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Abstract Number: 946

Comparative Effectiveness of Second-Line Treatment Strategies for Lyme Arthritis in Children

Daniel B. Horton1, Alysha J. Taxter2, Brandt Groh3, David D. Sherry4 and Carlos D. Rosé5, 1Pediatrics, Division of Pediatric Rheumatology, Rutgers Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences, New Brunswick, NJ, 2Pediatrics, Brenner Children's Hospital, Wake Forest Baptist Medical Center, Winston-Salem, NC, 3Pediatrics, Penn State Milton S. Hershey Medical Center, Hershey, PA, 4Pediatrics, Children's Hospital of Philadelphia, Division of Pediatric Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 5Pediatrics, Division of Rheumatology, Nemours/A.I. duPont Hospital for Children, Thomas Jefferson University, Wilmington, DE

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Comparative effectiveness and harms, glucocorticoids and pediatric rheumatology, Lyme disease

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Session Information

Date: Sunday, November 13, 2016

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects I: Juvenile Arthritis

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:  First-line treatment for Lyme arthritis is fairly standardized, but second-line strategies are more variable. We compared the effectiveness of oral antibiotics, intra-articular glucocorticoid injections (IAGC), and intravenous (IV) antibiotics in second-line regimens for pediatric Lyme arthritis.

Methods: We performed a retrospective cohort study of children age ≤18 seen in 3 pediatric rheumatology clinics for Western blot-confirmed Lyme arthritis. We limited the cohort to children who began second-line therapy ≤4 months after starting antibiotics, a timeline consistent with usual practice at these sites. Second-line strategies were: 1) a second course of oral antibiotics alone, 2) IAGC with or without oral antibiotics, or 3) a course of IV antibiotics. The primary outcome was development of antibiotic-refractory Lyme arthritis (ARLA), defined as persistent arthritis ≥2 months after completing ≥56 days of oral antibiotics or ≥14 days of IV antibiotics, per IDSA/Red Book guidelines. The secondary outcome was rate of clinical resolution of arthritis. We compared second-line treatment strategies using logistic regression for ARLA and Cox regression for rate of resolution, adjusted for confounders.

Results: There were 129 children with second-line treatment for Lyme arthritis, of whom 42 (33%) developed ARLA: 29/83 (35%) on oral antibiotics alone; 3/18 (17%) with IAGC ± oral antibiotics; and 10/28 (36%) after IV antibiotics. Children who received second-line IAGC or IV antibiotics were more likely female (Table 1). Children whose arthritis markedly worsened after antibiotic initiation were more likely to receive second-line IV antibiotics (P<0.01). After adjusting for sex and worsening arthritis, children who received IAGC ± oral antibiotics appeared to have a decreased risk of developing ARLA compared with children receiving second-line oral antibiotics alone, but this did not meet traditional levels of significance (aOR 0.4, 95% CI 0.1, 1.4, P = 0.14) (Table 2). Similarly, second-line IAGC was associated with non-significantly increased rates of resolution of arthritis (aHR 1.6, 95% CI 0.9, 2.9, P = 0.11). There was no significant difference in the risk of developing ARLA (P=0.55) or rate of resolution (P=0.46) between groups receiving second-line IV or oral antibiotics (Table 2). Results were similar after excluding children whose disease worsened after antibiotic initiation.

Conclusion: Use of second-line intra-articular glucocorticoid injection may hasten the resolution of Lyme arthritis and prevent chronic Lyme arthritis in children. Further study of this strategy in larger cohorts is warranted.

Table 1. Clinical and treatment characteristics of children who received second-line treatment for Lyme arthritis
Characteristic

(1) Oral antibiotics alone (N=83)

(2) IAGC ± oral antibiotics (N=18)

P-value

(2) vs. (1)

(3) IV antibiotics (N=28)

P-value

(3) vs. (1)

Age in years, median (IQR)

12.1 (9.4, 14.5)

11.2 (8.3, 13.7)

0.38

12.2 (10.2, 14.2)

0.77

Male sex, N (%)

64 (77)

10 (56)

0.06

15 (54)

0.02

Duration of initial joint symptoms in days, median (IQR)

7 (4, 28)

3 (3, 21)

0.26

14 (7, 28)

0.36

More than 1 joint involved,1 N (%)

12 (14)

3 (17)

0.81

5 (18)

0.67

Non-knee joint involved, N (%)

11 (13)

2 (11)

0.81

2 (7)

0.39

Marked clinical worsening ≤6 weeks after antibiotic initiation,2 N (%)

10 (12)

0

0.12

10 (36)

<0.01

First antibiotic course ≥28 days in duration, N (%)

55 (66)

11 (61)

0.68

19 (68)

0.88

First antibiotic course dose correct per guidelines, N (%)

58 (70)

12 (67)

0.79

22 (79)

0.38

Second-line antibiotics, N (%)

<0.01

<0.01

Doxycycline

61 (73)

10 (56)

0

Amoxicillin

17 (20)

3 (17)

0

Cefuroxime

4 (5)

1 (6)

0

Other oral antibiotic

1 (1)

0

0

Ceftriaxone

0

0

28 (100)

None

0

4 (22)

0

IAGC, intra-articular glucocorticoid injection; IQR, interquartile range; IV, intravenous. 1 Two knees would count as two joints 2 New massive effusion, joint capsule rupture, or joint recruitment

Table 2. Multivariable analysis comparing second-line regimens for pediatric Lyme arthritis

Risk of developing antibiotic-refractory Lyme arthritis

Rate of clinical resolution of arthritis1

Treatment strategy

aOR2 (95% CI)

P-value

aHR2 (95% CI)

P-value

Oral antibiotics alone (reference)

1.0

–

1.0

–

IAGC ± oral antibiotics

0.4 (0.1, 1.4)

0.14

1.6 (0.9, 2.9)

0.11

IV antibiotics

0.7 (0.3, 2.0)

0.55

1.2 (0.7, 2.1)

0.46

aHR, adjusted hazard ratio; aOR, adjusted odds ratio; CI, confidence interval; IAGC, intra-articular glucocorticoid injection; IV, intravenous. 1Presence of mild, asymptomatic joint swelling was considered compatible with clinical resolution if there was no subsequent worsening or recurrence of symptomatic arthritis 2 Multivariable models also adjusted for male sex and marked worsening on antibiotics, defined as a new massive effusion, joint capsule rupture, or joint recruitment within 6 weeks of antibiotic initiation

Disclosure: D. B. Horton, None; A. J. Taxter, None; B. Groh, None; D. D. Sherry, None; C. D. Rosé, None.

To cite this abstract in AMA style:

Horton DB, Taxter AJ, Groh B, Sherry DD, Rosé CD. Comparative Effectiveness of Second-Line Treatment Strategies for Lyme Arthritis in Children [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/comparative-effectiveness-of-second-line-treatment-strategies-for-lyme-arthritis-in-children/. Accessed .
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