITT scenarios), Outcome 1: Resolution at 12 to 24 weeks (ITT scenarios)
Comparison 2: Sensitivity analysis (ITT scenarios), Outcome 2: Moderate to severe disease at 12 to 24 weeks (ITT scenarios)
Comparison 2: Sensitivity analysis (ITT scenarios), Outcome 3: Recurrence at 12 to 24 weeks (ITT scenarios)
Comparison 2: Sensitivity analysis (ITT scenarios), Outcome 4: Pain (ITT scenarios)
Comparison 2: Sensitivity analysis (ITT scenarios), Outcome 5: Satisfaction (ITT scenarios)
Comparison 2: Sensitivity analysis (ITT scenarios), Outcome 6: Adverse events (ITT scenarios)
Comparison 3: Sensitivity analysis (12/24‐week follow‐up), Outcome 1: Resolution
Comparison 3: Sensitivity analysis (12/24‐week follow‐up), Outcome 2: Moderate to severe disease
Comparison 4: Sensitivity analysis for the recurrence outcome, Outcome 1: Recurrence (scenarios)
Comparison 5: Sensitivity analysis for the pain outcome, Outcome 1: Pain (scenarios)
Comparison 6: Sensitivity analysis for the adverse events outcome, Outcome 1: Adverse events (scenarios)
Comparison 7: Sensitivity analysis (treatment failure), Outcome 1: Types of treatment failure (unresolved symptoms)
| NSAID injection compared to glucocorticoid injection for trigger finger | ||||||
| Patient or population: adults (> 18 years of age) with trigger finger | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | №. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with glucocorticoid injection | Risk with NSAID injection | |||||
| Resolution at 12 to 24 weeks Quinell Grade (range 0 to 4, resolved disease is grade 0) | 41 per 100 | 34 per 100 (25.4 to 45.5) | RR 0.83 | 231 | ⊕⊕⊝⊝ | NSAID injection may have little to no effect on resolution of symptoms Absolute difference 7% lower (16% lower to 5% higher),c risk ratio 17% lower (38% lower to 11% higher) |
| Persistent moderate to severe symptoms at 12 to 24 weeks | 14 per 100 | 28 per 100 (16.3 to 47.3) | RR 2.03 | 231 | ⊕⊕⊝⊝ | NSAID injection may result in more people with persistent moderate to severe symptoms Absolute difference 14% higher (2% higher to 33% higher), risk ratio 103% higher (19% higher to 246% higher) NNTH 7, 95% CI 3 to 38 |
| Recurrence at 12 to 24 weeks | 21 per 100 | 1 per 100 (0.2 to 7.8) | RR 0.07 | 231 | ⊕⊝⊝⊝ | It is uncertain if NSAID injection results in fewer people with recurrence of symptoms Absolute difference 20% lower (21% to 13% lower), risk ratio 93% lower (99% lower to 62% lower) NNTB 6, 95% CI 5 to 8 |
| Total active motion | Mean total active motion was 240 degrees | Mean total active motion was 5 degrees lower (34.54 degrees lower to 24.54 degrees higher) | ‐ | 99 | ⊕⊕⊝⊝ | NSAID injection may have little to no effect on total active motion Absolute difference 5% lower (34.54% lower to 24.54% higher), risk ratio 2.1% lower (14.8% lower to 10.2% higher) |
| Residual pain | 24 per 100 | 20 per 100 (12.9 to 31.4) | RR 0.84 | 231 | ⊕⊕⊝⊝ | NSAID injection may have little to no effect on residual pain Absolute difference 4% lower (11% lower to 7% higher), risk ratio 16% lower (46% lower to 31% higher) |
| Participant‐reported treatment success | 68 per 100 | 64 per 100 (50.1 to 83.3) | RR 0.95 | 121 | ⊕⊕⊝⊝ | NSAID injection may have little to no effect on treatment success Absolute difference 4% lower (18% lower to 15% higher), risk ratio 5% lower (26% lower to 23% higher) |
| Adverse events | 1 per 100 | 1 per 100h | RR 2.00 | 231 | ⊕⊕⊝⊝ | It is uncertain if NSAID injection results in fewer adverse events Absolute difference 0% (2% lower to 3% higher), risk ratio 0% (200% lower to 300% higher) |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group (steroid injection) and the relative effect of the intervention (and its 95% CI). The exception is the adverse events outcome, for which the absolute effect of the intervention is used (see Footnote 9). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| aDowngraded by one level for risk of bias (high risk of selection and attrition bias). bDowngraded by one level for imprecision (95% CI supports both superiority for steroid injections and weak superiority for NSAID injections). cWith the exception of the adverse events outcome (see Footnote 10),the absolute effect is the simple difference between NSAID and steroid group risks in columns three and two of the table. dDowngraded by one level for imprecision (95% CI supports both superiority for steroid injection and no important difference between the two interventions). eDowngraded by two levels for risk of bias (high risk of selection and attrition bias; magnitude and precision of the pooled effect are highly sensitive to inclusion/exclusion of participants not at risk of recurrence; see Analysis 4.1). fDowngraded by one level for imprecision (95% CI supports substantial or weak superiority for NSAID injections). gDowngraded by one level for imprecision (95% CI supports superiority for steroid and NSAID injections). hThe risk in the intervention group was based on the pooled risk ratio because this effect uses data from both studies (Analysis 1.7), unlike the relative effect (see footnote below). iThis risk ratio estimate is based on only one study (Shakeel 2012), as the risk ratio of the excluded study ‐ Leow 2018 ‐ was not estimable due to zero adverse events in both treatment groups. jDowngraded by two levels for imprecision (data from only one study ‐ Shakeel 2012 ‐ and very few events). | ||||||
| ITT scenarios | Dropouts assumed to have the good outcome | |
| NSAID group | Steroid group | |
| Best case (for NSAID) | yes | no |
| Middle case 1 | no | no |
| Middle case 2 | yes | yes |
| Worst case (for NSAID) | no | yes |
| ITT: intention‐to‐treat. NSAID: non‐steroidal anti‐inflammatory drug. | ||
| ITT scenarios | Dropouts assumed to have the bad outcome | |
| NSAID group | Steroid group | |
| Best case (for NSAID) | no | yes |
| Middle case 1 | no | no |
| Middle case 2 | yes | yes |
| Worst case (for NSAID) | yes | no |
| ITT: intention‐to‐treat. NSAID: non‐steroidal anti‐inflammatory drug. | ||
| Study | Intervention group | Recurrence failure events | Sustained failure events |
| NSAID | 0 | 47 | |
| Steroid | 15 | 34 | |
| Total failure | 15 | 81 | |
| NSAID | 1 | 26 | |
| Steroid | 9 | 11 | |
| Total failure | 10 | 37 | |
| NSAID: non‐steroidal anti‐inflammatory drug. | |||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Resolution at 12 to 24 weeks Show forest plot | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.62, 1.11] |
| 1.2 Moderate to severe disease at 12 to 24 weeks Show forest plot | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 2.03 [1.19, 3.46] |
| 1.3 Recurrence at 12 to 24 weeks Show forest plot | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.07 [0.01, 0.38] |
| 1.4 Total active motion Show forest plot | 1 | 99 | Mean Difference (IV, Random, 95% CI) | ‐5.00 [‐34.54, 24.54] |
| 1.5 Pain Show forest plot | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.84 [0.54, 1.31] |
| 1.6 Satisfaction Show forest plot | 1 | 121 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.74, 1.23] |
| 1.7 Adverse events Show forest plot | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 2.00 [0.19, 21.42] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Resolution at 12 to 24 weeks (ITT scenarios) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1.1 Best case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 1.30 [0.62, 2.73] |
| 2.1.2 Middle case 1 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.62, 1.11] |
| 2.1.3 Middle case 2 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.90 [0.69, 1.18] |
| 2.1.4 Worst case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.67 [0.51, 0.87] |
| 2.1.5 Per‐protocol | 2 | 199 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.63, 1.10] |
| 2.2 Moderate to severe disease at 12 to 24 weeks (ITT scenarios) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.2.1 Best case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.70, 1.60] |
| 2.2.2 Middle case 1 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 2.03 [1.19, 3.46] |
| 2.2.3 Middle case 2 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 1.62 [1.14, 2.31] |
| 2.2.4 Worst case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 3.11 [1.91, 5.07] |
| 2.2.5 Per‐protocol | 2 | 199 | Risk Ratio (M‐H, Random, 95% CI) | 2.10 [1.25, 3.52] |
| 2.3 Recurrence at 12 to 24 weeks (ITT scenarios) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.3.1 Best case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.05 [0.01, 0.24] |
| 2.3.2 Middle case 1 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.07 [0.01, 0.38] |
| 2.3.3 Middle case 2 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.48 [0.29, 0.78] |
| 2.3.4 Worst case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.78 [0.45, 1.35] |
| 2.3.5 Per‐protocol | 2 | 199 | Risk Ratio (M‐H, Random, 95% CI) | 0.07 [0.01, 0.39] |
| 2.4 Pain (ITT scenarios) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.4.1 Best case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.39, 0.85] |
| 2.4.2 Middle case 1 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.84 [0.54, 1.31] |
| 2.4.3 Middle case 2 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.71, 1.28] |
| 2.4.4 Worst case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 2.26 [0.43, 11.86] |
| 2.4.5 Per‐protocol | 2 | 199 | Risk Ratio (M‐H, Random, 95% CI) | 0.88 [0.59, 1.32] |
| 2.5 Satisfaction (ITT scenarios) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.5.1 Best case | 1 | 121 | Risk Ratio (M‐H, Random, 95% CI) | 1.25 [1.02, 1.53] |
| 2.5.2 Middle case 1 | 1 | 121 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.74, 1.23] |
| 2.5.3 Middle case 2 | 1 | 121 | Risk Ratio (M‐H, Random, 95% CI) | 1.01 [0.87, 1.18] |
| 2.5.4 Worst case | 1 | 121 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.62, 0.96] |
| 2.5.5 Per‐protocol | 1 | 99 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.83, 1.21] |
| 2.6 Adverse events (ITT scenarios) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.6.1 Best case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.12 [0.01, 1.90] |
| 2.6.2 Middle case 1 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 2.00 [0.19, 21.42] |
| 2.6.3 Middle case 2 | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.45, 1.32] |
| 2.6.4 Worst case | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 11.13 [2.11, 58.60] |
| 2.6.5 Per‐protocol | 2 | 199 | Risk Ratio (M‐H, Random, 95% CI) | 2.00 [0.19, 21.36] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Resolution Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 3.1.1 Longest follow‐up time | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.62, 1.11] |
| 3.1.2 Up to 12‐week follow‐up | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.32 [0.03, 3.03] |
| 3.2 Moderate to severe disease Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 3.2.1 Longest follow‐up time | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 2.03 [1.19, 3.46] |
| 3.2.2 Up to 12‐week follow‐up | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 3.20 [1.71, 5.98] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Recurrence (scenarios) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 4.1.1 Only those at risk of recurrence | 2 | 113 | Risk Ratio (M‐H, Random, 95% CI) | 0.13 [0.02, 0.63] |
| 4.1.2 All randomised | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.07 [0.01, 0.38] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Pain (scenarios) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 5.1.1 Include continuous pain | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.84 [0.54, 1.31] |
| 5.1.2 Exclude continuous pain | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 0.82 [0.52, 1.28] |
| 5.1.3 Painful Grade 2 disease | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 1.36 [0.41, 4.52] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Adverse events (scenarios) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 6.1.1 Continuous pain is not an AE | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 6.1.2 Continuous pain is an AE | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 2.00 [0.19, 21.42] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Types of treatment failure (unresolved symptoms) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 7.1.1 Recurrence failure (only those at risk) | 2 | 113 | Risk Ratio (M‐H, Random, 95% CI) | 0.13 [0.02, 0.63] |
| 7.1.2 All cases of unresolved symptom failure | 2 | 231 | Risk Ratio (M‐H, Random, 95% CI) | 1.10 [0.82, 1.48] |
