Hydroxychloroquine and Colchicine in Hand Osteoarthritis at the 2020 EULAR Online Meeting

Hydroxychloroquine and colchicine in hand osteoarthritis isn't so far from the main stream of medicine. Hydroxychloroquine is important in the treatment of systemic lupus erythematodes. The current president of the U.S.A. has been advocating hydroxchloquine to fight covid-19 disease, though lacking scientific support. For colchicine there have been studies concerning osteoarthritis of weight bearing joints, mostly knee osteoarthritis.

For hydroxychloroquine and colchicine in hand osteoarthritis there have been two studies at the 2020 EULAR Online Meeting.

But let me start with a study by L.R Bryant and colleagues in 1995 [1]: „Hydroxychloroquine in the Treatment of Erosive Osteoarthritis“. The study had been underpowered (N=8). The authors concluded: „The use of hydroxychloroquine in patients with erosive OA unresponsive to NSAID appears promising. Prospective studies are needed to confirm our observations.“

C. Kedor and colleagues presented [2] at the 2020 EULAR Online Meeting: „OP0186 HYDROXYCHLOROQUINE IN PATIENTS WITH INFLAMMATORY AND EROSIVE OSTEOARTHRITIS OF THE HANDS: RESULTS OF A RANDOMIZED, DOUBLEBLIND, PLACEBO CONTROLLED, MULTI-CENTRE, INVESTIGATOR-INITIATED TRIAL (OA TREAT)“. The study originated in 2014. „The primary endpoint was AUSCAN for pain and hand disability at week 52 (W52). A secondary endpoint was radiographic progression from baseline (BL) to W52.“ „Of 156 patients 3 were excluded and 75 were randomized to HCQ and 78 to PBO.“ With only morning stiffness having been significantly reduced in the HCQ group, the authors had to conclude: „HCQ was no more effective than PBO for changes in pain, function and radiographic scores in the 52-week period.“

The study is congruent with a study that originated in 2013 and had been published earlier [3]: „Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A Randomized Trial“. „The primary end point was average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months.“ The authors concluded: „Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis.“

So we now have two large randomized studies showing that hydroxychloroquine is ineffective in hand osteoarthritis.

C. Davis and colleagues presented [4]: „FRI0399 COLCHICINE IS NOT EFFECTIVE FOR REDUCING OSTEOARTHRITIC HAND PAIN COMPARED TO PLACEBO: A RANDOMISED, PLACEBO-CONTROLLED TRIAL (COLAH)“. Colchicine is effective as an anti-inflammatory agent in gouty arthritis, but has not been investigated before in hand osteoarthritis. The authors could evaluate 58 participants, who completed the study (N=27 colchicine, N=31 placebo). The authors concluded: „Colchicine 1mg daily for 12 weeks was not effective in improving pain, tender and swollen joint count or grip strength in symptomatic hand osteoarthritis patients. This study does not support colchicine for treatment of symptoms of hand osteoarthritis.“

It would have been nice to have drugs to prevent progression and treat symptoms of hand osteoarhritis, but hydroxychloroquine and colchicine are ineffective and should not be prescribed in patients with (erosive) hand osteoarthritis.

Links and References:

[1] Bryant LR, des Rosier KF, Carpenter MT. Hydroxychloroquine in the treatment of erosive osteoarthritis. J Rheumatol. 1995;22(8):1527-1531.

[2] C. Kedor1, J. Detert2, R. Rau3, S. Wassenberg3, J. Listing4, P. Klaus5, T. Braun1, W. Hermann6, S. Weiner7, M. Bohl-Buhler8, F. Buttgereit1, G. R. Burmester1. OP0186 HYDROXYCHLOROQUINE IN PATIENTS WITH INFLAMMATORY AND EROSIVE OSTEOARTHRITIS OF THE HANDS: RESULTS OF A RANDOMIZED, DOUBLEBLIND,

PLACEBO CONTROLLED, MULTI-CENTRE, INVESTIGATOR-INITIATED TRIAL (OA TREAT). DOI: 10.1136/annrheumdis-2020-eular.819

[3] Kingsbury SR, Tharmanathan P, Keding A, et al. Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A Randomized Trial. Ann Intern Med. 2018;168(6):385-395. doi:10.7326/M17-1430

[4] C. Davis1,2, C. Ruediger1,2, K. Dyer2, S. Lester1,2, S. Graf3, F. P. B. Kroon4, S. Whittle2, C. Hill1,2. FRI0399 COLCHICINE IS NOT EFFECTIVE FOR REDUCING OSTEOARTHRITIC HAND PAIN COMPARED TO PLACEBO: A RANDOMISED, PLACEBO-CONTROLLED TRIAL (COLAH). DOI: 10.1136/annrheumdis-2020-eular.4040

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Risk Reduction of Retinopathy in the Therapy with Chloroquine and Hydroxychloroquine in Rheumatology

Chloroquine (CQ) has been developed for the therapy of malaria. It’s an old drug as the substance had already been discovered in 1934. You might know hydroxychloroquine (HCQ) Plaquenil or Quensyl, which differs from chloroquine just by the presence of a hydroxyl group. We use these antimalarials in rheumatology as DMARD (Disease Modifying Anti Rheumatic Drugs) to treat rheumatoid arthritis (often in combination with methotrexate), systemic lupus erythematodes (SLE), Sjoegren’s syndrome, and others. A study in 1985 found a lower rate of retinopathy in hydroxychloroquine when compared to chloroquine. As retinopathy is not reversible and as there is no present therapy, we need to reduce the risk for the development of antimalarial associated retinopathy.

In June 2016 the American Academy of Ophthalmology published recommendations on screening for chloroquine and hydroxychloroquine retinopathy. They recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight. “The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years.” Higher dosage means higher risk, so we have to keep the daily dosage down. Long duration of therapy with antimalarials is another significant risk factor, so we must try to reduce the duration of this therapy. This might be hard to achieve in lupus. Renal disease is another risk factor to look for, but rheumatologists usually screen their patients for renal disease. And we have to look for tamoxifen, as this drug increases the risk for chloroquine and hydroxychloroquine retinopathy. This is sad to hear as the group of patients needing tamoxifen is also the group, where other therapy options like biologicals are contraindicated.

Risk Reduction of Retinopathy:

·         adapted dosage of CQ and HCQ

·         avoiding long duration of therapy

·         screening for renal disease

·         monitoring concomitant medication

·         screening for retinopathy

Links:

https://en.wikipedia.org/wiki/Chloroquine

https://en.wikipedia.org/wiki/Hydroxychloroquine

https://www.ncbi.nlm.nih.gov/pubmed/4057189

https://www.ncbi.nlm.nih.gov/pubmed?term=26992838

Handosteoarthritis and DMARDs at the EULAR Annual Meeting 2015 in Rome PLUS

At the EULAR Annual Meeting 2015 in Rome I’ve seen two abstracts / posters on osteoarthritis and DMARDs, actually both abstracts looked at hydroxychloroquine (HCQ)

N. Cid Boza and colleagues published [AB0865]: “Hydroxychloroquine in the symptomatic control of erosive hand osteoarthritis”. “A total of 10 patients were included between July 2012 and July 2013 and all completed a 24 weeks follow up.” “A 50% of patients reached a reduction of at least 20% of pain assessment by AUSCAN pain domain …”. They concluded: “Our results suggest that hydroxychloroquine may decrease inflammatory activity in erosive hands OA and thus functional impairment after 24 weeks … Hydroxychloroquine was well tolerated and no major side effects were observed.”

N=10 isn’t much to draw conclusions upon! It is unclear, how “inflammatory activity” has been measured. All in all, I cannot see any advantage of hydroxychloroquine over non-treatment. No major side effects in 10 patients is underrating the known risks of the drug.

N. Basoski and colleagues looked at [OP0304]: “Efficacy of hydroxychloroquine in primary hand osteoarthritis: a randomized, double-blind, placebo controlled trial.” They concluded: “This study shows that 24 weeks of treatment with HCQ in symptomatic hand OA did not reduce pain when compared to placebo. Also, no effect was observed in change of AUSCAN total and subscales scores or AIMS2-SF scores between both treatment groups. These results suggest that HCQ should not be prescribed in patients with primary hand OA with mild to moderate pain symptoms.”

Well, this study had been designed double-blind, placebo controlled, and was with N=98 in both groups well powered. The authors didn’t want to rule out that HCQ could be useful in other phenotypes of hand OA.

Not let’s come to the PLUS …

Today I’ve received the September issue of Annals of rheumatic diseases. X. Chevalier and colleagues published: Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicenter, double-blind, placebo-controlled trial.” [Chevalier, X, et al. Ann Rheum Dis 2015;74: 1697-1705. doi:10.1136/annrheumdis-2014-205348] The authors concluded that “Adalimumab was not superior to placebo to alleviate pain in patients with hand OA not responding to analgesics and NSAIDs.”

We might conclude that DMARDs that are effective in rheumatoid arthritis and/or psoriatic arthritis might not work in osteoarthritis, even if joint destruction in the end might look similar. We might go on testing other traditional or biological DMARDs, but my guess is that it’s a dead end.

We should put the focus on studying how the process of joint degradation is started, maintained, and timed in osteoarthritis, before we look, which drug may have a chance to counteract this process.